Package 'qtl'

Title: Tools for Analyzing QTL Experiments
Description: Analysis of experimental crosses to identify genes (called quantitative trait loci, QTLs) contributing to variation in quantitative traits. Broman et al. (2003) <doi:10.1093/bioinformatics/btg112>.
Authors: Karl W Broman [aut, cre] , Hao Wu [aut], Gary Churchill [ctb] , Saunak Sen [ctb] , Danny Arends [ctb] , Robert Corty [ctb], Timothee Flutre [ctb], Ritsert Jansen [ctb], Pjotr Prins [ctb] , Lars Ronnegard [ctb], Rohan Shah [ctb], Laura Shannon [ctb], Quoc Tran [ctb], Aaron Wolen [ctb], Brian Yandell [ctb] , R Core Team [ctb]
Maintainer: Karl W Broman <[email protected]>
License: GPL-3
Version: 1.70
Built: 2024-11-01 11:31:27 UTC
Source: CRAN

Help Index


Introductory comments on R/qtl

Description

A brief introduction to the R/qtl package, with a walk-through of an analysis.

New to R and/or R/qtl?

  • In order to use the R/qtl package, you must type (within R) library(qtl). You may wish to include this in a .Rprofile file.

  • Documention and several tutorials are available at the R archive (https://cran.r-project.org).

  • Use the help.start function to start the html version of the R help.

  • Type library(help=qtl) to get a list of the functions in R/qtl.

  • Use the example function to run examples of the various functions in R/qtl.

  • A tutorial on the use of R/qtl is distributed with the package and is also available at https://rqtl.org/rqtltour.pdf.

  • Download the latest version of R/qtl from the R archive or from https://rqtl.org.

Walk-through of an analysis

Here we briefly describe the use of R/qtl to analyze an experimental cross. A more extensive tutorial on its use is distributed with the package and is also available at https://rqtl.org/rqtltour.pdf.

A difficult first step in the use of most data analysis software is the import of data. With R/qtl, one may import data in several different formats by use of the function read.cross. The internal data structure used by R/qtl is rather complicated, and is described in the help file for read.cross. We won't discuss data import any further here, except to say that the comma-delimited format ("csv") is recommended. If you have trouble importing data, send an email to Karl Broman, [email protected], perhaps attaching examples of your data files. (Such data will be kept confidential.) Also see the sample data files and code at https://rqtl.org/sampledata/.

We consider the example data hyper, an experiment on hypertension in the mouse, kindly provided by Bev Paigen and Gary Churchill. Use the data function to load the data.

data(hyper)

The hyper data set has class "cross". The function summary.cross gives summary information on the data, and checks the data for internal consistency. A number of other utility functions are available; hopefully these are self-explanatory.

summary(hyper)
nind(hyper)
nphe(hyper)
nchr(hyper)
nmar(hyper)
totmar(hyper)

The function plot.cross gives a graphical summary of the data; it calls plotMissing (to plot a matrix displaying missing genotypes) and plotMap (to plot the genetic maps), and also displays histograms or barplots of the phenotypes. The plotMissing function can plot individuals ordered by their phenotypes; you can see that for most markers, only individuals with extreme phenotypes were genotyped.

plot(hyper)
plotMissing(hyper)
plotMissing(hyper, reorder=TRUE)
plotMap(hyper)

Note that one marker (on chromosome 14) has no genotype data. The function drop.nullmarkers removes such markers from the data.

hyper <- drop.nullmarkers(hyper)
totmar(hyper)

The function est.rf estimates the recombination fraction between each pair of markers, and calculates a LOD score for the test of rr = 1/2. This is useful for identifying markers that are placed on the wrong chromosome. Note that since, for these data, many markers were typed only on recombinant individuals, the pairwise recombination fractions show rather odd patterns.

hyper <- est.rf(hyper)
plotRF(hyper)
plotRF(hyper, chr=c(1,4))

To re-estimate the genetic map for an experimental cross, use the function est.map. The function plotMap, in addition to plotting a single map, can plot the comparison of two genetic maps (as long as they are composed of the same numbers of chromosomes and markers per chromosome). The function replace.map map be used to replace the genetic map in a cross with a new one.

newmap <- est.map(hyper, error.prob=0.01, verbose=TRUE)
plotMap(hyper, newmap)
hyper <- replace.map(hyper, newmap)

The function calc.errorlod may be used to assist in identifying possible genotyping errors; it calculates the error LOD scores described by Lincoln and Lander (1992). The calc.errorlod function return a modified version of the input cross, with error LOD scores included. The function top.errorlod prints the genotypes with values above a cutoff (by default, the cutoff is 4.0).

hyper <- calc.errorlod(hyper, error.prob=0.01)
top.errorlod(hyper)

The function plotGeno may be used to inspect the observed genotypes for a chromosome, with likely genotyping errors flagged.

plotGeno(hyper, chr=16, ind=c(24:34, 71:81))

Before doing QTL analyses, some intermediate calculations need to be performed. The function calc.genoprob calculates conditional genotype probabilities given the multipoint marker data. sim.geno simulates sequences of genotypes from their joint distribution, given the observed marker data.

As with calc.errorlod, these functions return a modified version of the input cross, with the intermediate calculations included. The step argument indicates the density of the grid on which the calculations will be performed, and determines the density at which LOD scores will be calculated.

hyper <- calc.genoprob(hyper, step=2.5, error.prob=0.01)
hyper <- sim.geno(hyper, step=2.5, n.draws=64, error.prob=0.01)

The function scanone performs a genome scan with a single QTL model. By default, it performs standard interval mapping (Lander and Botstein 1989): use of a normal model and the EM algorithm. If one specifies method="hk", Haley-Knott regression is performed (Haley and Knott 1992). These two methods require the results from calc.genoprob.

out.em <- scanone(hyper)
out.hk <- scanone(hyper, method="hk")

If one specifies method="imp", a genome scan is performed by the multiple imputation method of Sen and Churchill (2001). This method requires the results from sim.geno.

out.imp <- scanone(hyper, method="imp")

The output of scanone is a data.frame with class "scanone". The function plot.scanone may be used to plot the results, and may plot up to three sets of results against each other, as long as they conform appropriately.

plot(out.em)
plot(out.hk, col="blue", add=TRUE)
plot(out.imp, col="red", add=TRUE)
plot(out.hk, out.imp, out.em, chr=c(1,4), lty=1,
col=c("blue","red","black"))

The function summary.scanone may be used to list information on the peak LOD for each chromosome for which the LOD exceeds a specified threshold.

summary(out.em)
summary(out.em, threshold=3)
summary(out.hk, threshold=3)
summary(out.imp, threshold=3)

The function max.scanone returns the maximum LOD score, genome-wide.

max(out.em)
max(out.hk)
max(out.imp)

One may also use scanone to perform a permutation test to get a genome-wide LOD significance threshold.

operm.hk <- scanone(hyper, method="hk", n.perm=1000)

The result has class "scanoneperm". The summary.scanoneperm function may be used to calculate LOD thresholds.

summary(operm.hk, alpha=0.05)

The permutation results may also be used in the summary.scanone function to calculate LOD thresholds and genome-scan-adjusted p-values.

summary(out.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE)

We should say at this point that the function save.image will save your workspace to disk. You'll wish you had used this if R crashes.

save.image()

The function scantwo performs a two-dimensional genome scan with a two-QTL model. Methods "em", "hk" and "imp" are all available. scantwo is considerably slower than scanone, and can require a great deal of memory. Thus, you may wish to re-run calc.genoprob and/or sim.geno with a more coarse grid.

hyper <- calc.genoprob(hyper, step=10, err=0.01)
hyper <- sim.geno(hyper, step=10, n.draws=64, err=0.01)

out2.hk <- scantwo(hyper, method="hk")
out2.em <- scantwo(hyper)
out2.imp <- scantwo(hyper, method="imp")

The output is an object with class scantwo. The function plot.scantwo may be used to plot the results. The upper triangle contains LOD scores for tests of epistasis, while the lower triangle contains LOD scores for the full model.

plot(out2.hk)
plot(out2.em)
plot(out2.imp)

The function summary.scantwo lists the interesting aspects of the output. For each pair of chromosomes (k,l)(k,l), it calculates the maximum LOD score for the full model, Mf(k,l)M_f(k,l); a LOD score indicating evidence for a second QTL, allowing for epistasis), Mfv1(k,l)M_{fv1}(k,l); a LOD score indicating evidence for epistasis, Mi(k,l)M_i(k,l); the LOD score for the additive QTL model, Ma(k,l)M_a(k,l); and a LOD score indicating evidence for a second QTL, assuming no epistasis, Mav1(k,l)M_{av1}(k,l).

You must provide five LOD thresholds, corresponding to the above five LOD scores, and in that order. A chromosome pair is printed if either (a) Mf(k,l)TfM_f(k,l) \ge T_f and (Mfv1(k,l)Tfv1M_{fv1}(k,l) \ge T_{fv1} or Mi(k,l)TiM_i(k,l) \ge T_i), or (b) Ma(k,l)TaM_a(k,l) \ge T_a and Mav1(k,l)Tav1M_{av1}(k,l) \ge T_{av1}.

summary(out2.em, thresholds=c(6.2, 5.0, 4.6, 4.5, 2.3))
summary(out2.em, thresholds=c(6.2, 5.0, Inf, 4.5, 2.3))

In the latter case, the interaction LOD score will be ignored.

The function max.scantwo returns the maximum joint and additive LODs for a two-dimensional genome scan.

max(out2.em)

Permutation tests may also performed with scantwo; it may take a few days of CPU time. The output is a list containing the maxima of the above five LOD scores for each of the imputations.

operm2 <- scantwo(hyper, method="hk", n.perm=100)
summary(operm2, alpha=0.05)

Citing R/qtl

To cite R/qtl in publications, use the Broman et al. (2003) reference listed below.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W. and Sen, Ś. (2009) A guide to QTL mapping with R/qtl. Springer. https://rqtl.org/book/

Broman, K. W., Wu, H., Sen, Ś. and Churchill, G. A. (2003) R/qtl: QTL mapping in experimental crosses. Bioinformatics 19, 889–890.

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Lander, E. S. and Botstein, D. (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.

Lincoln, S. E. and Lander, E. S. (1992) Systematic detection of errors in genetic linkage data. Genomics 14, 604–610.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.


Indicate marker covariates from composite interval mapping

Description

Add dots at the locations of the selected marker covariates, for a plot of composite interval mapping results.

Usage

add.cim.covar(cimresult, chr, gap=25, ...)

Arguments

cimresult

Composite interval mapping results, as output from cim.

chr

Optional vector specifying which chromosomes to plot. (The chromosomes must be specified by name.) This should be identical to that used in the call to plot.scanone.

gap

Gap separating chromosomes (in cM). This should be identical to that used in the call to plot.scanone.

...

Additional plot arguments, passed to the function points.

Details

One must first have used the function plot.scanone to plot the composite interval mapping results.

The arguments chr and gap must be identical to the values used in the call to plot.scanone.

Dots indicating the locations of the selected marker covariates are displayed on the x-axis. (By default, solid red circles are plotted; this may be modified by specifying the graphics parameters pch and col.)

Value

A data frame indicating the marker covariates that were plotted.

Author(s)

Karl W Broman, [email protected]

See Also

cim, plot.scanone

Examples

## Not run: data(hyper)
hyper <- calc.genoprob(hyper, step=2.5)

out <- scanone(hyper)
out.cim <- cim(hyper, n.marcovar=3)
plot(out, out.cim, chr=c(1,4,6,15), col=c("blue", "red"))

add.cim.covar(out.cim, chr=c(1,4,6,15))
## End(Not run)

Add significance threshold to plot

Description

Add a significance threshold to a plot created by plot.scanone), using the permutation results.

Usage

add.threshold(out, chr, perms, alpha=0.05, lodcolumn=1, gap=25, ...)

Arguments

out

An object of class "scanone", as output by scanone. This must be identical to what was used in the call to plot.scanone.

chr

Optional vector specifying which chromosomes to plot. If a selected subset of chromosomes were plotted, they must be specified here.

perms

Permutation results from scanone, used to calculate the significance threshold.

alpha

Significance level of the threshold.

lodcolumn

An integer indicating which of column in the permutation results should be used.

gap

Gap separating chromosomes (in cM). This must be identical to what was used in the call to plot.scanone.

...

Passed to the function abline when it is called.

Details

This function allows you to add a horizontal line at the significance threshold to genome scan results plotted by plot.scanone.

The arguments out, chr, and gap must match what was used in the call to plot.scanone.

The argument perms must be specified. If X-chromosome-specific permutations were performed (via the argument perm.Xsp in the call to scanone), separate thresholds will be plotted for the autosomes and the X chromosome. These are calculated via the summary.scanoneperm function.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, plot.scanone, summary.scanoneperm, xaxisloc.scanone

Examples

data(hyper)
hyper <- calc.genoprob(hyper)
out <- scanone(hyper, method="hk")
operm <- scanone(hyper, method="hk", n.perm=100, perm.Xsp=TRUE)

plot(out, chr=c(1,4,6,15,"X"))
add.threshold(out, chr=c(1,4,6,15,"X"), perms=operm, alpha=0.05)
add.threshold(out, chr=c(1,4,6,15,"X"), perms=operm, alpha=0.1,
              col="green", lty=2)

Add QTL x covariate interaction to a multiple-QTL model

Description

Try adding all QTL x covariate interactions, one at a time, to a multiple QTL model, for a given set of covariates.

Usage

addcovarint(cross, pheno.col=1, qtl, covar=NULL, icovar, formula,
            method=c("imp","hk"), model=c("normal", "binary"),
            verbose=TRUE, pvalues=TRUE, simple=FALSE, tol=1e-4,
            maxit=1000, require.fullrank=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

An object of class qtl, as output from makeqtl.

covar

A matrix or data.frame of covariates. These must be strictly numeric.

icovar

Vector of character strings indicating the columns in covar to be considered for QTL x covariate interactions.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are referred to as Q1, Q2, etc. Covariates are referred to by their names in the data frame covar.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

verbose

If TRUE, will print a message if there are no interactions to test.

pvalues

If FALSE, p-values will not be included in the results.

simple

If TRUE, don't include p-values or sums of squares in the summary.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

require.fullrank

If TRUE, give LOD=0 when covariate matrix in the linear regression is not of full rank.

Details

The formula is used to specified the model to be fit. In the formula, use Q1, Q2, etc., or q1, q2, etc., to represent the QTLs, and the column names in the covariate data frame to represent the covariates.

We enforce a hierarchical structure on the model formula: if a QTL or covariate is in involved in an interaction, its main effect must also be included.

Value

An object of class addcovarint, with results as in the drop-one-term analysis from fitqtl. This is a data frame (given class "addcovarint", with the following columns: degrees of freedom (df), Type III sum of squares (Type III SS), LOD score(LOD), percentage of variance explained (%var), F statistics (F value), and P values for chi square (Pvalue(chi2)) and F distribution (Pvalue(F)).

Note that the degree of freedom, Type III sum of squares, the LOD score and the percentage of variance explained are the values comparing the full to the sub-model with the term dropped. Also note that for imputation method, the percentage of variance explained, the the F values and the P values are approximations calculated from the LOD score.

QTL x covariate interactions already included in the input formula are not tested.

Author(s)

Karl W Broman, [email protected]

References

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

addint, fitqtl, makeqtl, scanqtl, refineqtl, addqtl, addpair

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 8, 13)
qp <- c(26, 56, 28)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

# use the sex phenotype as the covariate
covar <- data.frame(sex=fake.f2$pheno$sex)

# try all possible QTL x sex interactions, one at a time
addcovarint(fake.f2, pheno.col=1, qtl, covar, "sex", y~Q1+Q2+Q3,
            method="hk")

Add pairwise interaction to a multiple-QTL model

Description

Try adding all possible pairwise interactions, one at a time, to a multiple QTL model.

Usage

addint(cross, pheno.col=1, qtl, covar=NULL, formula, method=c("imp","hk"),
       model=c("normal", "binary"), qtl.only=FALSE, verbose=TRUE,
       pvalues=TRUE, simple=FALSE, tol=1e-4, maxit=1000, require.fullrank=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix to be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

An object of class qtl, as output from makeqtl.

covar

A matrix or data.frame of covariates. These must be strictly numeric.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are referred to as Q1, Q2, etc. Covariates are referred to by their names in the data frame covar. If the new QTL is not included in the formula, its main effect is added.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

qtl.only

If TRUE, only test QTL:QTL interactions (and not interactions with covariates).

verbose

If TRUE, will print a message if there are no interactions to test.

pvalues

If FALSE, p-values will not be included in the results.

simple

If TRUE, don't include p-values or sums of squares in the summary.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

require.fullrank

If TRUE, give LOD=0 when covariate matrix in the linear regression is not of full rank.

Details

The formula is used to specified the model to be fit. In the formula, use Q1, Q2, etc., or q1, q2, etc., to represent the QTLs, and the column names in the covariate data frame to represent the covariates.

We enforce a hierarchical structure on the model formula: if a QTL or covariate is in involved in an interaction, its main effect must also be included.

Value

An object of class addint, with results as in the drop-one-term analysis from fitqtl. This is a data frame (given class "addint", with the following columns: degrees of freedom (df), Type III sum of squares (Type III SS), LOD score(LOD), percentage of variance explained (%var), F statistics (F value), and P values for chi square (Pvalue(chi2)) and F distribution (Pvalue(F)).

Note that the degree of freedom, Type III sum of squares, the LOD score and the percentage of variance explained are the values comparing the full to the sub-model with the term dropped. Also note that for imputation method, the percentage of variance explained, the the F values and the P values are approximations calculated from the LOD score.

Pairwise interactions already included in the input formula are not tested.

Author(s)

Karl W Broman, [email protected]

References

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

addcovarint, fitqtl, makeqtl, scanqtl, refineqtl, addqtl, addpair

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 8, 13)
qp <- c(26, 56, 28)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

# try all possible pairwise interactions, one at a time
addint(fake.f2, pheno.col=1, qtl, formula=y~Q1+Q2+Q3, method="hk")

Add phenotype location into a cross object

Description

Add phenotype location(s) into a cross object (with eQTL/pQTL studies)

Usage

addloctocross(cross, locations=NULL, locfile="locations.txt", verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

locations

R variable holding location information

locfile

load from a file, see the details section for the layout of the file.

verbose

If TRUE, give verbose output

Details

inputfile layout: Num Name Chr cM 1 X3.Hydroxypropyl 4 50.0 Num is the number of the phenotype in the cross object Name is the name of the phenotype (will be checked against the name already in the cross object at position num Chr Chromosome cM position from start of chromosome in cM

Value

The input cross object, with the locations added as an additional component locations

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

## Not run: 
    data(multitrait)
    data(locations)
    multiloc <- addloctocross(multitrait,locations)
    results <- scanall(multiloc)
    mqmplot.cistrans(results, multiloc, 5, FALSE, TRUE)
  
## End(Not run)

Add a marker to a cross

Description

Add a marker to a cross object.

Usage

addmarker(cross, genotypes, markername, chr, pos)

Arguments

cross

An object of class cross. See read.cross for details.

genotypes

Vector of numeric genotypes.

markername

Marker name as character string.

chr

Chromosome ID as character string.

pos

Position of marker, as numeric value.

Details

Use this function with caution. It would be best to incorporate new data into a single file to be imported with read.cross.

But if you have genotypes on one or two additional markers that you want to add, you might load them with read.csv and incorporate them with this function.

Value

The input cross object with the single marker added.

Author(s)

Karl W Broman, [email protected]

See Also

pull.markers, drop.markers

Examples

data(fake.f2)

# genotypes for new marker
gi <- pull.geno(fill.geno(fake.f2))[,"D5M197"]

# add marker to cross
fake.f2 <- addmarker(fake.f2, gi, "D5M197imp", "5", 11)

Scan for an additional pair of QTL in a multiple-QTL model

Description

Scan for an additional pair of QTL in the context of a multiple QTL model.

Usage

addpair(cross, chr, pheno.col=1, qtl, covar=NULL, formula,
        method=c("imp","hk"), model=c("normal", "binary"),
        incl.markers=FALSE, verbose=TRUE, tol=1e-4, maxit=1000,
        forceXcovar=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to be scanned. If missing, all chromosomes are scanned. Refer to chromosomes by name. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix to be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

An object of class qtl, as output from makeqtl.

covar

A matrix or data.frame of covariates. These must be strictly numeric.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are referred to as Q1, Q2, etc. Covariates are referred to by their names in the data frame covar. If the new QTL are not included in the formula, a two-dimensional scan as in scantwo is performed.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

incl.markers

If FALSE, do calculations only at points on an evenly spaced grid. If calc.genoprob or sim.geno were run with stepwidth="variable" or stepwidth="max", we force incl.markers=TRUE.

verbose

If TRUE, display information about the progress of calculations. If verbose is an integer > 1, further messages from scanqtl are also displayed.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

forceXcovar

If TRUE, force inclusion of X-chr-related covariates (like sex and cross direction).

Details

The formula is used to specified the model to be fit. In the formula, use Q1, Q2, etc., or q1, q2, etc., to represent the QTLs, and the column names in the covariate data frame to represent the covariates.

We enforce a hierarchical structure on the model formula: if a QTL or covariate is in involved in an interaction, its main effect must also be included.

If neither of the two new QTL are indicated in the formula, we perform a two-dimensional scan as in scantwo. That is, for each pair of QTL positions, we fit two models: two additive QTL added to the formula, and two interacting QTL added to the formula.

If the both of the new QTL are indicated in the formula, that particular model is fit, with the positions of the new QTL allowed to vary across the genome. If just one of the QTL is indicated in the formula, a main effect for the other is added, and that particular model is fit, again with the positions of both QTL varying. Note that in this case the LOD scores are not analogous to those produced by scantwo. Thus, there slightly modified forms for the plots (produced by plot.scantwo) and summaries (produced by summary.scantwo and max.scantwo). In the plot, the x-axis is to be interpreted as the position of the first of the new QTL, and the y-axis is to be interpreted as the position of the second of the new QTL. In the summaries, we give the single best pair of positions on each pair of chromosomes, and give LOD scores comparing that pair of positions to the base model (without each of these QTL), and to the base model plus one additional QTL on one or the other of the chromosomes.

Value

An object of class scantwo, as produced by scantwo.

If neither of the new QTL were indicated in the formula, the result is just as in scantwo, though with LOD scores relative to the base model (omitting the new QTL).

Otherwise, the results are contained in what would ordinarily be in the full and additive LOD scores, with the additive LOD scores corresponding to the case that the first of the new QTL is to the left of the second of the new QTL, and the full LOD scores corresponding to the case that the first of the new QTL is to the right of the second of the new QTL. Because the structure of the LOD scores in this case is different from those output by scantwo, we include, in this case, an attribute "addpair"=TRUE. (We also require results of single-dimensional scans, omitting each of the two new QTL from the formula, one at a time; these are included as attributes "lod.minus1" and "lod.minus2".) The results are then treated somewhat differently by summary.scantwo, max.scantwo, and plot.scantwo. See the Details section.

Author(s)

Karl W Broman, [email protected]

References

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

addint, addqtl, fitqtl, makeqtl, scanqtl, refineqtl, makeqtl, scantwo, addtoqtl

Examples

# A totally contrived example to show some of what you can do

# simulate backcross data with 3 chromosomes (names "17", "18", "19")
#   one QTL on chr 17 at 40 cM
#   one QTL on chr 18 at 30 cM
#   two QTL on chr 19, at 10 and 40 cM
data(map10)
model <- rbind(c(1,40,0), c(2,30,0), c(3,10,0), c(3,40,0))
## Not run: fakebc <- sim.cross(map10[17:19], model=model, type="bc", n.ind=250)


# het at QTL on 17 and 1st QTL on 19 increases phenotype by 1 unit
# het at QTL on 18 and 2nd QTL on 19 decreases phenotype by 1 unit
qtlgeno <- fakebc$qtlgeno
phe <- rnorm(nind(fakebc))
w <- qtlgeno[,1]==2 & qtlgeno[,3]==2
phe[w] <- phe[w] + 1
w <- qtlgeno[,2]==2 & qtlgeno[,4]==2
phe[w] <- phe[w] - 1
fakebc$pheno[,1] <- phe

## Not run: fakebc <- calc.genoprob(fakebc, step=2, err=0.001)


# base model has QTLs on chr 17 and 18
qtl <- makeqtl(fakebc, chr=c("17", "18"), pos=c(40,30), what="prob")

# scan for an additional pair of QTL, one interacting with the locus
#     on 17 and one interacting with the locus on 18
out.ap <- addpair(fakebc, qtl=qtl, formula = y~Q1*Q3 + Q2*Q4, method="hk")

max(out.ap)
summary(out.ap)
plot(out.ap)

Scan for an additional QTL in a multiple-QTL model

Description

Scan for an additional QTL in the context of a multiple QTL model.

Usage

addqtl(cross, chr, pheno.col=1, qtl, covar=NULL, formula,
       method=c("imp","hk"), model=c("normal", "binary"),
       incl.markers=TRUE, verbose=FALSE, tol=1e-4, maxit=1000,
       forceXcovar=FALSE, require.fullrank=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to be scanned. If missing, all chromosomes are scanned. Refer to chromosomes by name. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix to be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

An object of class qtl, as output from makeqtl.

covar

A matrix or data.frame of covariates. These must be strictly numeric.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are referred to as Q1, Q2, etc. Covariates are referred to by their names in the data frame covar. If the new QTL is not included in the formula, its main effect is added.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

incl.markers

If FALSE, do calculations only at points on an evenly spaced grid. If calc.genoprob or sim.geno were run with stepwidth="variable" or stepwidth="max", we force incl.markers=TRUE.

verbose

If TRUE, display information about the progress of calculations. If verbose is an integer > 1, further messages from scanqtl are also displayed.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

forceXcovar

If TRUE, force inclusion of X-chr-related covariates (like sex and cross direction).

require.fullrank

If TRUE, give LOD=0 when covariate matrix in the linear regression is not of full rank.

Details

The formula is used to specified the model to be fit. In the formula, use Q1, Q2, etc., or q1, q2, etc., to represent the QTLs, and the column names in the covariate data frame to represent the covariates.

We enforce a hierarchical structure on the model formula: if a QTL or covariate is in involved in an interaction, its main effect must also be included.

If one wishes to scan for QTL that interact with another QTL, include it in the formula (with an index of one more than the number of QTL in the input qtl object).

Value

An object of class scanone, as produced by the scanone function. LOD scores are relative to the base model (with any terms that include the new QTL omitted).

Author(s)

Karl W Broman, [email protected]

References

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

scanone, fitqtl, scanqtl, refineqtl, makeqtl, addtoqtl, addpair, addint

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 8, 13)
qp <- c(26, 56, 28)

fake.f2 <- subset(fake.f2, chr=c(1,2,3,8,13))


fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

# scan for an additional QTL
out1 <- addqtl(fake.f2, qtl=qtl, formula=y~Q1+Q2+Q3, method="hk")
max(out1)

# scan for an additional QTL that interacts with the locus on chr 1
out2 <- addqtl(fake.f2, qtl=qtl, formula=y~Q1*Q4+Q2+Q3, method="hk")
max(out2)

# plot interaction LOD scores
plot(out2-out1)

Add to a qtl object

Description

Add a QTL or multiple QTL to a qtl object.

Usage

addtoqtl(cross, qtl, chr, pos, qtl.name, drop.lod.profile=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

qtl

The qtl object to which additional QTL are to be added.

chr

Vector indicating the chromosome for each new QTL. (These should be character strings referring to the chromosomes by name.)

pos

Vector (of same length as chr) indicating the positions on the chromosome for each new QTL. If there is no marker or pseudomarker at a position, the nearest position is used.

qtl.name

Optional user-specified name for each new QTL, used in the drop-one-term ANOVA table in fitqtl. If unspecified, the names will be of the form "Chr1@10" for a QTL on Chromsome 1 at 10 cM.

drop.lod.profile

If TRUE, remove any LOD profiles from the object.

Value

An object of class qtl, just like the input qtl object, but with additional QTL added. See makeqtl for details.

Author(s)

Karl W Broman, [email protected]

See Also

makeqtl, fitqtl, dropfromqtl, replaceqtl, reorderqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 6, 13)
qp <- c(25.8, 33.6, 18.63)


fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")
qtl <- addtoqtl(fake.f2, qtl, 14, 35)

Test all possible splits of a chromosome into two pieces

Description

In order to assess the support for a linkage group, this function splits the linkage groups into two pieces at each interval and in each case calculates a LOD score comparing the combined linkage group to the two pieces.

Usage

allchrsplits(cross, chr, error.prob=0.0001,
                map.function=c("haldane","kosambi","c-f","morgan"),
                m=0, p=0, maxit=4000, tol=1e-6, sex.sp=TRUE,
                verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

A vector specifying which chromosomes to study. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions. (Ignored if m > 0.)

m

Interference parameter for the chi-square model for interference; a non-negative integer, with m=0 corresponding to no interference. This may be used only for a backcross or intercross.

p

Proportion of chiasmata from the NI mechanism, in the Stahl model; p=0 gives a pure chi-square model. This may be used only for a backcross or intercross.

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

verbose

If TRUE, print information on progress.

Value

A data frame (actually, an object of class "scanone", so that one may use plot.scanone, summary.scanone, etc.) with each row being an interval at which a split is made. The first two columns are the chromosome ID and midpoint of the interval. The third column is a LOD score comparing the combined linkage group to the split into two linkage groups. A fourth column (gap) indicates the length of each interval.

The row names indicate the flanking markers for each interval.

Author(s)

Karl W Broman, [email protected]

See Also

est.map, ripple, est.rf, switch.order, movemarker

Examples

data(fake.bc)
allchrsplits(fake.bc, 7, error.prob=0, verbose=FALSE)

Reconstruct underlying genotypes

Description

Uses the Viterbi algorithm to identify the most likely sequence of underlying genotypes, given the observed multipoint marker data, with possible allowance for genotyping errors.

Usage

argmax.geno(cross, step=0, off.end=0, error.prob=0.0001,
            map.function=c("haldane","kosambi","c-f","morgan"),
            stepwidth=c("fixed", "variable", "max"))

Arguments

cross

An object of class cross. See read.cross for details.

step

Maximum distance (in cM) between positions at which the genotypes are reconstructed, though for step=0, genotypes are reconstructed only at the marker locations.

off.end

Distance (in cM) past the terminal markers on each chromosome to which the genotype reconstructions will be carried.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer or Morgan map function when converting genetic distances into recombination fractions.

stepwidth

Indicates whether the intermediate points should with fixed or variable step sizes. We recommend using "fixed"; "variable" was included for the qtlbim package (https://cran.r-project.org/src/contrib/Archive/qtlbim/). The "max" option inserts the minimal number of intermediate points so that the maximum distance between points is step.

Details

We use the Viterbi algorithm to calculate argmaxvPr(g=vO)\arg \max_v \Pr(g = v | O) where gg is the underlying sequence of genotypes and OO is the observed marker genotypes.

This is done by calculating γk(vk)=maxv1,,vk1Pr(g1=v1,,gk=vk,O1,,Ok)\gamma_k(v_k) = \max_{v_1, \ldots, v_{k-1}} \Pr(g_1 = v_1, \ldots, g_k = v_k, O_1, \ldots, O_k) for k=1,,nk = 1, \ldots, n and then tracing back through the sequence.

Value

The input cross object is returned with a component, argmax, added to each component of cross$geno. The argmax component is a matrix of size [n.ind x n.pos], where n.pos is the number of positions at which the reconstructed genotypes were obtained, containing the most likely sequences of underlying genotypes. Attributes "error.prob", "step", and "off.end" are set to the values of the corresponding arguments, for later reference.

Warning

The Viterbi algorithm can behave badly when step is small but positive. One may observe quite different results for different values of step.

The problem is that, in the presence of data like A----H, the sequences AAAAAA and HHHHHH may be more likely than any one of the sequences AAAAAH, AAAAHH, AAAHHH, AAHHHH, AHHHHH, AAAAAH. The Viterbi algorithm produces a single "most likely" sequence of underlying genotypes.

Author(s)

Karl W Broman, [email protected]

References

Lange, K. (1999) Numerical analysis for statisticians. Springer-Verlag. Sec 23.3.

Rabiner, L. R. (1989) A tutorial on hidden Markov models and selected applications in speech recognition. Proceedings of the IEEE 77, 257–286.

See Also

sim.geno, calc.genoprob, fill.geno

Examples

data(fake.f2)
fake.f2 <- argmax.geno(fake.f2, step=2, off.end=5, err=0.01)

Arithmetic operators for scanone and scantwo results

Description

Add or subtract LOD scores in results from scanone or scantwo.

Usage

scan1+scan2
scan1-scan2

Arguments

scan1, scan2

Genome scan results on the same set of chromosomes and markers, as output by scanone or scantwo.

Details

This is used to calculate the sum or difference of LOD scores of two genome scan results. It is particularly useful for calculating the LOD scores for QTL-by-covariate interactions (see the example, below). Note that the degrees of freedom are also added or subtracted.

Value

The same type of data structure as the input objects, with LOD scores added or subtracted.

Author(s)

Karl W Broman, [email protected]

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=2.5)

# covariates
ac <- pull.pheno(fake.bc, c("sex","age"))
ic <- pull.pheno(fake.bc, "sex")

# scan with additive but not the interactive covariate
out.acovar <- scanone(fake.bc, addcovar=ac)

# scan with interactive covariate
out.icovar <- scanone(fake.bc, addcovar=ac, intcovar=ic)

# plot the difference of with and without the interactive covariate
#     This is a LOD score for a test of QTL x covariate interaction
plot(out.icovar-out.acovar)

Arithmetic Operators for permutation results

Description

Add or subtract LOD scores in permutation results from scanone or scantwo.

Usage

perm1+perm2
perm1-perm2

Arguments

perm1, perm2

Permutation results from scanone or scantwo, on the same set of chromosomes and markers.

Details

This is used to calculate the sum or difference of LOD scores of two sets of permutation results from scanone or scantwo. One must be careful to ensure that the permutations are perfectly linked, which will require the use of set.seed.

Value

The same data structure as the input objects, with LOD scores added or subtracted.

Author(s)

Karl W Broman, [email protected]

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=2.5)

# covariates
ac <- pull.pheno(fake.bc, c("sex","age"))
ic <- pull.pheno(fake.bc, "sex")

# set seed
theseed <- round(runif(1, 1, 10^8))
set.seed(theseed)

# permutations with additive but not the interactive covariate
## Not run: operm.acovar <- scanone(fake.bc, addcovar=ac, n.perm=1000)


# re-set the seed
set.seed(theseed)

# permutations with interactive covariate
## Not run: operm.icovar <- scanone(fake.bc, addcovar=ac, intcovar=ic,
                      n.perm=1000)

## End(Not run)

# permutation results for the QTL x covariate interaction
operm.gxc <- operm.icovar - operm.acovar

# LOD thresholds
summary(operm.gxc)

An intercross with misplaced markers

Description

Simulated data for an intercross with some markers out of order.

Usage

data(badorder)

Format

An object of class cross. See read.cross for details.

Details

There are 250 F2 individuals typed at a total of 36 markers on four chromosomes. The data were simulated with QTLs at the center of chromosomes 1 and 3.

The order of several markers on chromosome 1 is incorrect. Markers on chromosomes 2 and 3 are switched.

Author(s)

Karl W Broman, [email protected]

See Also

est.rf, ripple, est.map, sim.cross

Examples

data(badorder)

# estimate recombination fractions
badorder <- est.rf(badorder)
plotRF(badorder)

# re-estimate map
newmap <- est.map(badorder)
plotMap(badorder, newmap)

# assess marker order on chr 1
rip3 <- ripple(badorder, chr=1, window=3)
summary(rip3)

Bayesian credible interval

Description

Calculate an approximate Bayesian credible interval for a particular chromosome, using output from scanone.

Usage

bayesint(results, chr, qtl.index, prob=0.95, lodcolumn=1, expandtomarkers=FALSE)

Arguments

results

Output from scanone, or a qtl object as output from refineqtl.

chr

A chromosome ID (if input results are from scanone (should have length 1).

qtl.index

Numeric index for a QTL (if input results are from refineqtl (should have length 1).

prob

Probability coverage of the interval.

lodcolumn

An integer indicating which of the LOD score columns should be considered (if input results are from scanone).

expandtomarkers

If TRUE, the interval is expanded to the nearest flanking markers.

Details

We take 10LOD10^{LOD}, rescale it to have area 1, and then calculate the connected interval with density above some threshold and having coverage matching the target probability.

Value

An object of class scanone indicating the estimated QTL position and the approximate endpoints for the Bayesian credible interval.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, lodint

Examples

data(hyper)

hyper <- calc.genoprob(hyper, step=0.5)
out <- scanone(hyper, method="hk")
bayesint(out, chr=1)
bayesint(out, chr=4)
bayesint(out, chr=4, prob=0.99)
bayesint(out, chr=4, expandtomarkers=TRUE)

Data on bristle number in Drosophila

Description

Data from bristle number in chromosome 3 recombinant isogenic lines of Drosophila melanogaster.

Usage

data(bristle3)

Format

An object of class cross. See read.cross for details.

Details

There are 66 chromosome 3 recombinant isogenic lines, derived from inbred lines that were selected for low (A) and high (B) abdominal bristle numbers. A recombinant chromosome 3 was placed in an isogenic low background.

There are eight phenotypes: the average and SD of the number of abdominal and sternopleural bristles in males and females for each line.

Each line is typed at 29 genetic markers on chromosome 3.

References

Long, A. D., Mullaney, S. L., Reid, L. A., Fry, J. D., Langley, C. H. and MacKay, T. F. C. (1995) High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster. Genetics 139, 1273–1291.

See Also

bristleX, listeria, fake.bc, fake.f2, fake.4way, hyper

Examples

data(bristle3)
# Summaries
summary(bristle3)
plot(bristle3)

# genome scan for each of the average phenotypes
bristle3 <- calc.genoprob(bristle3, step=2)
out <- scanone(bristle3, pheno.col=c(1,3,5,7))

# Plot the results
    # maximum LOD score among four phenotypes
ym <- max(apply(out[,-(1:2)], 2, max))
plot(out, lod=1:3, ylim=c(0,ym))
plot(out, lod=4, add=TRUE, col="green")

Data on bristle number in Drosophila

Description

Data from bristle number in chromosome X recombinant isogenic lines of Drosophila melanogaster.

Usage

data(bristleX)

Format

An object of class cross. See read.cross for details.

Details

There are 92 chromosome X recombinant isogenic lines, derived from inbred lines that were selected for low (A) and high (B) abdominal bristle numbers. A recombinant chromosome X was placed in an isogenic low background.

There are eight phenotypes: the average and SD of the number of abdominal and sternopleural bristles in males and females for each line.

Each line is typed at 17 genetic markers on chromosome 3.

References

Long, A. D., Mullaney, S. L., Reid, L. A., Fry, J. D., Langley, C. H. and MacKay, T. F. C. (1995) High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster. Genetics 139, 1273–1291.

See Also

bristleX, listeria, fake.bc, fake.f2, fake.4way, hyper

Examples

data(bristleX)
# Summaries
summary(bristleX)
plot(bristleX)

# genome scan for each of the average phenotypes
bristleX <- calc.genoprob(bristleX, step=2)
out <- scanone(bristleX, pheno.col=c(1,3,5,7))

# Plot the results
    # maximum LOD score among four phenotypes
ym <- max(apply(out[,-(1:2)], 2, max))
plot(out, lod=1:3, ylim=c(0,ym))
plot(out, lod=4, add=TRUE, col="green")

Combine data for QTL experiments

Description

Concatenate the data for multiple QTL experiments.

Usage

## S3 method for class 'cross'
c(...)

Arguments

...

A set of objects of class cross. See read.cross for details. These must all either be of the same cross type or be a combination of backcrosses and intercrosses. All crosses must have the same number of chromosomes and chromosome names, and the same marker orders and positions, though the set of markers need not be precisely the same.

Value

The concatenated input, as a cross object. Additional columns are added to the phenotype data indicating which cross an individual comes from; another column indicates cross type (0=BC, 1=intercross), if there are crosses of different types. The crosses are not required to have exactly the same set of phenotypes; phenotypes with the same names are assumed to be the same.

If the crosses have different sets of markers, we interpolate marker order, but the cM positions of markers that are in common between crosses must be precisely the same in the different crosses.

Author(s)

Karl W Broman, [email protected]

See Also

subset.cross

Examples

data(fake.f2)
junk <- fake.f2
junk <- c(fake.f2,junk)

Combine columns from multiple scanone results

Description

Concatenate the columns from different runs of scanone.

Usage

## S3 method for class 'scanone'
c(..., labels)
## S3 method for class 'scanone'
cbind(..., labels)

Arguments

...

A set of objects of class scanone. (This can also be a list of scanone objects.) These are the results from scanone (with n.perm=0), generally run with different phenotypes or methods. All must conform with each other, meaning that calc.genoprob and/or sim.geno were run with the same values for step and off.end and with data having the same genetic map.

labels

A vector of character strings, of length 1 or of the same length as the input, to be appended to the column names in the output.

Details

The aim of this function is to concatenate the results from multiple runs scanone, generally for different phenotypes and/or methods, to be used in parallel with summary.scanone.

Value

The concatenated input, as a scanone object.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scanone, scanone, cbind.scanoneperm

Examples

data(fake.f2)
fake.f2 <- calc.genoprob(fake.f2)

out.hk <- scanone(fake.f2, method="hk")
out.np <- scanone(fake.f2, model="np")

out <- c(out.hk, out.np, labels=c("hk","np"))
plot(out, lod=1:2, col=c("blue", "red"))

Combine data from scanone permutations

Description

Concatenate the data for multiple runs of scanone with n.perm > 0.

Usage

## S3 method for class 'scanoneperm'
c(...)
## S3 method for class 'scanoneperm'
rbind(...)

Arguments

...

A set of objects of class scanoneperm. (This can also be a list of scanoneperm objects.) These are the permutation results from scanone (that is, when n.perm > 0). These must all have the same number of columns. (That is, they must have been created with the same number of phenotypes, and it is assumed that they were generated in precisely the same way.)

Details

The aim of this function is to concatenate the results from multiple runs of a permutation test scanone, to assist with the case that such permutations are done on multiple processors in parallel.

Value

The concatenated input, as a scanoneperm object.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scanoneperm, scanone, cbind.scanoneperm, c.scantwoperm

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2)
operm1 <- scanone(fake.f2, method="hk", n.perm=100, perm.Xsp=TRUE)
operm2 <- scanone(fake.f2, method="hk", n.perm=50, perm.Xsp=TRUE)

operm <- c(operm1, operm2)

Combine columns from multiple scantwo results

Description

Concatenate the columns from different runs of scantwo.

Usage

## S3 method for class 'scantwo'
c(...)
## S3 method for class 'scantwo'
cbind(...)

Arguments

...

A set of objects of class scantwo. (This can also be a list of scantwo objects.) These are the results from scantwo (with n.perm=0), generally run with different phenotypes or methods. All must conform with each other, meaning that calc.genoprob and/or sim.geno were run with the same values for step and off.end and with data having the same genetic map.

Details

The aim of this function is to concatenate the results from multiple runs scantwo, generally for different phenotypes and/or methods.

Value

The concatenated input, as a scantwo object.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scantwo, scantwo, c.scanone

Examples

data(fake.bc)
fake.bc <- calc.genoprob(fake.bc)

out2a <- scantwo(fake.bc, method="hk")
out2b <- scantwo(fake.bc, pheno.col=2, method="hk")

out2 <- c(out2a, out2b)

Combine data from scantwo permutations

Description

Concatenate the data for multiple runs of scantwo with n.perm > 0.

Usage

## S3 method for class 'scantwoperm'
c(...)
## S3 method for class 'scantwoperm'
rbind(...)

Arguments

...

A set of objects of class scantwoperm. (This can also be a list of scantwoperm objects.) These are the permutation results from scantwo (that is, when n.perm > 0). These must all concern the same number of LOD columns. (That is, they must have been created with the same number of phenotypes, and it is assumed that they were generated in precisely the same way.)

Details

The aim of this function is to concatenate the results from multiple runs of a permutation test scantwo, to assist with the case that such permutations are done on multiple processors in parallel.

Value

The concatenated input, as a scantwoperm object.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scantwoperm, scantwo, cbind.scantwoperm

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2)
## Not run: operm1 <- scantwo(fake.f2, method="hk", n.perm=50)
operm2 <- scantwo(fake.f2, method="hk", n.perm=50)
## End(Not run)

operm <- c(operm1, operm2)

Identify likely genotyping errors

Description

Calculates a LOD score for each genotype, measuring the evidence for genotyping errors.

Usage

calc.errorlod(cross, error.prob=0.01,
              map.function=c("haldane","kosambi","c-f","morgan"),
              version=c("new","old"))

Arguments

cross

An object of class cross. See read.cross for details.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype)

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions.

version

Specifies whether to use the original version of this function or the current (preferred) version.

Details

Calculates, for each individual at each marker, a LOD score measuring the strength of evidence for a genotyping error, as described by Lincoln and Lander (1992).

In the latest version, evidence for a genotype being in error is considered assuming that all other genotypes (for that individual, on that chromosome) are correct. The argument version allows one to specify whether this new version is used, or whether the original (old) version of the calculation is performed.

Note that values below 4 are generally not interesting. Also note that if markers are extremely tightly linked, recombination events can give large error LOD scores. The error LOD scores should not be trusted blindly, but should be viewed as a tool for identifying genotypes deserving further study.

Use top.errorlod to print all genotypes with error LOD scores above a specified threshold, plotErrorlod to plot the error LOD scores for specified chromosomes, and plotGeno to view the observed genotype data with likely errors flagged.

Value

The input cross object is returned with a component, errorlod, added to each component of cross$geno. The errorlod component is a matrix of size (n.ind x n.mar). An attribute "error.prob" is set to the value of the corresponding argument, for later reference.

Author(s)

Karl W Broman, [email protected]

References

Lincoln, S. E. and Lander, E. S. (1992) Systematic detection of errors in genetic linkage data. Genomics 14, 604–610.

See Also

plotErrorlod, top.errorlod, cleanGeno

Examples

data(hyper)

hyper <- calc.errorlod(hyper,error.prob=0.01)

# print those above a specified cutoff
top.errorlod(hyper, cutoff=4)

# plot genotype data, flagging genotypes with error LOD > cutoff
plotGeno(hyper, chr=1, ind=160:200, cutoff=7, min.sep=2)

Calculate conditional genotype probabilities

Description

Uses the hidden Markov model technology to calculate the probabilities of the true underlying genotypes given the observed multipoint marker data, with possible allowance for genotyping errors.

Usage

calc.genoprob(cross, step=0, off.end=0, error.prob=0.0001,
              map.function=c("haldane","kosambi","c-f","morgan"),
              stepwidth=c("fixed", "variable", "max"))

Arguments

cross

An object of class cross. See read.cross for details.

step

Maximum distance (in cM) between positions at which the genotype probabilities are calculated, though for step = 0, probabilities are calculated only at the marker locations.

off.end

Distance (in cM) past the terminal markers on each chromosome to which the genotype probability calculations will be carried.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi or Carter-Falconer map function when converting genetic distances into recombination fractions.

stepwidth

Indicates whether the intermediate points should with fixed or variable step sizes. We recommend using "fixed"; "variable" was included for the qtlbim package (https://cran.r-project.org/src/contrib/Archive/qtlbim/). The "max" option inserts the minimal number of intermediate points so that the maximum distance between points is step.

Details

Let OkO_k denote the observed marker genotype at position kk, and gkg_k denote the corresponding true underlying genotype.

We use the forward-backward equations to calculate αkv=logPr(O1,,Ok,gk=v)\alpha_{kv} = \log Pr(O_1, \ldots, O_k, g_k = v) and βkv=logPr(Ok+1,,Ongk=v)\beta_{kv} = \log Pr(O_{k+1}, \ldots, O_n | g_k = v)

We then obtain Pr(gkO1,,On)=exp(αkv+βkv)/sPr(g_k | O_1, \ldots, O_n) = \exp(\alpha_{kv} + \beta_{kv}) / s where s=vexp(αkv+βkv)s = \sum_v \exp(\alpha_{kv} + \beta_{kv})

In the case of the 4-way cross, with a sex-specific map, we assume a constant ratio of female:male recombination rates within the inter-marker intervals.

Value

The input cross object is returned with a component, prob, added to each component of cross$geno. prob is an array of size [n.ind x n.pos x n.gen] where n.pos is the number of positions at which the probabilities were calculated and n.gen = 3 for an intercross, = 2 for a backcross, and = 4 for a 4-way cross. Attributes "error.prob", "step", "off.end", and "map.function" are set to the values of the corresponding arguments, for later reference (especially by the function calc.errorlod).

Author(s)

Karl W Broman, [email protected]

References

Lange, K. (1999) Numerical analysis for statisticians. Springer-Verlag. Sec 23.3.

Rabiner, L. R. (1989) A tutorial on hidden Markov models and selected applications in speech recognition. Proceedings of the IEEE 77, 257–286.

See Also

sim.geno, argmax.geno, calc.errorlod

Examples

data(fake.f2)
fake.f2 <- calc.genoprob(fake.f2, step=2, off.end=5)

data(fake.bc)
fake.bc <- calc.genoprob(fake.bc, step=0, off.end=0, err=0.01)

Calculate LOD penalties

Description

Derive penalties for the penalized LOD scores (used by stepwiseqtl) on the basis of permutation results from a two-dimensional, two-QTL scan (obtained by scantwo).

Usage

calc.penalties(perms, alpha=0.05, lodcolumn)

Arguments

perms

Permutation results from scantwo.

alpha

Significance level.

lodcolumn

If the scantwo permutation results contain LOD scores for multiple phenotypes, this argument indicates which to use in the summary. This may be a vector. If missing, penalties for all phenotypes are calculated.

Details

Thresholds derived from scantwo permutations (that is, for a two-dimensional, two-QTL genome scan) are used to calculate penalties on main effects and interactions.

The main effect penalty is the 1-alpha quantile of the null distribution of the genome-wide maximum LOD score from a single-QTL genome scan (as with scanone).

The "heavy" interaction penalty is the 1-alpha quantile of the null distribution of the maximum interaction LOD score (that is, the log10\log_{10} likelihood ratio comparing the best model with two interacting QTL to the best model with two additive QTL) from a two-dimensional, two-QTL genome scan (as with scantwo).

The "light" interaction penality is the difference between the "fv1" threshold from the scantwo permutations (that is, the 1-alpha quantile of the LOD score comparing the best model with two interacting QTL to the best single-QTL model) and the main effect penalty.

If the permutations results were obtained with perm.Xsp=TRUE, to give X-chr-specific results, six penalties are calculated: main effect for autosomes, main effect for X chr, heavy penalty on A:A interactions, light penalty on A:A interactions, penalty on A:X interactions, and penalty on X:X interactions.

Value

Vector of three values indicating the penalty on main effects and heavy and light penalties on interactions, or a matrix of such results, with each row corresponding to a different phenotype.

If the input permutations are X-chromosome-specific, the result has six values: main effect for autosomes, main effect for X chr, heavy penalty on A:A interactions, light penalty on A:A interactions, penalty on A:X interactions, and penalty on X:X interactions.

Author(s)

Karl W Broman, [email protected]

References

Manichaikul, A., Moon, J. Y., Sen, Ś, Yandell, B. S. and Broman, K. W. (2009) A model selection approach for the identification of quantitative trait loci in experimental crosses, allowing epistasis. Genetics, 181, 1077–1086.

See Also

scantwo, stepwiseqtl

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=5)
out.2dim <- scantwo(fake.f2, method="hk")

# permutations

## Not run: permo.2dim <- scantwo(fake.f2, method="hk", n.perm=1000)
summary(permo.2dim, alpha=0.05)

# penalties
calc.penalties(permo.2dim)

Combine columns from multiple scanone permutation results

Description

Concatenate the columns from different runs of scanone with n.perm > 0.

Usage

## S3 method for class 'scanoneperm'
cbind(..., labels)

Arguments

...

A set of objects of class scanoneperm. These are the permutation results from scanone (that is, when n.perm > 0), generally run with different phenotypes or methods.

labels

A vector of character strings, of length 1 or of the same length as the input ..., to be appended to the column names in the output.

Details

The aim of this function is to concatenate the results from multiple runs of a permutation test scanone, generally for different phenotypes and/or methods, to be used in parallel with c.scanone.

Value

The concatenated input, as a scanoneperm object. If different numbers of permutation replicates were used, those columns with fewer replicates are padded with missing values (NA).

Author(s)

Karl W Broman, [email protected]

See Also

summary.scanoneperm, scanone, c.scanoneperm, c.scanone

Examples

data(fake.f2)
fake.f2 <- calc.genoprob(fake.f2)

operm1 <- scanone(fake.f2, method="hk", n.perm=10, perm.Xsp=TRUE)
operm2 <- scanone(fake.f2, method="em", n.perm=5, perm.Xsp=TRUE)

operm <- cbind(operm1, operm2, labels=c("hk","em"))
summary(operm)

Combine scantwo permutations by column

Description

Column-bind permutations results from scantwo for multiple phenotypes or models.

Usage

## S3 method for class 'scantwoperm'
cbind(...)

Arguments

...

A set of objects of class scantwoperm. (This can also be a list of scantwoperm objects.) These are the permutation results from scantwo (that is, when n.perm > 0). These must all concern the same number of permutations.

Value

The column-binded input, as a scantwoperm object.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, c.scantwoperm, summary.scantwoperm

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc)
## Not run: operm1 <- scantwo(fake.bc, pheno.col=1, method="hk", n.perm=50)
operm2 <- scantwo(fake.bc, pheno.col=2, method="hk", n.perm=50)
## End(Not run)

operm <- cbind(operm1, operm2)

Identify markers with switched alleles

Description

Identify markers whose alleles might have been switched by comparing the LOD score for linkage to all other autosomal markers with the original data to that when the alleles have been switched.

Usage

checkAlleles(cross, threshold=3, verbose)

Arguments

cross

An object of class cross. See read.cross for details.

threshold

Only an increase in maximum 2-point LOD of at least this amount will lead to a marker being flagged.

verbose

If TRUE and there are no markers above the threshold, print a message.

Details

For each marker, we compare the maximum LOD score for the cases where the estimated recombination fraction > 0.5 to those where r.f. < 0.5. The function est.rf must first be run.

Note: Markers that are tightly linked to a marker whose alleles are switched are likely to also be flagged by this method. The real problem markers are likely those with the biggest difference in LOD scores.

Value

A data frame containing the flagged markers, having four columns: the marker name, chromosome ID, numeric index within chromosome, and the difference between the maximum two-point LOD score with the alleles switched to that from the original data.

Author(s)

Karl W Broman, [email protected]

See Also

est.rf, geno.crosstab, switchAlleles

Examples

data(fake.f2)


# switch homozygotes at marker D5M391
fake.f2 <- switchAlleles(fake.f2, "D5M391")

fake.f2 <- est.rf(fake.f2)
checkAlleles(fake.f2)

Chromosome lengths in QTL experiment

Description

Obtain the chromosome lengths in a cross or map object.

Usage

chrlen(object)

Arguments

object

An object of class map or of class cross.

Value

Returns a vector of chromosome lengths. If the cross has sex-specific maps, it returns a 2-row matrix with the two lengths for each chromosome.

Author(s)

Karl W Broman, [email protected]

See Also

summaryMap, pull.map, summary.cross

Examples

data(fake.f2)
chrlen(fake.f2)

map <- pull.map(fake.f2)
chrlen(map)

Pull out the chromosome names from a cross

Description

Pull out the chromosome names from a cross object as one big vector.

Usage

chrnames(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Value

A vector of character strings (the chromosome names).

Author(s)

Karl W Broman, [email protected]

See Also

markernames, phenames

Examples

data(listeria)
chrnames(listeria)

Composite interval mapping

Description

Composite interval mapping by a scheme from QTL Cartographer: forward selection at the markers (here, with filled-in genotype data) to a fixed number, followed by interval mapping with the selected markers as covariates, dropping marker covariates if they are within some fixed window size of the location under test.

Usage

cim(cross, pheno.col=1, n.marcovar=3, window=10,
    method=c("em", "imp", "hk", "ehk"),
    imp.method=c("imp", "argmax"), error.prob=0.0001,
    map.function=c("haldane", "kosambi", "c-v", "morgan"),
    addcovar=NULL, n.perm)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

n.marcovar

Number of marker covariates to use.

window

Window size, in cM.

method

Indicates whether to use the EM algorithm, imputation, Haley-Knott regression, or the extended Haley-Knott method.

imp.method

Method used to impute any missing marker genotype data.

error.prob

Genotyping error probability assumed when imputing the missing marker genotype data.

map.function

Map function used when imputing the missing marker genotype data.

addcovar

Optional numeric matrix of additional covariates to include.

n.perm

If specified, a permutation test is performed rather than an analysis of the observed data. This argument defines the number of permutation replicates.

Details

We first use fill.geno to impute any missing marker genotype data, either via a simple random imputation or using the Viterbi algorithm.

We then perform forward selection to a fixed number of markers. These will be used (again, with any missing data filled in) as covariates in the subsequent genome scan.

Value

The function returns an object of the same form as the function scanone:

If n.perm is missing, the function returns the scan results as a data.frame with three columns: chromosome, position, LOD score. Attributes indicate the names and positions of the chosen marker covariates.

If n.perm > 0, the function results the results of a permutation test: a vector giving the genome-wide maximum LOD score in each of the permutations.

Author(s)

Karl W Broman, [email protected]

References

Jansen, R. C. (1993) Interval mapping of multiple quantitative trait loci. Genetics, 135, 205–211.

Jansen, R. C. and Stam, P. (1994) High resolution of quantitative traits into multiple loci via interval mapping. Genetics, 136, 1447-1455.

Zeng, Z. B. (1993) Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc. Natl. Acad. Sci. USA, 90, 10972–10976.

Zeng, Z. B. (1994) Precision mapping of quantitative trait loci. Genetics, 136, 1457–1468.

See Also

add.cim.covar, scanone, summary.scanone, plot.scanone, fill.geno

Examples

data(hyper)
hyper <- calc.genoprob(hyper, step=2.5)


out <- scanone(hyper)
out.cim <- cim(hyper, n.marcovar=3)
plot(out, out.cim, chr=c(1,4,6,15), col=c("blue", "red"))

add.cim.covar(out.cim, chr=c(1,4,6,15))

Remove derived data

Description

Remove any intermediate calculations from a cross object.

Usage

## S3 method for class 'cross'
clean(object, ...)

Arguments

object

An object of class cross. See read.cross for details.

...

Ignored at this point.

Value

The input object, with any intermediate calculations (such as is produced by calc.genoprob, argmax.geno and sim.geno) removed.

Author(s)

Karl W Broman, [email protected]

See Also

drop.nullmarkers, drop.markers, clean.scantwo

Examples

data(fake.f2)
names(fake.f2$geno)
fake.f2 <- calc.genoprob(fake.f2)
names(fake.f2$geno)
fake.f2 <- clean(fake.f2)
names(fake.f2$geno)

Clean up scantwo output

Description

In an object output from scantwo, replaces negative and missing LOD scores with 0, and replaces LOD scores for pairs of positions that are not separated by n.mar markers, or that are less than distance cM apart, with 0. Further, if the LOD for full model is less than the LOD for the additive model, the additive LOD is pasted over the full LOD.

Usage

## S3 method for class 'scantwo'
clean(object, n.mar=1, distance=0, ...)

Arguments

object

An object of class scantwo. See scantwo for details.

n.mar

Pairs of positions not separated by at least this many markers have LOD scores set to 0.

distance

Pairs of positions not separated by at least this distance have LOD scores set to 0.

...

Ignored at this point.

Value

The input scantwo object, with any negative or missing LOD scores replaced by 0, and LOD scores for pairs of positions separated by fewer than n.mar markers, or less than distance cM, are set to 0. Also, if the LOD for the full model is less than the LOD for the additive model, the additive LOD is used in place of the full LOD.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, summary.scantwo

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=5)
out2 <- scantwo(fake.f2, method="hk")
out2 <- clean(out2)
out2cl2 <- clean(out2, n.mar=2, distance=5)

Delete genotypes that are possibly in error

Description

Delete genotypes from a cross that are indicated to be possibly in error, as they result in apparent tight double-crossovers.

Usage

cleanGeno(cross, chr, maxdist=2.5, maxmark=2, verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

maxdist

A vector specifying the maximum distance between two crossovers.

maxmark

A vector specifying the maximum number of typed markers between two crossovers.

verbose

If TRUE, print information on the numbers of genotypes omitted from each chromosome.

Details

We first use locateXO to identify crossover locations. If a pair of adjacted crossovers are separated by no more than maxdist and contain no more than maxmark genotyped markers, the intervening genotypes are omitted (that is, changed to NA).

The arguments maxdist and maxmark may be vectors. (If both have length greater than 1, they must have the same length.) If they are vectors, genotypes are omitted if they satisify any one of the (maxdist, maxmark) pairs.

Value

The input cross object with suspect genotypes omitted.

Author(s)

Karl W Broman, [email protected]

See Also

locateXO, countXO, calc.errorlod

Examples

data(hyper)
sum(ntyped(hyper))
hyperc <- cleanGeno(hyper, chr=4, maxdist=c(2.5, 10), maxmark=c(2, 1))
sum(ntyped(hyperc))

Compare two cross objects

Description

Verify that two objects of class cross have identical classes, chromosomes, markers, genotypes, genetic maps, and phenotypes.

Usage

comparecrosses(cross1, cross2, tol=1e-5)

Arguments

cross1

An object of class cross (must be an intercross). See read.cross for details.

cross2

An object of class cross (must be an intercross). See read.cross for details.

tol

Tolerance value for comparing genetic map positions and numeric phenotypes.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

summary.cross

Examples

data(listeria)
comparecrosses(listeria, listeria)

Compare individuals' genotype data

Description

Count proportion of matching genotypes between all pairs of individuals, to look for unusually closely related individuals.

Usage

comparegeno(cross, what=c("proportion","number","both"))

Arguments

cross

An object of class cross. See read.cross for details.

what

Indicates whether to return the proportion or number of matching genotypes (or both).

Value

A matrix whose (i,j)th element is the proportion or number of matching genotypes for individuals i and j.

If called with what="both", the lower triangle contains the proportion and the upper triangle contains the number.

If called with what="proportion", the diagonal contains missing values. Otherwise, the diagonal contains the number of typed markers for each individual.

The output is given class "comparegeno" so that appropriate summary and plot functions may be used.

Author(s)

Karl W Broman, [email protected]

See Also

nmissing, summary.comparegeno, plot.comparegeno

Examples

data(listeria)

cg <- comparegeno(listeria)

summary(cg, 0.7)
plot(cg)

Compare two orderings of markers on a chromosome

Description

Compare the likelihood of an alternative order for markers on a chromosome to the current order.

Usage

compareorder(cross, chr, order, error.prob=0.0001,
             map.function=c("haldane","kosambi","c-f","morgan"),
             maxit=4000, tol=1e-6, sex.sp=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

The chromosome to investigate. Only one chromosome is allowed. (This should be a character string referring to the chromosomes by name.)

order

The alternate order of markers on the chromosome: a numeric vector that is a permutation of the integers from 1 to the number of markers on the chromosome.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions.

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

Value

A data frame with two rows: the current order in the input cross object, and the revised order. The first column is the log10 likelihood of the new order relative to the original one (positive values indicate that the new order is better supported). The second column is the estimated genetic length of the chromosome for each order. In the case of sex-specific maps, there are separate columns for the female and male genetic lengths.

Author(s)

Karl W Broman, [email protected]

See Also

ripple, switch.order, movemarker

Examples

data(badorder)
compareorder(badorder, chr=1, order=c(1:8,11,10,9,12))

Condense the output from a 2-d genome scan

Description

Produces a very condensed version of the output of scantwo.

Usage

## S3 method for class 'scantwo'
condense(object)

Arguments

object

An object of class scantwo, the output of the function scantwo.

Details

This produces a very reduced version of the output of scantwo, for which a summary may still be created via summary.scantwo, though plots can no longer be made.

Value

An object of class scantwocondensed, containing just the maximum full, additive and interactive LOD scores, and the positions where they occured, on each pair of chromosomes.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, summary.scantwo, max.scantwo

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2)

out2 <- scantwo(fake.f2, method="hk")

out2c <- condense(out2)
summary(out2c, allpairs=FALSE)
max(out2c)

Change map function for a genetic map

Description

Convert a genetic map from using one map function to another.

Usage

## S3 method for class 'map'
convert(object, old.map.function=c("haldane", "kosambi", "c-f", "morgan"),
         new.map.function=c("haldane", "kosambi", "c-f", "morgan"), ...)

Arguments

object

A genetic map object, of class "map": A list whose components are vectors of marker locations.

old.map.function

The map function used in forming the map in object.

new.map.function

The new map function to be used.

...

Ignored at this point.

Details

The location of the first marker on each chromosome is left unchanged. Inter-marker distances are converted to recombination fractions with the inverse of the old.map.function, and then back to distances with the new.map.function.

Value

The same as the input, but with inter-marker distances changed to reflect a different map function.

Author(s)

Karl W Broman, [email protected]

See Also

est.map, replace.map

Examples

data(listeria)
map <- pull.map(listeria)
map <- convert(map, "haldane", "kosambi")
listeria <- replace.map(listeria, map)

Convert output from scanone for R/qtl version 0.98

Description

Convert the output from scanone from the format used in R/qtl version 0.97 and earlier to that used in version 0.98 and later.

Usage

## S3 method for class 'scanone'
convert(object, ...)

Arguments

object

Output from the function scanone, for R/qtl version 0.97 and earlier.

...

Ignored at this point.

Details

Previously, inter-marker locations were named as, for example, loc7.5.c3; these were changed to c3.loc7.5.

Value

The same scanone output, but revised for use with R/qtl version 0.98 and later.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, convert.scantwo

Examples

## Not run: out.new <- convert(out.old)

Convert output from scantwo for R/qtl version 1.03 and earlier

Description

Convert the output from scantwo from the format used in R/qtl version 1.03 and earlier to that used in version 1.04 and later.

Usage

## S3 method for class 'scantwo'
convert(object, ...)

Arguments

object

Output from the function scantwo, for R/qtl version 1.03 and earlier.

...

Ignored at this point.

Details

Previously, the output from scantwo contained the full and interaction LOD scores. In R/qtl version 1.04 and later, the output contains the LOD scores from the full and additive QTL models.

Value

The same scanone output, but revised for use with R/qtl version 1.03 and later.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, convert.scanone

Examples

## Not run: out2.new <- convert(out2.old)

Convert a cross to RIL by selfing

Description

Convert a cross to type "riself" (RIL by selfing).

Usage

convert2riself(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Details

If there are more genotypes with code 3 (BB) than code 2 (AB), we omit the genotypes with code==2 and call those with code==3 the BB genotypes.

If, instead, there are more genotypes with code 2 than code 3, we omit the genotypes with code==3 and call those with code==2 the BB genotypes.

Any chromosomes with class "X" (X chromosome) are changed to class "A" (autosomal).

Value

The input cross object, with genotype codes possibly changed and cross type changed to "riself".

Author(s)

Karl W Broman, [email protected]

See Also

convert2risib

Examples

data(hyper)
hyper.as.riself <- convert2riself(hyper)

Convert a cross to RIL by sib mating

Description

Convert a cross to type "risib" (RIL by sib mating).

Usage

convert2risib(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Details

If there are more genotypes with code 3 (BB) than code 2 (AB), we omit the genotypes with code==2 and call those with code==3 the BB genotypes.

If, instead, there are more genotypes with code 2 than code 3, we omit the genotypes with code==3 and call those with code==2 the BB genotypes.

Value

The input cross object, with genotype codes possibly changed and cross type changed to "risib".

Author(s)

Karl W Broman, [email protected]

See Also

convert2riself

Examples

data(hyper)
hyper.as.risib <- convert2risib(hyper)

Convert a sex-specific map to a sex-averaged one

Description

Convert a sex-specific map to a sex-averaged one, assuming that the female and male maps are actually the same (that is, that the map was estimated assuming a common recombination rate in females and males).

Usage

convert2sa(map, tol=1e-4)

Arguments

map

A map object with sex-specific locations (but assuming that the female and male maps are the same), as output by the function est.map for a 4-way cross, with argument sex.sp=FALSE.

tol

Tolerance value for inspecting the differences between the female and male maps; if they differ by more than this tolerance, a warning is issued.

Details

We pull out just the female marker locations, and give a warning if there are large differences between the female and male maps.

Value

A map object, with sex-averaged distances.

Author(s)

Karl W Broman, [email protected]

See Also

est.map, plotMap

Examples

data(fake.4way)
## Not run: fake.4way <- subset(fake.4way, chr="-X")

nm <- est.map(fake.4way, sex.sp=FALSE)
plot(convert2sa(nm))

Count number of obligate crossovers for each individual

Description

Count the number of obligate crossovers for each individual in a cross, either by chromosome or overall.

Usage

countXO(cross, chr, bychr=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to investigate. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

bychr

If TRUE, return counts for each individual chromosome; if FALSE, return the overall number across the selected chromosomes.

Details

For each individual we count the minimal number of crossovers that explain the observed genotype data.

Value

If bychr=TRUE, a matrix of counts is returned, with rows corresponding to individuals and columns corresponding to chromosomes.

If bychr=FALSE, a vector of counts (the total number of crossovers across all selected chromosomes) is returned.

Author(s)

Karl W Broman, [email protected]

See Also

ripple, locateXO, cleanGeno

Examples

data(hyper)
plot(countXO(hyper))

Drop duplicate markers

Description

Drop markers with duplicate names; retaining the first of each set, with consensus genotyps

Usage

drop.dupmarkers(cross, verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

verbose

If TRUE, print information on the numbers of genotypes and markers omitted. If > 1, give more detailed information on genotypes omitted.

Value

The input cross object, with any duplicate markers omitted (except for one). The marker retained will have consensus genotypes; if multiple versions of a marker have different genotypes for an individual, they will be replaced by NA.

Any derived data (such as produced by calc.genoprob) will be stripped off.

Author(s)

Karl W Broman, [email protected]

See Also

drop.nullmarkers, pull.markers, drop.markers, summary.cross, clean.cross

Examples

data(listeria)

listeria <- drop.dupmarkers(listeria)

Drop a set of markers

Description

Drop a vector of markers from the data matrices and genetic maps.

Usage

drop.markers(cross, markers)

Arguments

cross

An object of class cross. See read.cross for details.

markers

A character vector of marker names.

Value

The input object, with any markers in the vector markers removed from the genotype data matrices, genetic maps, and, if applicable, any derived data (such as produced by calc.genoprob). (It might be a good idea to re-derive such things after using this function.)

Author(s)

Karl W Broman, [email protected]

See Also

drop.nullmarkers, pull.markers, geno.table, clean.cross

Examples

data(listeria)
listeria2 <- drop.markers(listeria, c("D10M44","D1M3","D1M75"))

Drop markers without any genotype data

Description

Drop markers, from the data matrices and genetic maps, that have no genotype data.

Usage

drop.nullmarkers(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Value

The input object, with any markers lacking genotype data removed from the genotype data matrices, genetic maps, and, if applicable, any derived data (such as produced by calc.genoprob). (It might be a good idea to re-derive such things after using this function.)

Author(s)

Karl W Broman, [email protected]

See Also

nullmarkers, drop.markers, clean.cross, geno.table

Examples

# removes one marker from hyper
data(hyper)
hyper <- drop.nullmarkers(hyper)

# shouldn't do anything to listeria
data(listeria)
listeria <- drop.nullmarkers(listeria)

Drop a QTL from a qtl object

Description

Drop a QTL or multiple QTL from a QTL object

Usage

dropfromqtl(qtl, index, chr, pos, qtl.name, drop.lod.profile=TRUE)

Arguments

qtl

A qtl object, as created by makeqtl.

index

Vector specifying the numeric indices of the QTL to be dropped.

chr

Vector indicating the chromosome for each QTL to drop.

pos

Vector (of same length as chr) indicating the positions of the QTL to be dropped.

qtl.name

Vector specifying the names of the QTL to be dropped.

drop.lod.profile

If TRUE, remove any LOD profiles from the object.

Details

Provide either chr and pos, or one of qtl.name or index.

Value

The input qtl object with the specified QTL omitted. See makeqtl for details on the format.

Author(s)

Karl W Broman, [email protected]

See Also

makeqtl, fitqtl, addtoqtl, replaceqtl , reorderqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 6, 13)
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

newqtl <- dropfromqtl(qtl, chr=1, pos=25.8)
altqtl <- dropfromqtl(qtl, index=1)

Drop one marker at a time and determine effect on genetic map

Description

Drop one marker at a time from a genetic map and calculate the change in log likelihood and in the chromosome length, in order to identify problematic markers.

Usage

droponemarker(cross, chr, error.prob=0.0001,
                map.function=c("haldane","kosambi","c-f","morgan"),
                m=0, p=0, maxit=4000, tol=1e-6, sex.sp=TRUE,
                verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

A vector specifying which chromosomes to test for the position of the marker. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions. (Ignored if m > 0.)

m

Interference parameter for the chi-square model for interference; a non-negative integer, with m=0 corresponding to no interference. This may be used only for a backcross or intercross.

p

Proportion of chiasmata from the NI mechanism, in the Stahl model; p=0 gives a pure chi-square model. This may be used only for a backcross or intercross.

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

verbose

If TRUE, print information on progress; if > 1, print even more information.

Value

A data frame (actually, an object of class "scanone", so that one may use plot.scanone, summary.scanone, etc.) with each row being a marker. The first two columns are the chromosome ID and position. The third column is a LOD score comparing the hypothesis that the marker is not linked to the hypothesis that it belongs at that position.

In the case of a 4-way cross, with sex.sp=TRUE, there are two additional columns with the change in the estimated female and male genetic lengths of the respective chromosome, upon deleting that marker. With sex.sp=FALSE, or for other types of crosses, there is one additional column, with the change in estimated genetic length of the respective chromosome, when the marker is omitted.

A well behaved marker will have a negative LOD score and a small change in estimated genetic length. A poorly behaved marker will have a large positive LOD score and a large change in estimated genetic length. But note that dropping the first or last marker on a chromosome could result in a large change in estimated length, even if they are not badly behaved; for these markers one should focus on the LOD scores, with a large positive LOD score being bad.

Author(s)

Karl W Broman, [email protected]

See Also

tryallpositions, est.map, ripple, est.rf, switch.order, movemarker, drop.markers

Examples

data(fake.bc)
droponemarker(fake.bc, 7, error.prob=0, verbose=FALSE)

Plot phenotype means against genotypes at one or two markers

Description

Plot the phenotype means for each group defined by the genotypes at one or two markers (or the values at a discrete covariate).

Usage

effectplot(cross, pheno.col=1, mname1, mark1, geno1, mname2, mark2,
           geno2, main, ylim, xlab, ylab, col, add.legend=TRUE,
           legend.lab, draw=TRUE, var.flag=c("pooled","group"))

Arguments

cross

An object of class cross.

pheno.col

Column number in the phenotype matrix to be drawn in the plot. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

mname1

Name for the first marker or pseudomarker. Pseudomarkers (that is, non-marker positions on the imputation grid) may be referred to in a form like "[email protected]", for position 30.3 on chromosome 5.

mark1

Genotype data for the first marker. If unspecified, genotypes will be taken from the data in the input cross object, using the name specified in mname1.

geno1

Optional labels for the genotypes (or classes in a covariate).

mname2

Name for the second marker or pseudomarker (optional).

mark2

Like mark1 (optional).

geno2

Optional labels for the genotypes (or classes in a covariate).

main

Optional figure title.

ylim

Optional y-axis limits.

xlab

Optional x-axis label.

ylab

Optional y-axis label.

col

Optional vector of colors for the different line segments.

add.legend

A logical value to indicate whether to add a legend.

legend.lab

Optional title for the legend.

draw

A logical value to indicate generate the plot or not. If FALSE, no figure will be plotted and this function can be used to calculate the group means and standard errors.

var.flag

The method to calculate the group variance. "pooled" means to use the pooled variance and "group" means to calculate from individual group.

Details

In the plot, the y-axis is the phenotype. In the case of one marker, the x-axis is the genotype for that marker. In the case of two markers, the x-axis is for different genotypes of the second marker, and the genotypes of first marker are represented by lines in different colors. Error bars are plotted at ±\pm 1 SE.

The results of sim.geno are used; if they are not available, sim.geno is run with n.draws=16. The average phenotype for each genotype group takes account of missing genotype data by averaging across the imputations. The SEs take account of both the residual phenotype variation and the imputation error.

Value

A data.frame containing the phenotype means and standard errors for each group.

Author(s)

Hao Wu; Karl W Broman, [email protected]

See Also

plotPXG, find.marker, effectscan, find.pseudomarker

Examples

data(fake.f2)


# impute genotype data
## Not run: fake.f2 <- sim.geno(fake.f2, step=5, n.draws=64)


########################################
# one marker plots
########################################
### plot of genotype-specific phenotype means for 1 marker
mname <- find.marker(fake.f2, 1, 37) # marker D1M437
effectplot(fake.f2, pheno.col=1, mname1=mname)

### output of the function contains the means and SEs
output <- effectplot(fake.f2, mname1=mname)
output

### plot a phenotype
# Plot of sex-specific phenotype means,
# note that "sex" must be a phenotype name here
effectplot(fake.f2, mname1="sex", geno1=c("F","M"))
# alternatively:
sex <- pull.pheno(fake.f2, "sex")
effectplot(fake.f2, mname1="Sex", mark1=sex, geno1=c("F","M"))

########################################
# two markers plots
########################################

### plot two markers
# plot of genotype-specific phenotype means for 2 markers
mname1 <- find.marker(fake.f2, 1, 37) # marker D1M437
mname2 <- find.marker(fake.f2, 13, 24) # marker D13M254
effectplot(fake.f2, mname1=mname1, mname2=mname2)

### plot two pseudomarkers
#####  refer to pseudomarkers by their positions
effectplot(fake.f2, mname1="1@35", mname2="13@25")

#####  alternatively, find their names via find.pseudomarker
pmnames <- find.pseudomarker(fake.f2, chr=c(1, 13), c(35, 25))
effectplot(fake.f2, mname1=pmnames[1], mname2=pmnames[2])

### Plot of sex- and genotype-specific phenotype means
mname <- find.marker(fake.f2, 13, 24) # marker D13M254
# sex and a marker
effectplot(fake.f2, mname1=mname, mname2="Sex",
           mark2=sex, geno2=c("F","M"))

# Same as above, switch role of sex and the marker
# sex and marker
effectplot(fake.f2, mname1="Sex", mark1=sex,
           geno1=c("F","M"), mname2=mname)

# X chromosome marker
mname <- find.marker(fake.f2, "X", 14) # marker DXM66
effectplot(fake.f2, mname1=mname)

# Two markers, including one on the X
mnames <- find.marker(fake.f2, c(13, "X"), c(24, 14))
effectplot(fake.f2, mname1=mnames[1], mname2=mnames[2])

Plot estimated QTL effects across the whole genome

Description

This function is used to plot the estimated QTL effects along selected chromosomes. For a backcross, there will be only one line, representing the additive effect. For an intercross, there will be two lines, representing the additive and dominance effects.

Usage

effectscan(cross, pheno.col=1, chr, get.se=FALSE, draw=TRUE,
           gap=25, ylim, mtick=c("line","triangle"),
           add.legend=TRUE, alternate.chrid=FALSE, ...)

Arguments

cross

An object of class cross.

pheno.col

Column number in the phenotype matrix which to be drawn in the plot. One may also give a character string matching a phenotype name.

chr

Optional vector indicating the chromosomes to be drawn in the plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

get.se

If TRUE, estimated standard errors are calculated.

draw

If TRUE, draw the figure.

gap

Gap separating chromosomes (in cM).

ylim

Y-axis limits (optional).

mtick

Tick mark type for markers.

add.legend

If TRUE, add a legend.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

...

Passed to the function plot when it is called.

Details

The results of sim.geno are required for taking account of missing genotype information.

For a backcross, the additive effect is estimated as the difference between the phenotypic averages for heterozygotes and homozygotes.

For recombinant inbred lines, the additive effect is estimated as half the difference between the phenotypic averages for the two homozygotes.

For an intercross, the additive and dominance effects are estimated from linear regression on aa and dd with aa = -1, 0, 1, for the AA, AB and BB genotypes, respectively, and dd = 0, 1, 0, for the AA, AB and BB genotypes, respectively.

As usual, the X chromosome is a bit more complicated. We estimate separate additive effects for the two sexes, and for the two directions within females.

There is an internal function plot.effectscan that creates the actual plot by calling plot.scanone. In the case get.se=TRUE, colored regions indicate ±\pm 1 SE.

Value

The results are returned silently, as an object of class "effectscan", which is the same as the form returned by the function scanone, though with estimated effects where LOD scores might be. That is, it is a data frame with the first two columns being chromosome ID and position (in cM), and subsequent columns being estimated effects, and (if get.se=TRUE) standard errors.

Author(s)

Karl W. Broman, [email protected]

References

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

effectplot, plotPXG, sim.geno

Examples

data(fake.f2)

fake.f2 <- sim.geno(fake.f2, step=2.5, n.draws=16)

# allelic effect on whole genome
effectscan(fake.f2)

# on chromosome 13, include standard errors
effectscan(fake.f2, chr="13", mtick="triangle", get.se=TRUE)

Estimate genetic maps

Description

Uses the Lander-Green algorithm (i.e., the hidden Markov model technology) to re-estimate the genetic map for an experimental cross.

Usage

est.map(cross, chr, error.prob=0.0001,
        map.function=c("haldane","kosambi","c-f","morgan"),
        m=0, p=0, maxit=10000, tol=1e-6, sex.sp=TRUE,
        verbose=FALSE, omit.noninformative=TRUE, offset, n.cluster=1)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions. (Ignored if m > 0.)

m

Interference parameter for the chi-square model for interference; a non-negative integer, with m=0 corresponding to no interference. This may be used only for a backcross or intercross.

p

Proportion of chiasmata from the NI mechanism, in the Stahl model; p=0 gives a pure chi-square model. This may be used only for a backcross or intercross.

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

verbose

If TRUE, print tracing information.

omit.noninformative

If TRUE, on each chromosome, omit individuals with fewer than two typed markers, since they are not informative for linkage.

offset

Defines the starting position for each chromosome. If missing, we use the starting positions that are currently present in the input cross object. This should be a single value (to be used for all chromosomes) or a vector with length equal to the number of chromosomes, defining individual starting positions for each chromosome. For a sex-specific map (as in a 4-way cross), we use the same offset for both the male and female maps.

n.cluster

If the package snow is available calculations for multiple chromosomes are run in parallel using this number of nodes.

Details

By default, the map is estimated assuming no crossover interference, but a map function is used to derive the genetic distances (though, by default, the Haldane map function is used).

For a backcross or intercross, inter-marker distances may be estimated using the Stahl model for crossover interference, of which the chi-square model is a special case.

In the chi-square model, points are tossed down onto the four-strand bundle according to a Poisson process, and every (m+1)(m+1)st point is a chiasma. With the assumption of no chromatid interference, crossover locations on a random meiotic product are obtained by thinning the chiasma process. The parameter mm (a non-negative integer) governs the strength of crossover interference, with m=0m=0 corresponding to no interference.

In the Stahl model, chiasmata on the four-strand bundle are a superposition of chiasmata from two mechanisms, one following a chi-square model and one exhibiting no interference. An additional parameter, pp, gives the proportion of chiasmata from the no interference mechanism.

Value

A map object; a list whose components (corresponding to chromosomes) are either vectors of marker positions (in cM) or matrices with two rows of sex-specific marker positions. The maximized log likelihood for each chromosome is saved as an attribute named loglik. In the case that estimation was under an interference model (with m > 0), allowed only for a backcross, m and p are also included as attributes.

Author(s)

Karl W Broman, [email protected]

References

Armstrong, N. J., McPeek, M. J. and Speed, T. P. (2006) Incorporating interference into linkage analysis for experimental crosses. Biostatistics 7, 374–386.

Lander, E. S. and Green, P. (1987) Construction of multilocus genetic linkage maps in humans. Proc. Natl. Acad. Sci. USA 84, 2363–2367.

Lange, K. (1999) Numerical analysis for statisticians. Springer-Verlag. Sec 23.3.

Rabiner, L. R. (1989) A tutorial on hidden Markov models and selected applications in speech recognition. Proceedings of the IEEE 77, 257–286.

Zhao, H., Speed, T. P. and McPeek, M. S. (1995) Statistical analysis of crossover interference using the chi-square model. Genetics 139, 1045–1056.

See Also

map2table, plotMap, replace.map, est.rf, fitstahl

Examples

data(fake.f2)

newmap <- est.map(fake.f2)
logliks <- sapply(newmap, attr, "loglik")
plotMap(fake.f2, newmap)
fake.f2 <- replace.map(fake.f2, newmap)

Estimate pairwise recombination fractions

Description

Estimate the sex-averaged recombination fraction between all pairs of genetic markers.

Usage

est.rf(cross, maxit=10000, tol=1e-6)

Arguments

cross

An object of class cross. See read.cross for details.

maxit

Maximum number of iterations for the EM algorithm (not used with backcrosses).

tol

Tolerance for determining convergence (not used with backcrosses).

Details

For a backcross, one can simply count recombination events. For an intercross or 4-way cross, a version of the EM algorithm must be used to estimate recombination fractions. (Since, for example, in an intercross individual that is heterozygous at two loci, it is not known whether there were 0 or 2 recombination events.) Note that, for the 4-way cross, we estimate sex-averaged recombination fractions.

Value

The input cross object is returned with a component, rf, added. This is a matrix of size (tot.mar x tot.mar). The diagonal contains the number of typed meioses per marker, the lower triangle contains the estimated recombination fractions, and the upper triangle contains the LOD scores (testing rf = 0.5).

Author(s)

Karl W Broman, [email protected]

See Also

plotRF, pull.rf, plot.rfmatrix, est.map, badorder, checkAlleles

Examples

data(badorder)
badorder <- est.rf(badorder)
plotRF(badorder)

Simulated data for a 4-way cross

Description

Simulated data for a phase-known 4-way cross, obtained using sim.cross.

Usage

data(fake.4way)

Format

An object of class cross. See read.cross for details.

Details

There are 250 individuals typed at 157 markers, including 8 on the X chromosome.

There are two phenotypes (including sex, for which 0=female and 1=male). The quantitative phenotype is affected by three QTLs: two on chromosome 2 at positions 10 and 25 cM on the female genetic map, and one on chromosome 7 at position 40 cM on the female map.

Author(s)

Karl W Broman, [email protected]

See Also

sim.cross, fake.bc, fake.f2, listeria, hyper, bristle3, bristleX

Examples

data(fake.4way)

plot(fake.4way)
summary(fake.4way)

# estimate recombination fractions
fake.4way <- est.rf(fake.4way)
plotRF(fake.4way)

# estimate genetic maps
ssmap <- est.map(fake.4way, verbose=TRUE)
samap <- est.map(fake.4way, sex.sp=FALSE, verbose=TRUE)
plot(ssmap, samap)

# error lod scores
fake.4way <- calc.genoprob(fake.4way, err=0.01)
fake.4way <- calc.errorlod(fake.4way, err=0.01)
top.errorlod(fake.4way, cutoff=2.5)

# genome scan
fake.4way <- calc.genoprob(fake.4way, step=2.5)
out.hk <- scanone(fake.4way, method="hk")
out.em <- scanone(fake.4way, method="em")
plot(out.em,out.hk,chr=c(2,7))

Simulated data for a backcross

Description

Simulated data for a backcross, obtained using sim.cross.

Usage

data(fake.bc)

Format

An object of class cross. See read.cross for details.

Details

There are 400 backcross individuals typed at 91 markers and with two phenotypes and two covariates (sex and age).

The two phenotypes are due to four QTLs, with no epistasis. There is one on chromosome 2 (at 30 cM), two on chromosome 5 (at 10 and 50 cM), and one on chromosome 10 (at 30 cM). The QTL on chromosome 2 has an effect only in the males (sex=1); the two QTLs on chromosome 5 have effect in coupling for the first phenotype and in repulsion for the second phenotype. Age has an effect of increasing the phenotypes.

Author(s)

Karl W Broman, [email protected]

See Also

sim.cross, fake.4way, fake.f2, listeria, hyper, bristle3, bristleX

Examples

data(fake.bc)

summary(fake.bc)
plot(fake.bc)

# genome scans without covariates
fake.bc <- calc.genoprob(fake.bc, step=2.5)
out.nocovar <- scanone(fake.bc, pheno.col=1:2)

# genome scans with covariates
ac <- pull.pheno(fake.bc, c("sex","age"))
ic <- pull.pheno(fake.bc, "sex")
out.covar <- scanone(fake.bc, pheno.col=1:2,
                      addcovar=ac, intcovar=ic)

# summaries
summary(out.nocovar, thr=3, format="allpeaks")
summary(out.covar, thr=3, format="allpeaks")

# plots
plot(out.nocovar, out.covar, chr=c(2,5,10), lod=1, col="blue",
     lty=1:2, ylim=c(0,13))
plot(out.nocovar, out.covar, chr=c(2,5,10), lod=2, col="red",
     lty=1:2, add=TRUE)

Simulated data for an F2 intercross

Description

Simulated data for an F2 intercross, obtained using sim.cross.

Usage

data(fake.f2)

Format

An object of class cross. See read.cross for details.

Details

There are 200 F2 individuals typed at 94 markers, including 3 on the X chromosome. There is one quantitative phenotype, along with an indication of sex (0=female, 1=male) and the direction of the cross (pgm = paternal grandmother, 0=A, meaning the cross was (AxB)x(AxB), and 1=B, meaning the cross was (AxB)x(BxA)).

Note that the X chromosome genotypes are coded in a special way (see read.cross). For the individuals with pgm=0, sex=0, 1=AA and 2=AB; for individuals with pgm=0, sex=1, 1=A and 2=B (hemizygous); for individuals with pgm=1, sex=0, 1=BB and 2=AB; for individuals with pgm=1, sex=1, 1=A and 2=B. This requires special care!

The data were simulated using an additive model with three QTLs on chromosome 1 (at 30, 50 and 70 cM), one QTL on chromosome 13 (at 30 cM), and one QTL on the X chromosome (at 10 cM).

Author(s)

Karl W Broman, [email protected]

See Also

sim.cross, fake.bc, fake.4way, listeria, hyper, bristle3, bristleX

Examples

data(fake.f2)
summary(fake.f2)
plot(fake.f2)

Fill holes in genotype data

Description

Replace the genotype data for a cross with a version imputed either by simulation with sim.geno, by the Viterbi algorithm with argmax.geno, or simply filling in genotypes between markers that have matching genotypes.

Usage

fill.geno(cross, method=c("imp","argmax", "no_dbl_XO", "maxmarginal"),
          error.prob=0.0001,
          map.function=c("haldane","kosambi","c-f","morgan"),
          min.prob=0.95)

Arguments

cross

An object of class cross. See read.cross for details.

method

Indicates whether to impute using a single simulation replicate from sim.geno, using the Viterbi algorithm, as implemented in argmax.geno, by simply filling in missing genotypes between markers with matching genotypes, or by choosing (at each marker) the genotype with maximal marginal probability.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi or Carter-Falconer map function when converting genetic distances into recombination fractions.

min.prob

For method="maxmarginal", genotypes with probability greater than this value will be imputed; those less than this value will be made missing.

Details

This function is written so that one may perform rough genome scans by marker regression without having to drop individuals with missing genotype data. We must caution the user that little trust should be placed in the results.

With method="imp", a single random imputation is performed, using sim.geno.

With method="argmax", for each individual the most probable sequence of genotypes, given the observed data (via argmax.geno), is used.

With method="no_dbl_XO", non-recombinant intervals are filled in; recombinant intervals are left missing. For example, a sequence of genotypes like A---A---H---H---A (with A and H corresponding to genotypes AA and AB, respectively, and with - being a missing value) will be filled in as AAAAA---HHHHH---A.

With method="maxmarginal", the conditional genotype probabilities are calculated with calc.genoprob, and then at each marker, the most probable genotype is determined. This is taken as the imputed genotype if it has probability greater than min.prob; otherwise it is made missing.

With method="no_dbl_XO" and method="maxmarginal", some missing genotypes likely remain. With method="maxmarginal", some observed genotypes may be made missing.

Value

The input cross object with the genotype data replaced by an imputed version. Any intermediate calculations (such as is produced by calc.genoprob, argmax.geno and sim.geno) are removed.

Author(s)

Karl W Broman, [email protected]

See Also

sim.geno, argmax.geno

Examples

data(hyper)

out.mr <- scantwo(fill.geno(hyper,method="argmax"), method="mr")
plot(out.mr)

Find large intervals in a map

Description

Find large inter-marker intervals in a map.

Usage

find_large_intervals(map, min_length=35)

Arguments

map

A list of numeric vectors; each component is a chromosome with the positions of markers on that chromosome. Can also be an object of class cross, in which case pull.map is used.

min_length

Minimum length of interval to be flagged.

Value

Data frame with chromosome, left and right markers and interval length.

Author(s)

Karl W Broman, [email protected]

See Also

summaryMap

Examples

data(fake.f2)

find_large_intervals(fake.f2, 30)

Find flanking markers for a specified position

Description

Find the genetic markers flanking a specified position on a chromosome, as well as the marker that is closest to the specified position.

Usage

find.flanking(cross, chr, pos)

Arguments

cross

An object of class cross. See read.cross for details.

chr

A vector of chromosome identifiers, or a single such.

pos

A vector of cM positions.

Value

A data.frame, each row corresponding to one of the input positions. The first column contains the left-flanking markers, the second column contains the right-flanking markers, and the third column contains the markers closest to the specified positions.

Author(s)

Brian Yandell

See Also

find.marker, plotPXG, find.markerpos, find.pseudomarker

Examples

data(listeria)
find.flanking(listeria, 5, 28)
find.flanking(listeria, c(1, 5, 13), c(81, 28, 26))

Find marker closest to a specified position

Description

Find the genetic marker closest to a specified position on a chromosome.

Usage

find.marker(cross, chr, pos, index)

Arguments

cross

An object of class cross. See read.cross for details.

chr

A vector of chromosome identifiers, or a single such.

pos

A vector of cM positions.

index

A vector of numeric indices of the markers within chromosomes.

Details

Provide one of pos or index.

If the input chr has length one, it is expanded to the same length as the input pos or index.

If pos is specified and multiple markers are exactly the same distance from the specified position, one is chosen at random from among those with the most genotype data.

For a cross with sex-specific maps, positions specified by pos are assumed to correspond to the female genetic map.

Value

A vector of marker names (of the same length as the input pos), corresponding to the markers nearest to the specified chromosomes/positions (if pos is specified) or to the input numeric indices (in index is specified).

Author(s)

Karl W Broman, [email protected]

See Also

find.flanking, plotPXG, find.pseudomarker, effectplot, find.markerpos

Examples

data(listeria)
find.marker(listeria, 5, 28)
find.marker(listeria, 5, index=6)
find.marker(listeria, c(1, 5, 13), c(81, 28, 26))

Determine the numeric index for a marker

Description

Determine the numeric index for a marker in a cross object, when all markers on all chromosomes are pasted together.

Usage

find.markerindex(cross, name)

Arguments

cross

An object of class cross. See read.cross for details.

name

A vector of marker names.

Value

A vector of numeric indices, from 1, 2, ..., totmar(cross), with NA for markers not found.

Author(s)

Danny Arends; Karl W Broman [email protected]

See Also

find.markerpos

Examples

data(hyper)
mar <- find.marker(hyper, 4, 30)
find.markerindex(hyper, mar)

Find position of a marker

Description

Find the chromosome and cM position of a set of genetic markers.

Usage

find.markerpos(cross, marker)

Arguments

cross

An object of class cross. See read.cross for details.

marker

A vector of marker names.

Value

A data frame with two columns: the chromosome and position of the markers.

Author(s)

Karl W Broman, [email protected]

See Also

find.flanking, find.marker, find.pseudomarker

Examples

data(hyper)
find.markerpos(hyper, "D4Mit164")
find.markerpos(hyper, c("D4Mit164", "D1Mit94"))

Find column number for a particular phenotype

Description

Find the column number corresponding to a particular phenotype name.

Usage

find.pheno(cross, pheno)

Arguments

cross

An object of class cross. See read.cross for details.

pheno

Vector of phenotype names (as character strings).

Value

A vector of numbers, corresponding to the column numbers of the phenotype in the input cross with the specified names.

Author(s)

Brian Yandell

Examples

data(fake.bc)
find.pheno(fake.bc, "sex")

Find the pseudomarker closest to a specified position

Description

Find the pseudomarker closest to a specified position on a chromosome.

Usage

find.pseudomarker(cross, chr, pos, where=c("draws", "prob"), addchr=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

A vector of chromosome identifiers, or a single such.

pos

A vector of cM positions.

where

Indicates whether to look in the draws or prob components of the input cross.

addchr

If TRUE, include something like "c5." at the beginning of the names of non-pseudomarker locations, as in the output of scanone; if FALSE, don't include this sort of string, as in the genotype probabilities from calc.genoprob.

Details

If the input chr has length one, it is expanded to the same length as the input pos.

If multiple markers are exactly the same distance from the specified position, one is chosen at random from among those with the most genotype data.

For a cross with sex-specific maps, the input positions are assumed to correspond to the female genetic map.

Value

A vector of pseudomarker names (of the same length as the input pos), corresponding to the markers nearest to the specified chromosomes/positions.

Author(s)

Karl W Broman, [email protected]

See Also

find.flanking, plotPXG, effectplot, find.marker, find.markerpos

Examples

data(listeria)
listeria <- calc.genoprob(listeria, step=2.5)
find.pseudomarker(listeria, 5, 28, "prob")
find.pseudomarker(listeria, c(1, 5, 13), c(81, 28, 26), "prob")

Find markers with identical genotype data

Description

Identify sets of markers with identical genotype data.

Usage

findDupMarkers(cross, chr, exact.only=TRUE, adjacent.only=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector specifying which chromosomes to consider. This may be a logical, numeric, or character string vector.

exact.only

If TRUE, look only for markers that have matching genotypes and the same pattern of missing data; if FALSE, also look for cases where the observed genotypes at one marker match those at another, and where the first marker has missing genotype whenever the genotype for the second marker is missing.

adjacent.only

If TRUE, look only for sets of markers that are adjacent to each other.

Details

If exact.only=TRUE, we look only for groups of markers whose pattern of missing data and observed genotypes match exactly. One marker (chosen at random) is selected as the name of the group (in the output of the function).

If exact.only=FALSE, we look also for markers whose observed genotypes are contained in the observed genotypes of another marker. We use a pair of nested loops, working from the markers with the most observed genotypes to the markers with the fewest observed genotypes.

Value

A list of marker names; each component is a set of markers whose genotypes match one other marker, and the name of the component is the name of the marker that they match.

Author(s)

Karl W Broman, [email protected]

See Also

drop.nullmarkers, drop.markers, pickMarkerSubset

Examples

data(hyper)

hyper <- drop.nullmarkers(hyper)

dupmar <- findDupMarkers(hyper) # finds 4 pairs
dupmar.adjonly <- findDupMarkers(hyper, adjacent.only=TRUE) # finds 4 pairs

dupmar.nexact <- findDupMarkers(hyper, exact.only=FALSE, adjacent.only=TRUE) # finds 6 pairs

# one might consider dropping the extra markers
totmar(hyper) # 173 markers
hyper <- drop.markers(hyper, unlist(dupmar.adjonly))
totmar(hyper) # 169 markers

Fit a multiple-QTL model

Description

Fits a user-specified multiple-QTL model. If specified, a drop-one-term analysis will be performed.

Usage

fitqtl(cross, pheno.col=1, qtl, covar=NULL, formula, method=c("imp", "hk"),
       model=c("normal", "binary"), dropone=TRUE, get.ests=FALSE,
       run.checks=TRUE, tol=1e-4, maxit=1000, forceXcovar=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

An object of class qtl, as output from makeqtl.

covar

A matrix or data.frame of covariates. These must be strictly numeric.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are referred to as Q1, Q2, etc. Covariates are referred to by their names in the data frame covar.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

dropone

If TRUE, do drop-one-term analysis.

get.ests

If TRUE, return estimated QTL effects and their estimated variance-covariance matrix.

run.checks

If TRUE, check the input formula and check for individuals with missing phenotypes or covariates.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

forceXcovar

If TRUE, force inclusion of X-chr-related covariates (like sex and cross direction).

Details

The formula is used to specified the model to be fit. In the formula, use Q1, Q2, etc., or q1, q2, etc., to represent the QTLs, and the column names in the covariate data frame to represent the covariates.

We enforce a hierarchical structure on the model formula: if a QTL or covariate is in involved in an interaction, its main effect must also be included.

In the drop-one-term analysis, for a given QTL/covariate model, all submodels will be analyzed. For each term in the input formula, when it is dropped, all higher order terms that contain it will also be dropped. The comparison between the new model and the full (input) model will be output.

The estimated percent variances explained for the QTL are simply transformations of the conditional LOD scores by the formula h2=110(2/n)LODh^2 = 1 - 10^{-(2/n) {\rm LOD}}. While these may be reasonable for unlinked, additive QTL, they can be completely wrong in the case of linked QTL, but we don't currently have any alternative.

For model="binary", a logistic regression model is used.

The part to get estimated QTL effects is not complete for the case of the X chromosome and 4-way crosses. The values returned in these cases are based on a design matrix that is convenient for calculations but not easily interpreted.

The estimated QTL effects for a backcross are derived by the coding scheme ±\pm 1/2 for AA and AB, so that the additive effect corresponds to the difference between phenotype averages for the two genotypes. For doubled haploids and RIL, the coding scheme is ±\pm 1 for AA and BB, so that the additive effect corresponds to half the difference between the phenotype averages for the two homozygotes.

For an intercross, the additive effect is derived from the coding scheme -1/0/+1 for genotypes AA/AB/BB, and so is half the difference between the phenotype averages for the two homozygotes. The dominance deviation is derived from the coding scheme 0/+1/0 for genotypes AA/AB/BB, and so is the difference between the phenotype average for the heterozygotes and the midpoint between the phenotype averages for the two homozygotes.

Epistatic effects and QTL ×\times covariate interaction effects are obtained through the products of the corresponding additive/dominant effect columns.

Value

An object of class fitqtl. It may contains as many as four components:

  • result.full is the ANOVA table as a matrix for the full model result. It contains the degree of freedom (df), Sum of squares (SS), mean square (MS), LOD score (LOD), percentage of variance explained (%var) and P value (Pvalue).

  • lod is the LOD score from the fit of the full model.

  • result.drop is a drop-one-term ANOVA table as a matrix. It contains degrees of freedom (df), Type III sum of squares (Type III SS), LOD score(LOD), percentage of variance explained (%var), F statistics (F value), and P values for chi square (Pvalue(chi2)) and F distribution (Pvalue(F)). Note that the degree of freedom, Type III sum of squares, the LOD score and the percentage of variance explained are the values comparing the full to the sub-model with the term dropped. Also note that for imputation method, the percentage of variance explained, the the F values and the P values are approximations calculated from the LOD score.

  • ests contains the estimated QTL effects and standard errors.

When method="normal", residuals are saved as an attribute of the output, named "residuals" and accessible via the attr function.

The part to get estimated QTL effects is fully working only for the case of autosomes in a backcross, intercross, RIL or doubled haploids. In other cases the values returned are based on a design matrix that is convenient for calculations but not easily interpreted.

Author(s)

Hao Wu; Karl W Broman, [email protected]

References

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

summary.fitqtl, makeqtl, scanqtl, refineqtl, addtoqtl , dropfromqtl, replaceqtl, reorderqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 8, 13)
qp <- c(26, 56, 28)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

# fit model with 3 interacting QTLs interacting
# (performing a drop-one-term analysis)
lod <- fitqtl(fake.f2, pheno.col=1, qtl, formula=y~Q1*Q2*Q3, method="hk")
summary(lod)

## Not run: 
# fit an additive QTL model
lod.add <- fitqtl(fake.f2, pheno.col=1, qtl, formula=y~Q1+Q2+Q3, method="hk")
summary(lod.add)

# fit the model including sex as an interacting covariate
Sex <- data.frame(Sex=pull.pheno(fake.f2, "sex"))
lod.sex <- fitqtl(fake.f2, pheno.col=1, qtl, formula=y~Q1*Q2*Q3*Sex,
                  cov=Sex, method="hk")
summary(lod.sex)

# fit the same with an additive model
lod.sex.add <- fitqtl(fake.f2, pheno.col=1, qtl, formula=y~Q1+Q2+Q3+Sex,
                      cov=Sex, method="hk")
summary(lod.sex.add)

# residuals
residuals <- attr(lod.sex.add, "residuals")
plot(residuals)

## End(Not run)

Fit Stahl interference model

Description

Fit the Stahl model for crossover inference (or the chi-square model, which is a special case).

Usage

fitstahl(cross, chr, m, p, error.prob=0.0001, maxit=4000, tol=1e-4,
         maxm=15, verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

m

Interference parameter (a non-negative integer); if unspecified, this is estimated.

p

The proportion of chiasmata coming from the no interference mechanism in the Stahl model (0 <= p <= 1). p=0 gives the chi-square model. If unspecified, this is estimated.

error.prob

The genotyping error probability. If = NULL, it is estimated.

maxit

Maximum number of iterations to perform.

tol

Tolerance for determining convergence.

maxm

Maximum value of m to consider, if m is unspecified.

verbose

Logical; indicates whether to print tracing information.

Details

This function is currently only available for backcrosses and intercrosses.

The Stahl model of crossover interference (of which the chi-square model is a special case) is fit. In the chi-square model, points are tossed down onto the four-strand bundle according to a Poisson process, and every (m+1)(m+1)st point is a chiasma. With the assumption of no chromatid interference, crossover locations on a random meiotic product are obtained by thinning the chiasma process. The parameter mm (a non-negative integer) governs the strength of crossover interference, with m=0m=0 corresponding to no interference.

In the Stahl model, chiasmata on the four-strand bundle are a superposition of chiasmata from two mechanisms, one following a chi-square model and one exhibiting no interference. An additional parameter, pp, gives the proportion of chiasmata from the no interference mechanism.

If all of m, p, and error.prob are specified, any of them with length > 1 must all have the same length.

If m is unspecified, we do a grid search starting at 0 and stop when the likelihood decreases (thus assuming a single mode), or maxm is reached.

Value

A matrix with four columns: m, p, error.prob, and the log likelihood.

If specific values for m, p, error.prob are provided, the log likelihood for each set are given.

If some are left unspecified, the maximum likelihood estimates are provided in the results.

Author(s)

Karl W Broman, [email protected]

References

Armstrong, N. J., McPeek, M. J. and Speed, T. P. (2006) Incorporating interference into linkage analysis for experimental crosses. Biostatistics 7, 374–386.

Zhao, H., Speed, T. P. and McPeek, M. S. (1995) Statistical analysis of crossover interference using the chi-square model. Genetics 139, 1045–1056.

See Also

est.map, sim.cross

Examples

# Simulate genetic map: one chromosome of length 200 cM with
# a 2 cM marker spacing
mymap <- sim.map(200, 51, anchor.tel=TRUE, include.x=FALSE,
                 sex.sp=FALSE, eq.spacing=TRUE)

# Simulate data under the chi-square model, no errors
mydata <- sim.cross(mymap, n.ind=250, type="bc",
                    error.prob=0, m=3, p=0)

# Fit the chi-square model for specified m's
## Not run: output <- fitstahl(mydata, m=1:5, p=0, error.prob=0)

plot(output$m, output$loglik, lwd=2, type="b")

# Find the MLE of m in the chi-square model
## Not run: mle <- fitstahl(mydata, p=0, error.prob=0)

## Not run: 
# Simulate data under the Stahl model, no errors
mydata <- sim.cross(mymap, n.ind=250, type="bc",
                    error.prob=0, m=3, p=0.1)

# Find MLE of m for the Stahl model with known p
mle.stahl <- fitstahl(mydata, p=0.1, error.prob=0)

# Fit the Stahl model with unknown p and m,
# get results for m=0, 1, 2, ..., 8
output <- fitstahl(mydata, m=0:8, error.prob=0)
plot(output$m, output$loglik, type="b", lwd=2)
## End(Not run)

Flip the orders of markers on a set of chromosomes

Description

Flip the orders of markers on a specified set of chromosome, so that the markers will be in the reverse order.

Usage

flip.order(cross, chr)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Vector indicating the chromosomes to flip. This should be a vector of character strings referring to chromosomes by name. A logical (TRUE/FALSE) vector may also be used.

Details

If the cross contains results from calc.genoprob, sim.geno, argmax.geno, or calc.errorlod, those results are also updated.

Results of est.rf and markerlrt are deleted.

Value

The input cross object, but with the marker order on the specified chromosomes flipped.

Author(s)

Karl W Broman, [email protected]

See Also

switch.order

Examples

data(fake.f2)
fake.f2 <- flip.order(fake.f2, c(1, 5, 13))

Partition markers into linkage groups

Description

Use pairwise linkage information between markers (as calculated by est.rf to partition markers into linkage groups.

Usage

formLinkageGroups(cross, max.rf=0.25, min.lod=3, reorgMarkers=FALSE,
                  verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

max.rf

Maximum recombination fraction for placing two markers in the same linkage group (see Details).

min.lod

Minimum LOD score for placing two markers in the same linkage group (see Details).

reorgMarkers

If TRUE, the output is a cross object, like the input, but with the markers organized into the inferred linkage groups. If FALSE, the output is a table indicating the initial chromosome assignments and the inferred linkage group partitions.

verbose

If TRUE, display information about the progress of the calculations.

Details

Two markers are placed in the same linkage group if the estimated recombination fraction between them is \le max.rf and the LOD score (for the test of the rec. frac. = 1/2) is \ge min.lod. The transitive property (if A is linked to B and B is linked to C then A is linked to C) is used to close the groups.

Value

If reorgMarkers=FALSE (the default), the output is a data frame with rows corresponding to the markers and with two columns: the initial chromosome assignment and the inferred linkage group. Linkage groups are ordered by the number of markers they contain (from largest to smallest).

If reorgMarkers=TRUE, the output is a cross object, like the input, but with the markers reorganized into the inferred linkage groups. The marker order and marker positions within the linkage groups are arbitrary.

Author(s)

Karl W Broman, [email protected]

See Also

est.rf, orderMarkers

Examples

data(listeria)
listeria <- est.rf(listeria)
result <- formLinkageGroups(listeria)
tab <- table(result[,1], result[,2])
apply(tab, 1, function(a) sum(a!=0))
apply(tab, 2, function(a) sum(a!=0))

Create matrix of marker covariates for QTL analysis

Description

Pull out a matrix of genotypes or genotype probabilities to use markers as covariates in QTL analysis.

Usage

formMarkerCovar(cross, markers, method=c("prob", "imp", "argmax"), ...)

Arguments

cross

An object of class cross. See read.cross for details.

markers

A vector of character strings of marker or pseudomarker names. Pseudomarker names may be of the form "[email protected]" (for chr 5 at 21.5 cM), but then all names must be of this form.

method

If method="prob", the genotype probabilities from calc.genoprob are used; otherwise we use fill.geno to impute missing data, with this method.

...

Passed to fill.geno, if necessary.

Value

A matrix containing genotype probabilities or genotype indicators, suitable for use as covariates in scanone.

Author(s)

Karl W Broman, [email protected]

See Also

pull.geno, pull.genoprob, fill.geno, scanone

Examples

data(hyper)
hyper <- calc.genoprob(hyper, step=0)
peakMarker <- "D4Mit164"
X <- formMarkerCovar(hyper, peakMarker)

out <- scanone(hyper, addcovar=X)

Create table of two-locus genotypes

Description

Create a cross tabulation of the genotypes at a pair of markers.

Usage

geno.crosstab(cross, mname1, mname2, eliminate.zeros=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

mname1

The name of the first marker (as a character string). (Alternatively, a vector with the two character strings, in which case mname2 should not be given.)

mname2

The name of the second marker (as a character string).

eliminate.zeros

If TRUE, don't show the rows and columns that have no data.

Value

A matrix containing the number of individuals having each possible pair of genotypes. Genotypes for the first marker are in the rows; genotypes for the second marker are in the columns.

Author(s)

Karl W Broman, [email protected]

See Also

geno.table, find.marker

Examples

data(hyper)
geno.crosstab(hyper, "D1Mit123", "D1Mit156")
geno.crosstab(hyper, "DXMit22", "DXMit16")
geno.crosstab(hyper, c("DXMit22", "DXMit16"))

Plot grid of genotype data

Description

Plot a grid showing which the genotype data in a cross.

Usage

geno.image(x, chr, reorder=FALSE, main="Genotype data",
           alternate.chrid=FALSE, col=NULL, ...)

Arguments

x

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to be drawn in the plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

reorder

Specify whether to reorder individuals according to their phenotypes.

FALSE Don't reorder
TRUE Reorder according to the sum of the phenotypes
n Reorder according to phenotype n
main

Title to place on plot.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

col

Vector of colors. The first is for missing genotypes, followed by colors for each of the genotypes. If NULL, a default set of colors are used.

...

Passed to image.

Details

Uses image to plot a grid with the genotype data. The genotypes AA, AB, BB are displayed in the colors red, blue, and green, respectively. In an intercross, if there are genotypes "not BB" and "not AA", these are displayed in purple and orange, respectively. White pixels indicate missing data.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

plot.cross, plotMissing, plotGeno, image

Examples

data(listeria)
geno.image(listeria)

Create table of genotype distributions

Description

Create table showing the observed numbers of individuals with each genotype at each marker, including P-values from chi-square tests for Mendelian segregation.

Usage

geno.table(cross, chr, scanone.output=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

scanone.output

If TRUE, give result in the form output by scanone, so that one may use plot.scanone, etc.

Details

The P-values are obtained from chi-square tests of Mendelian segregation. In the case of the X chromosome, the sexes and cross directions are tested separately, and the chi-square statistics combined, and so the test is of whether any of the groups show deviation from Mendel's rules.

Value

If scanone.output=FALSE, the output is a matrix containing, for each marker, the number of individuals with each possible genotype, as well as the number that were not typed. The first column gives the chromosome ID, and the last column gives P-values from chi-square tests of Mendelian segregation.

If scanone.output=TRUE, the output is of the form produced by scanone, with the first two columns being chromosome IDs and cM positions of the markers. The third column is log10(P)-\log_{10}(P) from chi-square tests of Mendelian segregation. The fourth column is the proportion of missing data. The remaining columns are the proportions of the different genotypes (among typed individuals).

Author(s)

Karl W Broman, [email protected]

See Also

summary.cross, drop.markers, drop.nullmarkers

Examples

data(listeria)
geno.table(listeria)

geno.table(listeria, chr=13)

gt <- geno.table(listeria)
gt[gt$P.value < 0.01,]

out <- geno.table(listeria, scanone.output=TRUE)
plot(out)
plot(out, lod=2)

Pull out the individual identifiers from a cross

Description

Pull out the individual identifiers from a cross object.

Usage

getid(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Value

A vector of individual identifiers, pulled from the phenotype data (a column named id or ID).

If there are no such identifiers in the cross, the function returns NULL.

Author(s)

Karl W Broman, [email protected]

See Also

subset.cross, top.errorlod

Examples

data(fake.f2)

# create an ID column
fake.f2$pheno$id <- paste("ind", sample(nind(fake.f2)), sep="")

getid(fake.f2)

Retrieving groups of traits after clustering

Description

Retrieving groups of clustered traits from the output of mqmplot.clusteredheatmap.

Usage

groupclusteredheatmap(cross, clusteredheatmapresult, height)

Arguments

cross

An object of class cross. See read.cross for details.

clusteredheatmapresult

Resultint dendrogram object from mqmplot.clusteredheatmap

height

Height at which to 'cut' the dendrogram, a higher cut-off gives less but larger groups. Height represents the maximum distance between two traits clustered together using hclust. the 'normal' behaviour of bigger groups when using a higher heigh cut-off depends on the tree stucture and the amount of traits clustered using mqmplot.clusteredheatmap

Value

A list containing groups of traits which were clustered together with a distance less that height

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

multitrait <- fill.geno(multitrait) # impute missing genotype data
result <- mqmscanall(multitrait, logtransform=TRUE)
cresults <- mqmplot.clusteredheatmap(multitrait,result)
groupclusteredheatmap(multitrait,cresults,10)

Data on hypertension

Description

Data from an experiment on hypertension in the mouse.

Usage

data(hyper)

Format

An object of class cross. See read.cross for details.

Details

There are 250 male backcross individuals typed at 174 markers (actually one contains only missing values), including 4 on the X chromosome, with one phenotype.

The phenotype is the blood pressure. See the reference below. Note that, for most markers, genotypes are available on only the individuals with extreme phenotypes. At many markers, only recombinant individuals were typed.

Source

Bev Paigen and Gary Churchill (The Jackson Laboratory, Bar Harbor, Maine) https://phenome.jax.org/projects/Sugiyama2

References

Sugiyama, F., Churchill, G. A., Higgens, D. C., Johns, C., Makaritsis, K. P., Gavras, H. and Paigen, B. (2001) Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci. Genomics 71, 70–77.

See Also

fake.bc, fake.f2, fake.4way, listeria, bristle3, bristleX

Examples

data(hyper)
summary(hyper)
plot(hyper)

# Note the selective genotyping
## Not run: plotMissing(hyper, reorder=TRUE)

# A marker on c14 has no data; remove it
hyper <- drop.nullmarkers(hyper)

Crude reconstruction of founder haplotypes in multi-parent RIL

Description

Uses groups of adjacent markers to infer the founder haplotypes in SNP data on multi-parent recombinant inbred lines.

Usage

inferFounderHap(cross, chr, max.n.markers=15)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Indicator of chromosome to consider. If multiple chromosomes are selected, only the first is used.

max.n.markers

Maximum number of adjacent markers to consider.

Details

We omit SNPs for which any of the founders are missing.

We then consider groups of adjacent SNPs, looking for founder haplotypes that are unique; RIL sharing such a unique haplotype are then inferred to have that founder's DNA.

We consider each marker as the center of a haplotype, and consider haplotypes of size 1, 3, 5, ..., max.n.markers. We end the extension of the haplotypes when all founders have a unique haplotype.

Value

A matrix of dimension nind(cross) ×\times no. markers, with the inferred founder origin for each line at each marker.

Author(s)

Karl W Broman, [email protected]

See Also

sim.geno, calc.genoprob, fill.geno, argmax.geno

Examples

map <- sim.map(100, n.mar=101, include.x=FALSE, eq.spacing=TRUE)
founderGeno <- simFounderSnps(map, "8")
ril <- sim.cross(map, n.ind=10, type="ri8sib", founderGeno=founderGeno)

h <- inferFounderHap(ril, max.n.markers=11)
mean(!is.na(h)) # proportion inferred
plot(map[[1]], h[1,], ylim=c(0.5, 8.5), xlab="Position", ylab="Genotype")

Identify inferred partitions in mapping QTL to a phylogenetic tree

Description

Identify the inferred partitions for a chromosome from the results of scanPhyloQTL.

Usage

inferredpartitions(output, chr, lodthreshold, probthreshold=0.9)

Arguments

output

An object output by the function scanPhyloQTL.

chr

A character string indicating the chromosome to consider. (It can also be a number, but it's then converted to a character string.)

lodthreshold

LOD threshold; if maximum LOD score is less than this, the null model is considered.

probthreshold

Threshold on posterior probabilities. See Details below.

Details

We consider a single chromosome, and take the maximum LOD score for each partition on that chromosome. The presence of a QTL is inferred if at least one partition has LOD score greater than lodthreshold. In this case, we then convert the LOD scores for the partitions to approximate posterior probabilities by taking 10LOD10^{LOD} and then rescaling them to sum to 1. These are sorted from largest to smallest, and we then take as the inferred partitions the smallest set whose posterior probabilities cumulatively add up to at least probthreshold.

Value

A vector of character strings. If the null model (no QTL) is inferred, the output is "null". Otherwise, it is the set of inferred partitions.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Kim, S., An\'e, C. and Payseur, B. A. Mapping quantitative trait loci to a phylogenetic tree. In preparation.

See Also

scanPhyloQTL, plot.scanPhyloQTL, summary.scanPhyloQTL, max.scanPhyloQTL, simPhyloQTL

Examples

# example map; drop X chromosome
data(map10)
map10 <- map10[1:19]


# simulate data
x <- simPhyloQTL(4, partition="AB|CD", crosses=c("AB", "AC", "AD"),
                 map=map10, n.ind=150,
                 model=c(1, 50, 0.5, 0))

# run calc.genoprob on each cross
## Not run: x <- lapply(x, calc.genoprob, step=2)


# scan genome, at each position trying all possible partitions
out <- scanPhyloQTL(x, method="hk")

# inferred partitions
inferredpartitions(out, chr=3, lodthreshold=3)

# inferred partitions with prob'y threshold = 0.95
inferredpartitions(out, chr=3, lodthreshold=3, probthreshold=0.95)

Interpolate positions from one map to another

Description

On the basis of a pair of marker maps with common markers, take positions along one map and interpolate (or, past the terminal markers on a chromosome, extrapolate) their positions on the second map.

Usage

interpPositions(oldpositions, oldmap, newmap)

Arguments

oldpositions

A data frame with two columns: chr (chromosome identifiers) and pos (positions, along oldmap).

oldmap

An object of class "map"; see sim.map for details.

newmap

An object of class "map", with the same chromosomes and markers as oldmap.

Details

In this explanation, take oldmap and newmap to be the physical and genetic maps, respectively.

We use linear interpolation within each interval, assuming a constant recombination rate within the interval. Past the terminal markers, we use linear extrapolation, using the chromosome-wide average recombination rate.

Value

The input data frame, oldpositions, with an additional column newpos with the interpolated positions along newmap.

Author(s)

Karl W Broman, [email protected]

See Also

shiftmap, rescalemap, pull.map

Examples

data(hyper)

# hyper genetic map
gmap <- pull.map(hyper)

# a fake physical map, with each chromosome starting at 0.
pmap <- shiftmap(rescalemap(gmap, 2))

# positions on pmap to determine location on gmap
tofind <- data.frame(chr=c(1, 5, 17, "X"), pos=c(220, 20, 105, 10))
rownames(tofind) <- paste("loc", 1:nrow(tofind), sep="")

interpPositions(tofind, pmap, gmap)

Jitter marker positions in a genetic map

Description

Jitter the marker positions in a genetic map so that no two markers are on top of each other.

Usage

jittermap(object, amount=1e-6)

Arguments

object

Either a cross (an object of class cross; see read.cross for details) or a map (an object of class map; see pull.map for details).

amount

The amount by which markers should be moved.

Value

Either the input cross object or the input map, but with marker positions slightly jittered. If the input was a cross, the function clean is run to strip off any intermediate calculations.

Author(s)

Karl W Broman, [email protected]

See Also

pull.map, replace.map, summary.cross

Examples

data(hyper)
hyper <- jittermap(hyper)

Data on Listeria monocytogenes susceptibility

Description

Data from an experiment on susceptibility to Listeria monocytogenes infection in the mouse.

Usage

data(listeria)

Format

An object of class cross. See read.cross for details.

Details

There are 120 F2 individuals typed at 133 markers, including 2 on the X chromosome, with one phenotype.

The phenotype is the survival time (in hours) following infection. Mice with phenotype 264 hours may be considered to have recovered from the infection. See the references below.

Source

Victor Boyartchuk and William Dietrich (Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute)

References

Boyartchuk, V. L., Broman, K. W., Mosher, R. E., D'Orazio S. E. F., Starnbach, M. N. and Dietrich, W. F. (2001) Multigenic control of Listeria monocytogenes susceptibility in mice. Nature Genetics 27, 259–260.

Broman, K. W. (2003) Mapping quantitative trait loci in the case of a spike in the phenotype distribution. Genetics 163, 1169–1175.

See Also

fake.bc, fake.f2, fake.4way, hyper, bristle3, bristleX

Examples

data(listeria)

# Summaries
summary(listeria)
plot(listeria)

# Take log of phenotype
listeria$pheno[,1] <- log2(listeria$pheno[,1])
plot(listeria)

# Genome scan with a two-part model, using log survival
listeria <- calc.genoprob(listeria, step=2)
out <- scanone(listeria, model="2part", method="em",
               upper=TRUE)

# Summary of the results
summary(out, thr=c(5,3,3), format="allpeaks")

# Plot LOD curves for interesting chromosomes
#     (The two-part model gives three LOD scores)
plot(out, chr=c(1,5,6,13,15), lodcolumn=1:3,
     lty=1, col=c("black","red","blue"))

Estimate locations of crossovers

Description

Estimate the locations of crossovers for each individual on a given chromosome.

Usage

locateXO(cross, chr, full.info=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Chromosome to investigate (if unspecified, the first chromosome is considered). This should be a character string referring to a chromosome by name; numeric values are converted to strings.

full.info

If TRUE, output will include information on the left and right endpoints of the intervals to which recombination events are known, as well as the corresponding marker indices.

Details

For each individual we detemine the locations of obligate crossovers, and estimate their location to be at the midpoint between the nearest flanking typed markers.

The function currently only works for a backcross, intercross, or recombinant inbred line.

Value

A list with one component per individual. Each component is either NULL or is a numeric vector with the estimated crossover locations.

If full.info=TRUE, in place of a numeric vector with estimated locations, there is a matrix that includes those locations, the left and right endpoints of the intervals to which crossovers can be placed, the marker indices corresponding to those endpoint, and genotype codes for the genotypes to the left and right of each crossover. The final column indicates the number of typed markers between the current crossover and the next one (useful for identifying potential genotyping errors).

Author(s)

Karl W Broman, [email protected]

See Also

countXO, cleanGeno

Examples

data(hyper)
xoloc <- locateXO(hyper, chr=4)
table(sapply(xoloc, length))

Genetic locations of traits for the multitrait dataset

Description

A table with genetic locations of the traits in the multitrait dataset

Usage

data(locations)

Format

Each row is a trait with the following information: Name, Name of the trait (will be checked against the name in the cross object Chr, Chromosome of the trait cM, Location in cM from the start of the chromosome

Source

Additional information from the Arabidopsis RIL selfing experiment with Landsberg erecta (Ler) and Cape Verde Islands (Cvi) with 162 individuals scored (with errors at) 117 markers. Dataset obtained from GBIC - Groningen BioInformatics Centre

References

  • Keurentijes JJB, Fu J, de Vos CHR,Lommen A, Jansen RC et al (2006), The genetics of plant metabolism. Nature Genetics 38, 842–849.

  • Alonso-Blanco C., Peeters, A. J. and Koornneef, M. (2006) Development of an AFLP based linkage map of Ler, Col and Cvi Arabidopsis thaliana ecotypes and construction of a Ler/Cvi recombinant inbred line population. Plant J. 14(2), 259–271.

See Also

multitrait

Examples

## Not run: 
    data(multitrait)
    data(locations)
    multiloc <- addloctocross(multitrait,locations)
    results <- scanall(multiloc)
    mqmplot.cistrans(results,multiloc, 5, FALSE, TRUE)

## End(Not run)

LOD support interval

Description

Calculate a LOD support interval for a particular chromosome, using output from scanone.

Usage

lodint(results, chr, qtl.index, drop=1.5, lodcolumn=1, expandtomarkers=FALSE)

Arguments

results

Output from scanone, or a qtl object as output from refineqtl.

chr

A chromosome ID (if input results are from scanone (should have length 1).

qtl.index

Numeric index for a QTL (if input results are from refineqtl (should have length 1).

drop

LOD units to drop to form the interval.

lodcolumn

An integer indicating which of the LOD score columns should be considered (if input results are from scanone).

expandtomarkers

If TRUE, the interval is expanded to the nearest flanking markers.

Value

An object of class scanone indicating the estimated QTL position and the approximate endpoints for the LOD support interval.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, bayesint

Examples

data(hyper)

hyper <- calc.genoprob(hyper, step=0.5)
out <- scanone(hyper, method="hk")
lodint(out, chr=1)
lodint(out, chr=4)
lodint(out, chr=4, drop=2)
lodint(out, chr=4, expandtomarkers=TRUE)

Make a qtl object

Description

This function takes a cross object and specified chromosome numbers and positions and pulls out the genotype probabilities or imputed genotypes at the nearest pseudomarkers, for later use by the function fitqtl.

Usage

makeqtl(cross, chr, pos, qtl.name, what=c("draws","prob"))

Arguments

cross

An object of class cross. See read.cross for details.

chr

Vector indicating the chromosome for each QTL. (These should be character strings referring to the chromosomes by name.)

pos

Vector (of same length as chr) indicating the positions on the chromosome to be taken. If there is no marker or pseudomarker at a position, the nearest position is used.

qtl.name

Optional user-specified name for each QTL, used in the drop-one-term ANOVA table in fitqtl. If unspecified, the names will be of the form "Chr1@10" for a QTL on Chromsome 1 at 10 cM.

what

Indicates whether to pull out the imputed genotypes or the genotype probabilities.

Details

This function will take out the genotype probabilities and imputed genotypes if they are present in the input cross object. If both fields are missing in the input object, the function will report an error. Before running this function, the user must have first run either sim.geno (for what="draws") or calc.genoprob (for what="prob").

Value

An object of class qtl with the following elements (though only one of geno and prob will be included, according to whether what is given as "draws" or "prob"):

geno

Imputed genotypes.

prob

Genotype probabilities.

name

User-defined name for each QTL, or a name of the form "Chr1@10".

altname

QTL names of the form "Q1", "Q2", etc.

chr

Input vector of chromosome numbers.

pos

Input vector of chromosome positions.

n.qtl

Number of QTLs.

n.ind

Number of individuals.

n.gen

A vector indicating the number of genotypes for each QTL.

Author(s)

Hao Wu; Karl W Broman, [email protected]

See Also

fitqtl, calc.genoprob, sim.geno, dropfromqtl, replaceqtl, addtoqtl, summary.qtl, reorderqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c("1", "6", "13")
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- sim.geno(fake.f2, n.draws=8, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="draws")
summary(qtl)

An example genetic map

Description

A genetic map corresponding approximately to the mouse genome with a 10 cM marker spacing.

Usage

data(map10)

Format

An object of class map: a list whose components are vectors of marker locations. This map approximates the mouse genome, with 20 chromosomes (including the X chromosome) and 187 markers at an approximately 10 cM spacing. The markers are equally spaced on each chromosome, but the spacings are a bit above or below 10 cM, so that the lengths match those in the Mouse Genome Database.

See Also

sim.map, plotMap, pull.map

Examples

data(map10)
  plot(map10)

  mycross <- sim.cross(map10, type="f2", n.ind=100)

Convert genetic map from list to table.

Description

Convert a map object (as a list) to a table (as a data frame).

Usage

map2table(map, chr)

Arguments

map

A map object: a list whose components (corresponding to chromosomes) are either vectors of marker positions or matrices with two rows of sex-specific marker positions.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

Value

A data frame with two or three columns: chromosome and sex-averaged position, or chromosome, female position, and male position.

The row names are the marker names.

Author(s)

Karl W Broman, [email protected]

See Also

table2map, pull.map, est.map

Examples

data(fake.f2)
map <- pull.map(fake.f2)
map_as_tab <- map2table(map)

Simulated data for illustrating genetic map construction

Description

Simulated data for an F2 intercross, obtained using sim.cross, useful for illustrating the process of constructing a genetic map.

Usage

data(mapthis)

Format

An object of class cross. See read.cross for details.

Details

These are simulated data, consisting of 300 F2 individuals typed at 100 markers on five chromosomes. There are no real phenotypes, just a set of individual identifiers. The data were simulated for the purpose of illustrating the process of constructing a genetic map. The markers are all assigned to a single chromosome and in a random order, and there are a number of problematic markers and individuals.

See https://rqtl.org/tutorials/geneticmaps.pdf for a tutorial on how to construct a genetic map with these data.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W. (2010) Genetic map construction with R/qtl. Technical report #214, Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison

See Also

fake.f2, est.rf, est.map, formLinkageGroups, orderMarkers

Examples

data(mapthis)
summary(mapthis)
plot(mapthis)

General likelihood ratio test for association between marker pairs

Description

Calculate a LOD score for a general likelihood ratio test for each pair of markers, to assess their association.

Usage

markerlrt(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Value

The input cross object is returned with a component, rf, added. This is a matrix of size (tot.mar x tot.mar). The diagonal contains the number of typed meioses per marker, the upper and lower triangles each contain the LOD scores.

Author(s)

Karl W Broman, [email protected]

See Also

plotRF, est.rf, badorder

Examples

data(badorder)
badorder <- markerlrt(badorder)
plotRF(badorder)

Pull out the marker names from a cross

Description

Pull out the marker names from a cross object as one big vector.

Usage

markernames(cross, chr)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

Value

A vector of character strings (the marker names).

Author(s)

Karl W Broman, [email protected]

See Also

pull.map, phenames, chrnames

Examples

data(listeria)
markernames(listeria, chr=5)

Maximum peak in genome scan

Description

Print the row of the output from scanone that corresponds to the maximum LOD, genome-wide.

Usage

## S3 method for class 'scanone'
max(object, chr, lodcolumn=1, na.rm=TRUE, ...)

Arguments

object

An object of the form output by the function scanone: a data.frame whose third column is the LOD score.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

lodcolumn

An integer, indicating which of the LOD score columns should be considered in pulling out the peak (these are indexed 1, 2, ...).

na.rm

A logical indicating whether missing values should be removed.

...

Ignored.

Value

An object of class summary.scanone, to be printed by print.summary.scanone. This is a data.frame with one row, corresponding to the maximum LOD peak either genome-wide or for the particular chromosome specified.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, plot.scanone, summary.scanone

Examples

data(listeria)

listeria <- calc.genoprob(listeria, step=2.5)
out <- scanone(listeria, model="2part", upper=TRUE)
# Maximum peak for LOD(p,mu)
max(out)

# Maximum peak for LOD(p,mu) on chr 5
max(out,chr=5)

# Maximum peak for LOD(p,mu) on chromosomes other than chr 13
max(out,chr="-13")

# Maximum peak for LOD(p)
max(out, lodcolumn=2)

# Maximum peak for LOD(mu)
max(out, lodcolumn=3)

Maximum peak in genome scan to map a QTL to a phylogenetic tree

Description

Print the chromosome with the maximum LOD score across partitions, from the results of scanPhyloQTL.

Usage

## S3 method for class 'scanPhyloQTL'
max(object, chr, format=c("postprob", "lod"),
        ...)

Arguments

object

An object output by the function scanPhyloQTL.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

format

Indicates whether to provide LOD scores or approximate posterior probabilities; see the help file for summary.scanPhyloQTL.

...

Ignored at this point.

Details

The output, and the use of the argument format, is as in summary.scanPhyloQTL.

Value

An object of class summary.scanPhyloQTL, to be printed by print.summary.scanPhyloQTL.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Kim, S., An\'e, C. and Payseur, B. A. Mapping quantitative trait loci to a phylogenetic tree. In preparation.

See Also

scanPhyloQTL, plot.scanPhyloQTL, summary.scanPhyloQTL, max.scanone, inferredpartitions, simPhyloQTL

Examples

## Not run: 
# example map; drop X chromosome
data(map10)
map10 <- map10[1:19]

# simulate data
x <- simPhyloQTL(4, partition="AB|CD", crosses=c("AB", "AC", "AD"),
                 map=map10, n.ind=150,
                 model=c(1, 50, 0.5, 0))

# run calc.genoprob on each cross
x <- lapply(x, calc.genoprob, step=2)

# scan genome, at each position trying all possible partitions
out <- scanPhyloQTL(x, method="hk")

# maximum peak
max(out, format="lod")

# approximate posterior probabilities at peak
max(out, format="postprob")

# all peaks above a threshold for LOD(best) - LOD(2nd best)
summary(out, threshold=1, format="lod")

# all peaks above a threshold for LOD(best), showing approx post'r prob
summary(out, format="postprob", threshold=3)

# plot of results
plot(out)

## End(Not run)

Maximum peak in two-dimensional genome scan

Description

Print the pair of loci with the largest LOD score in the results of scantwo.

Usage

## S3 method for class 'scantwo'
max(object, lodcolumn=1,
    what=c("best", "full", "add", "int"),
    na.rm=TRUE, ...)

Arguments

object

An object of class scantwo, the output of the function scantwo.

lodcolumn

If the scantwo results contain LOD scores for multiple phenotypes, this argument indicates which to use.

what

Indicates for which LOD score the maximum should be reported.

na.rm

Ignored.

...

Ignored.

Details

This is very similar to the summary.scantwo function, though this pulls out one pair of positions.

If what="best", we find the pair of positions at which the LOD score for the full model (2 QTL + interaction) is maximized, and then also print the positions on that same pair of chromosomes at which the additive LOD score is maximized.

In the other cases, we pull out the pair of positions with the largest LOD score; which LOD score is considered is indicated by the what argument.

Value

An object of class summary.scantwo, to be printed by print.summary.scantwo, with the pair of positions with the maximum LOD score. (Which LOD score is considered is indicated by the what argument.)

Output of addpair

Note that, for output from addpair in which the new loci are indicated explicitly in the formula, the summary provided by max.scantwo is somewhat special.

All arguments (except, of course, the input object) are ignored.

If the formula is symmetric in the two new QTL, the output has just two LOD score columns: lod.2v0 comparing the full model to the model with neither of the new QTL, and lod.2v1 comparing the full model to the model with just one new QTL.

If the formula is not symmetric in the two new QTL, the output has three LOD score columns: lod.2v0 comparing the full model to the model with neither of the new QTL, lod.2v1b comparing the full model to the model in which the first of the new QTL is omitted, and lod.2v1a comparing the full model to the model with the second of the new QTL omitted.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, plot.scantwo, summary.scantwo

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=10)
out.2dim <- scantwo(fake.f2, method="hk")
max(out.2dim)

Move a marker to a new chromosome

Description

Move a specified marker to a different chromosome.

Usage

movemarker(cross, marker, newchr, newpos)

Arguments

cross

An object of class cross. See read.cross for details.

marker

The name of the marker to be moved (a character string).

newchr

The chromosome to which the marker should be moved.

newpos

The position (in cM) at which the marker should be placed. If missing, the marker is placed at the end of the chromosome.

Value

The input cross object, but with the specified marker moved to the specified chromosome.

All intermediate calculations (such as the results of calc.genoprob and est.rf) are removed.

Author(s)

Karl W Broman, [email protected]

See Also

switch.order

Examples

data(badorder)
badorder <- movemarker(badorder, "D2M937", 3, 48.15)
badorder <- movemarker(badorder, "D3M160", 2, 28.83)

Introduction to Multiple QTL Model (MQM) mapping

Description

Overview of the MQM mapping functions

Introduction

Multiple QTL Mapping (MQM) provides a sensitive approach for mapping quantititive trait loci (QTL) in experimental populations. MQM adds higher statistical power compared to many other methods. The theoretical framework of MQM was introduced and explored by Ritsert Jansen, explained in the ‘Handbook of Statistical Genetics’ (see references), and used effectively in practical research, with the commercial ‘mapqtl’ software package. Here we present the first free and open source implementation of MQM, with extra features like high performance parallelization on multi-CPU computers, new plots and significance testing.

MQM is an automatic three-stage procedure in which, in the first stage, missing data is ‘augmented’. In other words, rather than guessing one likely genotype, multiple genotypes are modeled with their estimated probabilities. In the second stage important markers are selected by multiple regression and backward elimination. In the third stage a QTL is moved along the chromosomes using these pre-selected markers as cofactors, except for the markers in the window around the interval under study. QTL are (interval) mapped using the most ‘informative’ model through maximum likelihood. A refined and automated procedure for cases with large numbers of marker cofactors is included. The method internally controls false discovery rates (FDR) and lets users test different QTL models by elimination of non-significant cofactors.

R/qtl-MQM has the following advantages:

  • Higher power to detect linked as well as unlinked QTL, as long as the QTL explain a reasonable amount of variation

  • Protection against overfitting, because it fixes the residual variance from the full model. For this reason more parameters (cofactors) can be used compared to, for example, CIM

  • Prevention of ghost QTL (between two QTL in coupling phase)

  • Detection of negating QTL (QTL in repulsion phase)

Note

The current implementation of R/qtl-MQM has the following limitations: (1) MQM is limited to experimental crosses F2, BC, and selfed RIL, (2) MQM does not treat sex chromosomes differently from autosomal chromosomes - though one can introduce sex as a cofactor. Future versions of R/qtl-MQM may improve on these points. Check the website and change log (https://github.com/kbroman/qtl/blob/main/NEWS.md) for updates.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

References

  • Arends D, Prins P, Jansen RC. R/qtl: High-throughput multiple QTL mapping. Bioinformatics, to appear

  • Jansen RC, (2007) Quantitative trait loci in inbred lines. Chapter 18 of Handbook of Stat. Genetics 3rd edition. John Wiley & Sons, Ltd.

  • Jansen RC, Nap JP (2001), Genetical genomics: the added value from segregation. Trends in Genetics, 17, 388–391.

  • Jansen RC, Stam P (1994), High resolution of quantitative traits into multiple loci via interval mapping. Genetics, 136, 1447–1455.

  • Jansen RC (1993), Interval mapping of multiple quantitative trait loci. Genetics, 135, 205–211.

  • Swertz MA, Jansen RC. (2007), Beyond standardization: dynamic software infrastructures for systems biology. Nat Rev Genet. 3, 235–243.

  • Dempster, A. P., Laird, N. M. and Rubin, D. B. (1977) Maximum likelihood from incomplete data via the EM algorithm. J. Roy. Statist. Soc. B, 39, 1–38.

See Also

Examples

data(map10)                    # Genetic map modeled after mouse

# simulate a cross (autosomes 1-10)
qtl <- c(3,15,1,0)             # QTL model: chr, pos'n, add've & dom effects
cross <- sim.cross(map10[1:10],qtl,n=100,missing.prob=0.01)

# MQM
crossaug <- mqmaugment(cross)  # Augmentation
cat(crossaug$mqm$Nind,'real individuals retained in dataset',
    crossaug$mqm$Naug,'individuals augmented\n')

result <- mqmscan(crossaug)    # Scan

# show LOD interval of the QTL on chr 3
lodint(result,chr=3)

MQM augmentation

Description

Fill in missing genotypes for MQM mapping. For each missing or incomplete marker it fills in (or ‘augments’) all possible genotypes, thus creating new candidate ‘individuals’. The probability of each indidual is calculated using information on neighbouring markers and recombination frequencies. When a genotype of an augmented genotype is less likely than the minprob parameter it is dropped from the dataset. The augmented list of individuals is returned in a new cross object. For a full discussion on augmentation see the MQM tutorial online.

Usage

mqmaugment(cross, maxaugind=82, minprob=0.1,
           strategy=c("default","impute","drop"),
           verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

maxaugind

Maximum number of augmentations per individual. The default of 82 allows for six missing markers for an individual in a BC cross (26=642^6=64) and four missing markers in an F2 (34=813^4=81). When a large number of markers are missing this default number is quickly reached.

minprob

Return individuals with augmented genotypes that have at least this probability of occurring. minprob is a value between 0 and 1. For example a value of 0.5 will drop all genotypes that are half as likely as the most likely genotype (candidate of the individual). The default value of 0.1 will drop all genotypes that are less likely of ocurring than 1 in 10, compared against the most likely genotype. Use a value of 1.0 to return a single filled in genotype for each individual.

strategy

When individuals have too much missing data and augmentation fails three options are provided: 1. "default": Calculate genotypes at missing marker positions, accounting for minprob, and add this individual to the set. 2. "impute": Calculate the most likely genotypes at missing marker positions and impute maxaugind individual-variants around the most likely genotype. 3. "drop": Drop individuals that cannot be augmented from the dataset, this option is not advised because information from the dropped individuals will be lost.

verbose

If TRUE, give verbose output

Value

Returns the cross object with augmented individuals (many individuals from the data set will be repeated multiple times). Some individuals may have been dropped completely when the probability falls below minprob. An added component to the cross object named mqm contains information on exactly which individuals are retained and repeated.

Note

The sex chromosome 'X' is treated like autosomes during augmentation. With an F2 the sex chromosome is not considered. This will change in a future version of MQM. Run with verbose=TRUE to verify how many individuals are augmented versus moved to the second augmentation round. This could have an effect on the resulting dataset or check the return cross$mqm values. Compare results by using minprob=1.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

data(map10)                    # Genetic map modeled after mouse

# simulate a cross (autosomes 1-10)
qtl <- c(3,15,1,0)             # QTL model: chr, pos'n, add've & dom effects
cross <- sim.cross(map10[1:10],qtl,n=100,missing.prob=0.01)

# MQM
crossaug <- mqmaugment(cross)  # Augmentation
cat(crossaug$mqm$Nind,'real individuals retained in dataset',
    crossaug$mqm$Naug,'individuals augmented\n')

result <- mqmscan(crossaug)    # Scan

# show LOD interval of the QTL on chr 3
lodint(result,chr=3)

Automatic setting of cofactors, taking marker density into account

Description

Sets cofactors, taking underlying marker density into account. Together with mqmscan cofactors are selected through backward elimination.

Usage

mqmautocofactors(cross, num=50, distance=5, dominance=FALSE, plot=FALSE, verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

num

Number of cofactors to set (warns when setting too many cofactors).

distance

Minimal distance between two cofactors, in cM.

dominance

If TRUE, create a cofactor list that is safe to use with the dominance scan mode of MQM. See mqmscan for details.

plot

If TRUE, plots a genetic map displaying the selected markers as cofactors.

verbose

If TRUE, give verbose output.

Value

A list of cofactors to be used with mqmscan.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

data(hyper)                     # hyper dataset
    
    hyperfilled <- fill.geno(hyper)
    cofactors <- mqmautocofactors(hyperfilled,15)	# Set 15 Cofactors
    result <- mqmscan(hyperfilled,cofactors)	# Backward model selection
    mqmgetmodel(result)

MQM marker extraction

Description

Extract the real markers from a cross object that includes pseudo markers

Usage

mqmextractmarkers(mqmresult)

Arguments

mqmresult

result from mqmscan, including pseudo markers

Value

Returns a scanone object with the pseudo markers removed

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

data(multitrait)

multitrait <- fill.geno(multitrait)

result <- mqmscan(multitrait)
newresult <- mqmextractmarkers(result)

Fetch significant markers after permutation analysis

Description

Fetch significant makers after permutation analysis. These markers can be used as cofactors for model selection in a forward stepwise approach.

Usage

mqmfind.marker(cross, mqmscan = NULL, perm = NULL, alpha = 0.05, verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

mqmscan

Results from either scanone or mqmscan

perm

a scanoneperm object

alpha

Threshold value, everything with significance < alpha is reported

verbose

Display more output on verbose=TRUE

Value

returns a matrix with at each row a significant marker (determined from the scanoneperm object) and with columns: markername, chr and pos (cM)

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

# Use the multitrait dataset
data(multitrait)

# Set cofactors at each 3th marker
cof <- mqmsetcofactors(multitrait,3)

# impute missing genotypes
multitrait <- fill.geno(multitrait)

# log transform the 7th phenotype
multitrait <- transformPheno(multitrait, 7)

# Bootstrap 50 runs in batches of 10
## Not run: result <- mqmpermutation(multitrait,scanfunction=mqmscan,cofactors=cof,
                         pheno.col=7,n.perm=50,batchsize=10)

## End(Not run)

# Create a permutation object
f2perm <- mqmprocesspermutation(result)

# What LOD score is considered significant ?
summary(f2perm)

# Find markers with a significant QTL effect (First run is original phenotype data)
marker <- mqmfind.marker(multitrait,result[[1]],f2perm)

# Print it to the screen
marker

Retrieve the QTL model used in mapping from the results of an MQM scan

Description

Retrieves the QTL model used for scanning from the output of an MQM scan. The model only contains the selected cofactors significant at the specified cofactor.significance from the results of an mqm scan

Usage

mqmgetmodel(scanresult)

Arguments

scanresult

An object returned by mqmscan, including cofactors and QTL model.

Value

The function returns the multiple QTL model created, which consists of the cofactors selected during the modeling phase of the algorithm. This model was used when scanning for additional QTL in the mqmscan function. The format of the model is compatible with the makeqtl function. For more information about the format of the model see the makeqtl page. When no cofactor was selected in the modeling phase no model was created, then this function will return a NULL value.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

data(hyper)
        
    hyperfilled <- fill.geno(hyper)
    cofactors <- mqmsetcofactors(hyperfilled,4)
    result <- mqmscan(hyperfilled,cofactors)
    mqmgetmodel(result)
    plot(mqmgetmodel(result))

Estimate QTL LOD score significance using permutations or simulations

Description

Two randomization approaches to obtain estimates of QTL significance:

  • Random redistribution of traits (method='permutation')

  • Random redistribution of simulated trait values (method='simulation')

Calculations can be parallelized using the SNOW package.

Usage

mqmpermutation(cross, scanfunction=scanone, pheno.col=1, multicore=TRUE,
               n.perm=10, file="MQM_output.txt",
               n.cluster=1, method=c("permutation","simulation"),
               cofactors=NULL, plot=FALSE, verbose=FALSE, ...)

Arguments

cross

An object of class cross. See read.cross for details.

scanfunction

Function to use when mappingQTL's (either scanone,cim or mqm)

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This can be a vector of integers.

multicore

Use multicore (if available)

n.perm

Number of permutations to perform (DEFAULT=10, should be 1000, or higher, for publications)

file

Name of the intermediate output file used

n.cluster

Number of child processes to split the job into

method

What kind permutation should occur: permutation or simulation

cofactors

cofactors, only used when scanfunction is mqm. List of cofactors to be analysed in the QTL model. To set cofactors use mqmautocofactors or mqmsetcofactors

.

plot

If TRUE, make a plot

verbose

If TRUE, print tracing information

...

Parameters passed through to the scanone, cim or mqmscan functions

Details

Analysis of scanone, cim or mqmscan to scan for QTL in shuffled/randomized data. It is recommended to also install the snow library. The snow library allows calculations to run on multiple cores or even scale it up to an entire cluster, thus speeding up calculation.

Value

Returns a mqmmulti object. this object is a list of scanone objects that can be plotted using plot.scanone(result[[trait]])

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

References

  • Bruno M. Tesson, Ritsert C. Jansen (2009) Chapter 3.7. Determining the significance threshold eQTL Analysis in Mice and Rats 1, 20–25

  • Churchill, G. A. and Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

  • Rossini, A., Tierney, L., and Li, N. (2003), Simple parallel statistical computing. R. UW Biostatistics working paper series University of Washington. 193

  • Tierney, L., Rossini, A., Li, N., and Sevcikova, H. (2004), The snow Package: Simple Network of Workstations. Version 0.2-1.

See Also

Examples

# Use the multitrait dataset
data(multitrait)



multitrait <- calc.genoprob(multitrait)
result <- mqmpermutation(multitrait,pheno.col=7, n.perm=2, batchsize=2)

## Not run: #Set 50 cofactors
cof <- mqmautocofactors(multitrait,50)

## End(Not run)

multitrait <- fill.geno(multitrait)
result <- mqmpermutation(multitrait,scanfunction=mqmscan,cofactors=cof,
                         pheno.col=7, n.perm=2,batchsize=2,verbose=FALSE)

#Create a permutation object
f2perm <- mqmprocesspermutation(result)

#Get Significant LOD thresholds
summary(f2perm)

Circular genome plot for MQM

Description

Circular genome plot - shows QTL locations and relations.

Usage

mqmplot.circle(cross,result,highlight=0,spacing=25, interactstrength=2,
               axis.legend=TRUE, col.legend=FALSE, verbose=FALSE, transparency=FALSE)

Arguments

cross

An object of class cross with optionally phenotype locations. See read.cross for details on reading in cross objects, and optionally addloctocross for adding phenotype locations.

result

An object of class mqmmulti or scanone. See mqmscanall scanone for details.

highlight

With a mqmmulti object, highlight this phenotype (value between one and the number of results in the mqmmultiobject)

interactstrength

When highlighting a trait, consider interactions significant they have a change of more than interactstrength*SEs. A higher value will show less interactions. However the interactions reported at higher interactstrength values will generaty be more reliable.

spacing

User defined spacing between chromosomes in cM

axis.legend

When set to FALSE, suppresses the legends. (defaults to plotting legends besides the axis.

col.legend

With a mqmmulti object, plots a legend for the non-highlighed version

transparency

Use transparency when drawing the plots (defaults to no transparency)

verbose

Be verbose

Details

Depending on the input of the result being either scanone or mqmmulti a different plot is drawn. If model information is present from mqmscan (by setting cofactors) This will be highlighted in red (see example). If phenotypes have genetic locations (e.g. eQTL) they will be plotted on the genome otherwise phenotypes will be plotted in the middle of the circle (with a small offset) Locations can be added by using the addloctocross function.

Value

Plotting routine, no return

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

data(locations)


multifilled <- fill.geno(multitrait)                    # impute missing genotypes
multicof <- mqmsetcofactors(multitrait,10)              # create cofactors
multiloc <- addloctocross(multifilled,locations)        # add phenotype information to cross
multires <- mqmscanall(multifilled,cofactors=multicof)  # run mqmscan for all phenotypes

#Basic mqmmulti, color = trait, round circle = significant
mqmplot.circle(multifilled,multires)

#mqmmulti with locations of traits in multiloc
mqmplot.circle(multiloc,multires)

#mqmmulti with highlighting
mqmplot.circle(multitrait,multires,highlight=3)

#mqmmulti with locations of traits in multiloc and highlighting
mqmplot.circle(multiloc,multires,highlight=3)

cis-trans plot

Description

Plot results for a genomescan using a multiple-QTL model. With genetic location for the traits it is possible to show cis- and trans- locations, and detect trans-bands

Usage

mqmplot.cistrans(result, cross, threshold=5, onlyPEAK=TRUE,
                 highPEAK=FALSE, cisarea=10, pch=22, cex=0.5,
                 verbose=FALSE, ...)

Arguments

result

An object of class mqmmulti. See mqmscanall for details.

cross

An object of class cross. See read.cross for details.

threshold

Threshold value in LOD, Markers that have a LOD score above this threshold are plotted as small squares (see pch parameter). The markers with LODscores below this threshold are not visible

onlyPEAK

Plot only the peak markers ? (TRUE/FALSE) (Peak markers are markers that have a QTL likelihood above threshold and higher than other markers in the same region)

highPEAK

Highlight peak markers ? (TRUE/FALSE). When using this option peak markers (the marker with the highest LOD score in a region above the threshold gets an 25% increase in size and is displayed in red)

cisarea

Adjust the two green lines around the line y=x

pch

What kind of character is used in plotting of the figure (Default: 22, small square)

cex

Size of the points plotted (default to 0.5 half of the original size)

verbose

If TRUE, give verbose output

...

Extra parameters will be passed to points

Value

Plotting routine, so no return

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

data(locations)
multiloc <- addloctocross(multitrait,locations)
multiloc <- calc.genoprob(multiloc)
results <- scanall(multiloc, method="hk")
mqmplot.cistrans(results, multiloc, 5, FALSE, TRUE)

Plot clustered heatmap of MQM scan on multiple phenotypes

Description

Plot the results from a MQM scan on multiple phenotypes.

Usage

mqmplot.clusteredheatmap(cross, mqmresult, directed=TRUE, legend=FALSE,
                         Colv=NA, scale="none", verbose=FALSE,
                         breaks = c(-100,-10,-3,0,3,10,100),
                         col = c("darkblue","blue","lightblue","yellow",
                                 "orange","red"), ...)

Arguments

cross

An object of class cross. See read.cross for details.

mqmresult

Result object from mqmscanall, the object needs to be of class mqmmulti

directed

Take direction of QTLs into account (takes more time because of QTL direction calculations

legend

If TRUE, add a legend to the plot

Colv

Cluster only the Rows, the columns (Markers) should not be clustered

scale

character indicating if the values should be centered and scaled in either the row direction or the column direction, or none. The default "none"

verbose

If TRUE, give verbose output.

breaks

Color break points for the LOD scores

col

Colors used between breaks

...

Additional arguments passed to heatmap.

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

multitrait <- fill.geno(multitrait) # impute missing genotype data
result <- mqmscanall(multitrait, logtransform=TRUE)
cresults <- mqmplot.clusteredheatmap(multitrait,result)
groupclusteredheatmap(multitrait,cresults,10)

Plot cofactors on the genetic map

Description

Plots cofactors as created by mqmsetcofactors or mqmautocofactors on the genetic map.

Usage

mqmplot.cofactors(cross,cofactors, ...)

Arguments

cross

An object of class cross. See read.cross for details.

cofactors

List of cofactors to be analysed in the QTL model. To set cofactors use mqmautocofactors or mqmsetcofactors

.

...

Passed to plot.qtl

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)
cof1 <- mqmsetcofactors(multitrait,20)
cof2 <- mqmsetcofactors(multitrait,10)
op <- par(mfrow=c(2,1))
mqmplot.cofactors(multitrait,cof1,col="blue")
mqmplot.cofactors(multitrait,cof2,col="blue")
op <- par(mfrow=c(1,1))

Plot LOD*Effect curves of a multiple-QTL model

Description

Plot the LOD*Effect curve for a genome scan with a multiple-QTL model (the output of mqmscan).

Usage

mqmplot.directedqtl(cross, mqmresult, pheno.col=1, draw = TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

mqmresult

Results from mqmscan of type scanone

pheno.col

From which phenotype in the crossobject are the result calculated

draw

If TRUE, draw the figure.

Value

Returns a scanone object, with added the effectsign calculated internally by the function effect.scan. For more info on the scanone object see: scanone

Author(s)

Danny Arends [email protected]

See Also

Examples

#Simulated F2 Population
f2qtl <- c(3,15,1,0)                                    # QTL at chromosome 3
data(map10)                                             # Mouse genetic map

f2cross <- sim.cross(map10,f2qtl,n=100,type="f2")       # Simulate a F2 Cross
f2cross <- fill.geno(f2cross)                           # Fill in missing genotypes
f2result <- mqmscan(f2cross)                        # Do a MQM scan of the genome
mqmplot.directedqtl(f2cross,f2result)

Heatmap of a genome of MQM scan on multiple phenotypes

Description

Plotting routine to display a heatmap of results obtained from a multiple-QTL model on multiple phenotypes (the output of mqmscanall)

Usage

mqmplot.heatmap(cross, result, directed=TRUE, legend=FALSE, breaks =
c(-100,-10,-3,0,3,10,100), col =
c("darkblue","blue","lightblue","yellow","orange","red"), ...)

Arguments

cross

An object of class cross. See read.cross for details.

result

Result object from mqmscanall, the object needs to be of class mqmmulti

directed

Take direction of QTLs into account (takes more time because of QTL direction calculations

legend

If TRUE, add a legend to the plot

breaks

Color break points for the LOD scores

col

Colors used between breaks

...

Additional arguments passed to the image function

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

multitrait <- fill.geno(multitrait) # impute missing genotype data
result <- mqmscanall(multitrait, logtransform=TRUE)
mqmplot.heatmap(multitrait,result)

Plot the results from a genomescan using a multiple-QTL model on multiple phenotypes

Description

Plotting routine to display the results from a multiple-QTL model on multiple phenotypes. It supports four different visualizations: a contourmap, heatmap, 3D graph or a multiple QTL plot created by using plot.scanone on the mqmmulti object

Usage

mqmplot.multitrait(result, type=c("lines","image","contour","3Dplot"),
                   group=NULL, meanprofile=c("none","mean","median"),
                   theta=30, phi=15, ...)

Arguments

result

Result object from mqmscanall

type

Selection of the plot method to visualize the data: "lines" (defaut plotting option), "image", "contour" and "3Dplot"

group

A numeric vector indicating which traits to plot. NULL means no grouping

meanprofile

Plot a mean/median profile from the group selected

theta

Horizontal axis rotation in a 3D plot

phi

Vertical axis rotation in a 3D plot

...

Additional arguments passed to plot.

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

multitrait <- fill.geno(multitrait) # impute missing genotype data
result <- mqmscanall(multitrait, logtransform=TRUE)
mqmplot.multitrait(result,"lines")
mqmplot.multitrait(result,"contour")
mqmplot.multitrait(result,"image")
mqmplot.multitrait(result,"3Dplot")

Plot results from mqmpermutation

Description

Plotting routine to display the results from a permutation QTL scan. (the output of mqmpermutation)

Usage

mqmplot.permutations(permutationresult, ...)

Arguments

permutationresult

mqmmulti object returned by mqmpermutation permutation analysis.

...

Extra arguments passed to polyplot

Value

No value returned (plotting routine)

Author(s)

Danny Arends [email protected] , Rutger Brouwer

See Also

Examples

# Simulated F2 Population
# QTL at chromosome 3
f2qtl <- c(3,15,1,0)

# Mouse genetic map
data(map10)


# Simulate a F2 Cross
f2cross <- sim.cross(map10,f2qtl,n=100,type="f2")
f2cross <- calc.genoprob(f2cross)
## Not run: # Permutations to obtain significance threshold
f2result <- mqmpermutation(f2cross, n.perm=1000, method="permutation")

## End(Not run)

# Plot results
mqmplot.permutations(f2result)

Plot LOD curves of a multiple-QTL model

Description

Plot the LOD curve for a genome scan for a single trait, with a multiple-QTL model (the output of mqmscan).

Usage

mqmplot.singletrait(result, extended = 0 ,...)

Arguments

result

mqmscan result.

extended

Extended plotting of the information content

...

Extra arguments passed to plot.scanone

Author(s)

Danny Arends [email protected]

See Also

Examples

#Simulated F2 Population
f2qtl <- c(3,15,1,0)                                    # QTL at chromosome 3
data(map10)                                             # Mouse genetic map

f2cross <- sim.cross(map10,f2qtl,n=100,type="f2")       # Simulate a F2 Cross
f2cross <- mqmaugment(f2cross)
f2result <- mqmscan(f2cross)                        # Do a MQM scan of the genome
mqmplot.singletrait(f2result)					# Use our fancy plotting routine

Convert mqmmulti objects into a scanoneperm object

Description

Function to convert mqmmulti objects into a scanoneperm object, this allows the use of R/qtl methods for permutation analysis that do not support the output of a multiple QTL scan using mqm's outputstructure.

Usage

mqmprocesspermutation(mqmpermutationresult = NULL)

Arguments

mqmpermutationresult

mqmmulti object obtained after performing permutations on a single trait.using the function mqmpermutation

Value

Output of the algorithm is a scanoneperm object. See also: summary.scanoneperm

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

# QTL at chromosome 3
f2qtl <- c(3,15,1,0)

# Mouse genetic map
data(map10)


# Simulate a F2 Cross
f2cross <- sim.cross(map10,f2qtl,n=100,type="f2")
## Not run: # Bootstrap MQM mapping on the f2cross
f2result <- mqmpermutation(f2cross,scanfunction=mqmscan)

## End(Not run)

# Create a permutation object
f2perm <- mqmprocesspermutation(f2result)

# What LOD score is considered significant?
summary(f2perm)

Genome scan with a multiple QTL model (MQM)

Description

Genome scan with a multiple QTL model.

Usage

mqmscan(cross, cofactors=NULL, pheno.col = 1,
  model=c("additive","dominance"), forceML=FALSE,
  cofactor.significance=0.02, em.iter=1000,
  window.size=25.0, step.size=5.0,
  logtransform = FALSE, estimate.map = FALSE,
  plot=FALSE, verbose=FALSE, outputmarkers=TRUE,
  multicore=TRUE, batchsize=10, n.clusters=1, test.normality=FALSE,off.end=0
  )

Arguments

cross

An object of class cross. See read.cross for details.

cofactors

List of cofactors to be analysed as cofactors in backward elimination procedure when building the QTL model. See mqmsetcofactors on how-to manually set cofactors for backward elimination. Or use mqmautocofactors for automatic selection of cofactors. Only three kind of (integer) values are allowed in the cofactor list. (0: no cofactor at this marker, 1: Use this marker as an additive cofactor, 2: Use this marker as an sexfactor (Dominant cofactor))

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This can be a vector of integers; One may also give a character strings matching the phenotype names. Finally, one may give a numeric vector of phenotypeIDs. This should consist of integers with 0 < value < no. phenotypes.

model

When scanning for QTLs should haplotype dominance be considered in an F2 intercross. Using the dominance model we scan for additive effects but also allow an additional effect where AA+AB versus BB and AA versus AB+BB. This setting is ignored for BC and RIL populations

forceML

Specify which statistical method to use to estimate variance components to use when QTL modeling and mapping. Default usage is the Restricted maximum likelihood approach (REML). With this option a user can disable REML and use maximum likelihood.

cofactor.significance

Significance level at which a cofactor is considered significant. This is estimated using an analysis of deviance, and compared to the level specified by the user. The cofactors that dont reach this level of statistical significance are NOT used in the mapping stage. Value between 0 and 1

em.iter

Maximum number of iterations for the EM algorithm to converge

window.size

Window size for mapping QTL locations, this parameter is used in the interval mapping stage. When calculating LOD scores at a genomic position all cofactors within window.size are dropped to estimate the (unbiased) effect of the location under interest.

step.size

Step size used in interval mapping. A lower step.size parameter increases the number of output points, this creates a smoother QTL profile

off.end

Distance (in cM) past the terminal markers on each chromosome to which the genotype simulations will be carried.

logtransform

Indicate if the algorithm should do a log transformation on the trait data in the pheno.col

estimate.map

Should Re-estimation of the marker locations on the genetic map occur before mapping QTLs. This method is deprecated rather use the est.map function in R/qtl. This is because no map is returned into the crossobject. The old map remains in the cross object.

plot

plot the results (default FALSE)

verbose

verbose output

outputmarkers

If TRUE (the default), the results include the marker locations as well as along a grid of pseudomarkers; if FALSE, the results include only the grid positions.

multicore

Use multicore (if available)

batchsize

Number of traits being analyzed as a batch.

n.clusters

Number of child processes to split the job into.

test.normality

If TRUE, test whether the phenotype follows a normal distribution via mqmtestnormal.

Value

When scanning a single phenotype the function returns a scanone object.

The object contains a matrix of three columns for LOD scores, information content and LOD*information content with pseudo markers sorted in increasing order. For more information on the scanone object see: scanone

Note

The resulting scanone object itself can be visualized using the standard R/qtl plotting routines (plot.scanone) or specialized function to show the mqm model (mqmplot.singletrait) and QTL profile. If cofactors were specified the QTL model used in scanning is also returned as a named attribute of the scanone object called mqmmodel. It can be extracted from the resulting scanone object by using the mqmgetmodel function or the attr function.

Also note the estimate.map parameter does not return its re-estimated genetic map, altough it is used internally. When scanning multiple genotypes a mqmmulti object is created. This object is just a list composed of scanone objects. The results for a single trait can be obtained from the mqmmulti object, in scanone format.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

data(map10)                    # Genetic map modeled after mouse

# simulate a cross (autosomes 1-10)
qtl <- c(3,15,1,0)             # QTL model: chr, pos'n, add've & dom effects
cross <- sim.cross(map10[1:10],qtl,n=100,missing.prob=0.01)

# MQM
crossaug <- mqmaugment(cross)  # Augmentation
cat(crossaug$mqm$Nind,'real individuals retained in dataset',
    crossaug$mqm$Naug,'individuals augmented\n')

result <- mqmscan(crossaug)    # Scan

# show LOD interval of the QTL on chr 3
lodint(result,chr=3)

Parallelized MQM on multiple phenotypes in a cross object

Description

Parallelized QTL analysis using MQM on multiple phenotypes in a cross object (uses SNOW)

Usage

mqmscanall(cross, multicore=TRUE, n.clusters = 1,batchsize=10,cofactors=NULL, ...)

Arguments

cross

An object of class cross. See read.cross for details.

multicore

Use multiple cores (only if the package SNOW is available, otherwise this setting will be ignored)

n.clusters

Number of parallel processes to spawn, recommended is setting this lower than the number of cores in the computer

batchsize

Batch size. The entire set is split in jobs to reduce memory load per core. Each job contains batchsize number of traits per job.

cofactors

cofactors, only used when scanfunction is mqmscan. List of cofactors to be analysed in the QTL model. To set cofactors use mqmautocofactors or mqmsetcofactors

.

...

Parameters passed through to the mqmscan function used in scanning for QTLs

Details

Uses mqmscan to scan for QTL's for each phenotype in the cross object. It is recomended that the package SNOW is installed before using this function on large numbers of phenotypes.

Value

Returns a MQMmulti object. This object is a list of scanone objects that can be plotted using plot.scanone(result[[trait]]) or using mqmplot.multitrait(result)

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

References

  • Rossini, A., Tierney, L., and Li, N. (2003), Simple parallel statistical computing. R. UW Biostatistics working paper series University of Washington. 193

  • Tierney, L., Rossini, A., Li, N., and Sevcikova, H. (2004), The snow Package: Simple Network of Workstations. Version 0.2-1.

See Also

Examples

#Doing a multitrait analysis
data(multitrait)

multitrait <- calc.genoprob(multitrait)
cof <- mqmsetcofactors(multitrait,3)
multitrait <- fill.geno(multitrait)
result <- mqmscanall(multitrait,cofactors=cof,batchsize=5)
mqmplot.multitrait(result,"lines")

Estimate FDR for multiple trait QTL analysis

Description

Estimate the false discovery rate (FDR) for multiple trait analysis

Usage

mqmscanfdr(cross, scanfunction=mqmscanall,
  thresholds=c(1,2,3,4,5,7,10,15,20), n.perm=10,
  verbose=FALSE, ...
  )

Arguments

cross

An object of class cross. See read.cross for details.

scanfunction

QTL mapping function, Note: Must use scanall or mqmscanall. Otherwise this will not produce usefull results. Reason: We need a function that maps all traits ecause of the correlation structure which is not changed (between traits) during permutation (Valis options: scanall or mqmscanall)

thresholds

False discovery rate (FDR) is calculated for peaks above these LOD thresholds (DEFAULT=Range from 1 to 20, using 10 thresholds) Parameter is a list of LOD scores at which FDR is calculated.

n.perm

Number of permutations (DEFAULT=10 for quick analysis, however for publications use 1000, or higher)

verbose

verbose output

...

Parameters passed to the mapping function

Details

This function wraps the analysis of scanone, cim and mqmscan to scan for QTL in shuffled/randomized data. It is recommended to also install the snow library for parallelization of calculations. The snow library allows calculations to run on multiple cores or even scale it up to an entire cluster, thus speeding up calculation by the number of computers used.

Value

Returns a data.frame with 3 columns: FalsePositives, FalseNegatives and False Discovery Rates. In the rows the userspecified thresholds are with scores for the 3 columns.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

References

  • Bruno M. Tesson, Ritsert C. Jansen (2009) Chapter 3.7. Determining the significance threshold eQTL Analysis in Mice and Rats 1, 20–25

  • Churchill, G. A. and Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

  • Rossini, A., Tierney, L., and Li, N. (2003), Simple parallel statistical computing. R. UW Biostatistics working paper series University of Washington. 193

  • Tierney, L., Rossini, A., Li, N., and Sevcikova, H. (2004), The snow Package: Simple Network of Workstations. Version 0.2-1.

See Also

Examples

data(multitrait)

# impute missing genotype data
multitrait <- fill.geno(multitrait)
## Not run: # Calculate the thresholds
result <- mqmscanfdr(multitrait, threshold=10.0, n.perm=1000)

## End(Not run)

Set cofactors at fixed intervals, to be used with MQM

Description

Set cofactors, at fixed marker intervals. Together with mqmscan cofactors are selected through backward elimination.

Usage

mqmsetcofactors(cross, each = NULL, cofactors=NULL, sexfactors=NULL, verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

each

Every 'each' marker will be used as a cofactor, when each is used the cofactors and sexfactors parameter is ignored

cofactors

List of cofactors to be analysed in the QTL model. To set cofactors use mqmautocofactors or mqmsetcofactors; when each is set, this parameter is ignored

sexfactors

list of markers which should be treated as dominant cofactors (sexfactors), when each is set, this parameter is ignored

verbose

If TRUE, print tracing information.

Value

An list of cofactors to be passed into mqmscan.

Author(s)

Ritsert C Jansen; Danny Arends; Pjotr Prins; Karl W Broman [email protected]

See Also

Examples

data(hyper)                                 # Hyper dataset
    
    hyperfilled <- fill.geno(hyper)
  # Automatic cofactors every third marker
    cofactors <- mqmsetcofactors(hyperfilled,3)
    result <- mqmscan(hyperfilled,cofactors)	# Backward model selection
    mqmgetmodel(result)
  #Manual cofactors at markers 3,6,9,12,40 and 60
  cofactors <- mqmsetcofactors(hyperfilled,cofactors=c(3,6,9,12,40,60))
    result <- mqmscan(hyperfilled,cofactors)	# Backward model selection
    mqmgetmodel(result)

Shapiro normality test used for MQM

Description

Wraps a shapiro's normality test from the nortest package. This function is used in MQM to test the normality of the trait under investigation

Usage

mqmtestnormal(cross, pheno.col = 1,significance=0.05, verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This can be a vector of integers.

significance

Significance level used in the normality test. Lower significance levels will accept larger deviations from normality.

verbose

If TRUE, print result as well as return it.

Details

For augmented data (as from mqmaugment), the cross is first reduced to distinct individuals. Furthermore the shapiro used to test normality works only for 3 <= nind(cross) <= 5000

Value

Boolean indicating normality of the trait in pheno.col. (FALSE when not normally distributed.)

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)

# test normality of 7th phenotype
mqmtestnormal(multitrait, pheno.col=7)

# take log
multitrait <- transformPheno(multitrait, pheno.col=7, transf=log)

# test again
mqmtestnormal(multitrait, pheno.col=7)

Example Cross object from R/QTL with multiple traits

Description

Cross object from R/QTL, an object of class cross from R/QTL. See read.cross for details.

Usage

data(multitrait)

Format

Cross object from R/QTL

Details

Arabidopsis recombinant inbred lines by selfing. There are 162 lines, 24 phenotypes, and 117 markers on 5 chromosomes.

Source

Part of the Arabidopsis RIL selfing experiment with Landsberg erecta (Ler) and Cape Verde Islands (Cvi) with 162 individuals scored (with errors at) 117 markers. Dataset obtained from GBIC - Groningen BioInformatics Centre

References

  • Keurentjes, J. J. and Fu, J. and de Vos, C. H. and Lommen, A. and Hall, R. D. and Bino, R. J. and van der Plas, L. H. and Jansen, R. C. and Vreugdenhil, D. and Koornneef, M. (2006), The genetics of plant metabolism. Nature Genetics. 38-7, 842–849.

  • Alonso-Blanco, C. and Peeters, A. J. and Koornneef, M. and Lister, C. and Dean, C. and van den Bosch, N. and Pot, J. and Kuiper, M. T. (1998), Development of an AFLP based linkage map of Ler, Col and Cvi Arabidopsis thaliana ecotypes and construction of a Ler/Cvi recombinant inbred line population

. Plant J. 14(2), 259–271.

Examples

data(multitrait)					# Load dataset
multitrait <- fill.geno(multitrait)                     # impute missing genotype data

result <- mqmscanall(multitrait, logtransform=TRUE)	# Analyse all 24 traits

Determine the number of chromosomes

Description

Determine the number of chromosomes in a cross or map object.

Usage

nchr(object)

Arguments

object

An object of class cross (see read.cross for details) or map (see sim.map for details).

Value

The number of chromosomes in the input.

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, plot.cross, summary.cross, nind, totmar, nmar, nphe

Examples

data(fake.f2)
nchr(fake.f2)
map <- pull.map(fake.f2)
nchr(map)

Determine the number of individuals QTL experiment

Description

Determine the number of individuals in cross object.

Usage

nind(object)

Arguments

object

An object of class cross. See read.cross for details.

Value

The number of individuals in the input cross object.

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, plot.cross, summary.cross, nmar, nchr, totmar, nphe

Examples

data(fake.f2)
nind(fake.f2)

Determine the numbers of markers on each chromosome

Description

Determine the number of markers on each chromosome in a cross or map object.

Usage

nmar(object)

Arguments

object

An object of class cross (see read.cross for details) or map (see sim.map for details).

Value

A vector with the numbers of markers on each chromosome in the input.

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, plot.cross, summary.cross, nind, nchr, totmar, nphe

Examples

data(fake.f2)
nmar(fake.f2)
map <- pull.map(fake.f2)
nmar(map)

Number of missing genotypes

Description

Count the number of missing genotypes for each individual or each marker in a cross.

Usage

nmissing(cross, what=c("ind","mar"))

Arguments

cross

An object of class cross. See read.cross for details.

what

Indicates whether to count missing genotypes for each individual or each marker.

Value

A vector containing the number of missing genotypes for each individual or for each marker.

Author(s)

Karl W Broman, [email protected]

See Also

ntyped, summary.cross, nind, totmar

Examples

data(listeria)

# plot number of missing genotypes for each individual
plot(nmissing(listeria))

# plot number of missing genotypes for each marker
plot(nmissing(listeria, what="mar"))

Determine the number of phenotypes QTL experiment

Description

Determine the number of phenotypes in cross object.

Usage

nphe(object)

Arguments

object

An object of class cross. See read.cross for details.

Value

The number of phenotypes in the input cross object.

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, plot.cross, summary.cross, nmar, nchr, totmar, nind

Examples

data(fake.f2)
nphe(fake.f2)

Transform a vector of quantitative values to the corresponding normal quantiles

Description

Transform a vector of quantitative values to the corresponding normal quantiles (preserving the mean and SD).

Usage

nqrank(x, jitter)

Arguments

x

A numeric vector

jitter

If TRUE, randomly jitter the values to break ties.

Value

A numeric vector; the input x is converted to ranks and then to normal quantiles.

Author(s)

Karl W Broman, [email protected]

See Also

rank, qnorm, transformPheno

Examples

data(hyper)

hyper <- transformPheno(hyper, pheno.col=1, transf=nqrank)

Determine the number of QTL in a QTL object

Description

Determine the number of QTL in a QTL object.

Usage

nqtl(qtl)

Arguments

qtl

An object of class qtl. See makeqtl for details.

Value

The number of QTL in the input QTL object.

Author(s)

Karl W Broman, [email protected]

See Also

makeqtl, fitqtl, dropfromqtl, replaceqtl, addtoqtl, summary.qtl, reorderqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c("1", "6", "13")
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

nqtl(qtl)

Number of genotypes

Description

Count the number of genotypes for each individual or each marker in a cross.

Usage

ntyped(cross, what=c("ind","mar"))

Arguments

cross

An object of class cross. See read.cross for details.

what

Indicates whether to count genotypes for each individual or each marker.

Value

A vector containing the number of genotypes for each individual or for each marker.

Author(s)

Karl W Broman, [email protected]

See Also

nmissing, summary.cross, nind, totmar

Examples

data(listeria)

# plot number of genotypes for each individual
plot(ntyped(listeria))

# plot number of genotypes for each marker
plot(ntyped(listeria, what="mar"))

Identify markers without any genotype data

Description

Identify markers in a cross that have no genotype data.

Usage

nullmarkers(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Value

Marker names (a vector of character strings) with no genotype data.

Author(s)

Karl W Broman, [email protected]

See Also

drop.nullmarkers

Examples

# one marker with no data
data(hyper)
nullmarkers(hyper)

# nothing in listeria
data(listeria)
nullmarkers(listeria)

Find an initial order for markers within chromosomes

Description

Establish initial orders for markers within chromosomes by a greedy algorithm, adding one marker at a time with locations of previous markers fixed, in the position giving the miniminum number of obligate crossovers.

Usage

orderMarkers(cross, chr, window=7, use.ripple=TRUE, error.prob=0.0001,
             map.function=c("haldane","kosambi","c-f","morgan"),
             maxit=4000, tol=1e-4, sex.sp=TRUE, verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

window

If use.ripple=TRUE, this indicates the number of markers to include in the sliding window of permuted markers. Larger numbers result in the comparison of a greater number of marker orders, but will require a considerable increase in computation time.

use.ripple

If TRUE, the initial order is refined by a call to the function ripple.

error.prob

Assumed genotyping error rate used in the final estimated map.

map.function

Indicates the map function to use in the final estimated map.

maxit

Maximum number of EM iterations to perform in the final estimated map.

tol

Tolerance for determining convergence in the final estimated map.

sex.sp

Indicates whether to estimate sex-specific maps in the final estimated map; this is used only for the 4-way cross.

verbose

If TRUE, information about the progress of the calculations is displayed; if > 1, even more information is given.

Details

Markers within a linkage group are considered in order of decreasing number of genotyped individuals. The first two markers are placed in an arbitrary order. Additional markers are considered one at a time, and each possible placement of a marker is compared (with the order of the previously placed markers taken as fixed) via the number of obligate crossovers (that is, the minimal number of crossovers that would explain the observed data). The marker is placed in the position giving the minimal number of obligate crossovers. If multiple positions give the same number of obligate crossovers, a single location (among those positions) is chosen at random.

If use.ripple=TRUE, the final order is passed to ripple with method="countxo" to refine the marker order. If use.ripple=TRUE and the number of markers on a chromosome is \le the argument window, the initial greedy algorithm is skipped and all possible marker orders are compared via ripple.

Value

The output is a cross object, as in the input, with orders of markers on selected chromosomes revised.

Author(s)

Karl W Broman, [email protected]

See Also

formLinkageGroups, ripple, est.map, countXO

Examples

data(listeria)
pull.map(listeria, chr=3)
revcross <- orderMarkers(listeria, chr=3, use.ripple=FALSE)
pull.map(revcross, chr=3)

Pull out the phenotypes names from a cross

Description

Pull out the phenotype names from a cross object as a vector.

Usage

phenames(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Value

A vector of character strings (the phenotype names).

Author(s)

Karl W Broman, [email protected]

See Also

markernames, chrnames

Examples

data(listeria)
phenames(listeria)

Identify the largest subset of markers that are some distance apart

Description

Identify the largest subset of markers for which no two adjacent markers are separated by less than some specified distance; if weights are provided, find the marker subset for which the sum of the weights is maximized.

Usage

pickMarkerSubset(locations, min.distance, weights)

Arguments

locations

A vector of marker locations.

min.distance

Minimum distance between adjacent markers in the chosen subset.

weights

(Optional) vector of weights for the markers. If missing, we take weights == 1.

Details

Let did_i be the location of marker ii, for i1,,Mi \in 1, \dots, M. We use the dynamic programming algorithm of Broman and Weber (1999) to identify the subset of markers i1,,iki_1, \dots, i_k for which dij+1dijd_{i_{j+1}} - d_{i_j} \le min.distance and wij\sum w_{i_j} is maximized.

If there are multiple optimal subsets, we pick one at random.

Value

A vector of marker names.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W. and Weber, J. L. (1999) Method for constructing confidently ordered linkage maps. Genet. Epidemiol., 16, 337–343.

See Also

drop.markers, pull.markers, findDupMarkers

Examples

data(hyper)

# subset of markers on chr 4 spaced >= 5 cM
pickMarkerSubset(pull.map(hyper)[[4]], 5)

# no. missing genotypes at each chr 4 marker
n.missing <- nmissing(subset(hyper, chr=4), what="mar")

# weight by -log(prop'n missing), but don't let 0 missing go to +Inf
wts <- -log( (n.missing+1) / (nind(hyper)+1) )

# subset of markers on chr 4 spaced >= 5 cM, with weights = -log(prop'n missing)
pickMarkerSubset(pull.map(hyper)[[4]], 5, wts)

Plot genotype comparison

Description

Plot the results of the comparison of all pairs of individuals' genotypes. A histogram of the proportion of matching genotypes, with tick marks at individual values below, via rug.

Usage

## S3 method for class 'comparegeno'
plot(x, breaks=NULL, main="",
     xlab="Proportion matching genotypes", ...)

Arguments

x

An object of class "comparegeno", as produced by comparegeno.

breaks

Passed to hist, with the default 2n2 \sqrt{n} where nn is the number of pairs of individuals.

main

Title for the plot.

xlab

x-axis label for the plot.

...

Passed to hist.

Details

Creates a histogram with hist with ticks at individual values using rug.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

comparegeno, summary.comparegeno

Examples

data(fake.f2)
cg <- comparegeno(fake.f2)
plot(cg)

Plot various features of a cross object

Description

Plots grid of the missing genotypes, genetic map, and histograms or barplots of phenotypes for the data from an experimental cross.

Usage

## S3 method for class 'cross'
plot(x, auto.layout=TRUE, pheno.col,
          alternate.chrid=TRUE, ...)

Arguments

x

An object of class cross. See read.cross for details.

auto.layout

If TRUE, par(mfrow) is set so that all plots fit within one figure.

pheno.col

Vector of numbers or character strings corresponding to phenotypes that should be plotted. If unspecified, all phenotypes are plotted.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

...

Ignored at this point.

Details

Calls plotMissing, plotMap and plotPheno to plot the missing genotypes, genetic map, and histograms or barplots of all phenotypes.

If auto.format=TRUE, par(mfrow) is used with ceiling(sqrt(n.phe+2)) rows and the minimum number of columns so that all plots fit on the plotting device.

Numeric phenotypes are displayed as histograms or barplots by calling plotPheno.

Value

None.

Author(s)

Karl W Broman, [email protected]; Brian Yandell

See Also

plotMissing, plotMap, plotPheno

Examples

data(fake.bc)
plot(fake.bc)

Plot QTL locations

Description

Plot the locations of the QTL against a genetic map

Usage

## S3 method for class 'qtl'
plot(x, chr, horizontal=FALSE, shift=TRUE,
     show.marker.names=FALSE, alternate.chrid=FALSE, justdots=FALSE,
     col="red", ...)

Arguments

x

An object of class "qtl", as produced by makeqtl.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

horizontal

Specifies whether the chromosomes should be plotted horizontally.

shift

If TRUE, shift the first marker on each chromosome to be at 0 cM.

show.marker.names

If TRUE, marker names are included.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

justdots

If FALSE, just plot dots at the QTL, rather than arrows and QTL names.

col

Color used to plot indications of QTL

...

Passed to plotMap.

Details

Creates a plot, via plotMap, and indicates the locations of the QTL in the input QTL object, x.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

plotMap, makeqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c("1", "6", "13")
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")
plot(qtl)
plot(qtl, justdots=TRUE, col="seagreen")

Plot recombination fractions or LOD scores for a single marker

Description

Plot a slice (corresponding to a single marker) through the pairwise recombination fractions or LOD scores calculated by est.rf and extracted with pull.rf.

Usage

## S3 method for class 'rfmatrix'
plot(x, marker, ...)

Arguments

x

An object of class rfmatrix, as output by pull.rf.

marker

A single marker name, as a character string.

...

Optional arguments passed to plot.scanone.

Value

An object of class "scanone" (as output by scanone, and which may be summarized by summary.scanone or plotted with plot.scanone), containing the estimated recombination fractions or LOD scores for the input marker against all others.

Author(s)

Karl W Broman, [email protected]

See Also

pull.rf, est.rf, plotRF

Examples

data(fake.f2)

fake.f2 <- est.rf(fake.f2)
marker <- markernames(fake.f2, chr=5)[6]
lod <- pull.rf(fake.f2, "lod")
plot(lod, marker, bandcol="gray70")

Plot LOD curves

Description

Plot the LOD curve for a genome scan with a single-QTL model (the output of scanone).

Usage

## S3 method for class 'scanone'
plot(x, x2, x3, chr, lodcolumn=1, incl.markers=TRUE,
     xlim, ylim, lty=1, col=c("black","blue","red"), lwd=2,
     add=FALSE, gap=25, mtick = c("line", "triangle"),
     show.marker.names=FALSE, alternate.chrid=FALSE,
     bandcol=NULL, type="l", cex=1, pch=1, bg="transparent",
     bgrect=NULL, ...)

Arguments

x

An object of class "scanone", as output by scanone.

x2

Optional second scanone object.

x3

Optional third scanone object.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

lodcolumn

An integer, or vector of 3 integers, indicating which of the LOD score columns should be plotted (generally this is 1).

incl.markers

Indicate whether to plot line segments at the marker locations.

xlim

Limits for x-axis (optional).

ylim

Limits for y-axis (optional).

lty

Line types; a vector of length 1 or 3.

col

Line colors; a vector of length 1 or 3.

lwd

Line widths; a vector of length 1 or 3.

add

If TRUE, add to a current plot.

gap

Gap separating chromosomes (in cM).

mtick

Tick mark type for markers (line segments or upward-pointing triangels).

show.marker.names

If TRUE, show the marker names along the x axis.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

bandcol

Optional color for alternating bands to indicate chromosomes. If NULL (the default), no bands are plotted. A good choice might be bandcol="gray70".

type

Type of plot (see plot): for example, type="l" for lines or type="p" for points only, may be of length 1 or 3.

cex

Point size expansion, for example if type="p" is used. May be of length 1 or 3.

pch

Point type, for example if type="p" is used. See points. May be of length 1 or 3.

bg

Background color for points, for example if type="p" and pch=21 are used. See points. May be of length 1 or 3.

bgrect

Optional background color for the rectangular plotting region.

...

Passed to the function plot when it is called.

Details

This function allows you to plot the results of up to three genome scans against one another. Such objects must conform with each other.

One may alternatively use the argument add to add the plot of an additional genome scan to the current figure, but some care is required: the same chromosomes should be selected, and the results must concern crosses with the same genetic maps.

If a single scanone object containing multiple LOD score columns (for example, from different phenotypes) is input, up to three LOD curves may be plotted, by providing a vector in the argument lodcolumn. If multiple scanone objects are input (via x, x2 and x3), the LOD score columns to be plotted are chosen from the corresponding element of the lodcolumn argument.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, summary.scanone, par, colors, add.threshold, xaxisloc.scanone

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2,step=2.5)
out.mr <- scanone(fake.f2, method="mr")
out.em <- scanone(fake.f2, method="em")
plot(out.mr)
plot(out.mr, out.em, chr=c(1,13), lty=1, col=c("violetred","black"))
out.hk <- scanone(fake.f2, method="hk")
plot(out.hk, chr=c(1,13), add=TRUE, col="slateblue")

plot(out.hk, chr=13, show.marker.names=TRUE)

plot(out.hk, bandcol="gray70")

# plot points rather than lines
plot(out.hk, bandcol="gray70", type="p", cex=0.3, pch=21, bg="slateblue")

Plot results of bootstrap for QTL position

Description

Plot a histogram of the results of a nonparametric bootstrap to assess uncertainty in QTL position.

Usage

## S3 method for class 'scanoneboot'
plot(x, ...)

Arguments

x

An object of class "scanoneboot", as output by scanoneboot.

...

Passed to the function hist when it is called.

Details

The function plots a histogram of the bootstrap results obtained by scanoneboot. Genetic marker locations are displayed by vertical lines at the bottom of the plot.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, summary.scanoneboot

Examples

data(fake.f2)
fake.f2 <- calc.genoprob(fake.f2, step=1)

## Not run: out.boot <- scanoneboot(fake.f2, chr=13, method="hk")


summary(out.boot)
plot(out.boot)

Plot permutation results for a single-QTL genome scan

Description

Plot a histogram of the permutation results from a single-QTL genome scan.

Usage

## S3 method for class 'scanoneperm'
plot(x, lodcolumn=1, ...)

Arguments

x

An object of class "scanoneperm", as output by scanone when n.perm is specified.

lodcolumn

This indicates the LOD score column to plot. This should be a single number between 1 and the number of LOD columns in the object input.

...

Passed to the function hist when it is called.

Details

The function plots a histogram of the permutation results obtained by scanone when n.perm is specified. If separate permutations were performed for the autosomes and the X chromosome (using perm.Xsp=TRUE), separate histograms are given.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

scanone, summary.scanoneperm

Examples

data(fake.bc)
fake.bc <- calc.genoprob(fake.bc)

operm <- scanone(fake.bc, method="hk", n.perm=100)
plot(operm)

Plot LOD curves from single-QTL scan to map QTL to a phylogenetic tree

Description

Plot the LOD curves for each partition for a genome scan with a single diallelic QTL (the output of scanPhyloQTL).

Usage

## S3 method for class 'scanPhyloQTL'
plot(x, chr, incl.markers=TRUE,
     col, xlim, ylim, lwd=2, gap=25, mtick=c("line", "triangle"),
     show.marker.names=FALSE, alternate.chrid=FALSE, legend=TRUE, ...)

Arguments

x

An object of class "scanPhyloQTL", as output by scanPhyloQTL.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

incl.markers

Indicate whether to plot line segments at the marker locations.

col

Optional vector of colors to use for each partition.

xlim

Limits for x-axis (optional).

ylim

Limits for y-axis (optional).

lwd

Line width.

gap

Gap separating chromosomes (in cM).

mtick

Tick mark type for markers (line segments or upward-pointing triangels).

show.marker.names

If TRUE, show the marker names along the x axis.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

legend

Indicates whether to include a legend in the plot.

...

Passed to the function plot.scanone when it is called.

Value

None.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Kim, S., An\'e, C. and Payseur, B. A. Mapping quantitative trait loci to a phylogenetic tree. In preparation.

See Also

scanPhyloQTL, max.scanPhyloQTL, summary.scanPhyloQTL, plot.scanone, inferredpartitions, simPhyloQTL, par, colors

Examples

## Not run: 
# example map; drop X chromosome
data(map10)
map10 <- map10[1:19]

# simulate data
x <- simPhyloQTL(4, partition="AB|CD", crosses=c("AB", "AC", "AD"),
                 map=map10, n.ind=150,
                 model=c(1, 50, 0.5, 0))

# run calc.genoprob on each cross
x <- lapply(x, calc.genoprob, step=2)

# scan genome, at each position trying all possible partitions
out <- scanPhyloQTL(x, method="hk")

# maximum peak
max(out, format="lod")

# approximate posterior probabilities at peak
max(out, format="postprob")

# all peaks above a threshold for LOD(best) - LOD(2nd best)
summary(out, threshold=1, format="lod")

# all peaks above a threshold for LOD(best), showing approx post'r prob
summary(out, format="postprob", threshold=3)

# plot of results
plot(out)

## End(Not run)

Plot LOD scores for a two-dimensional genome scan

Description

Plot the results of a two-dimensional, two-QTL genome scan.

Usage

## S3 method for class 'scantwo'
plot(x, chr, incl.markers=FALSE, zlim, lodcolumn=1,
     lower = c("full", "add", "cond-int", "cond-add", "int"),
     upper = c("int", "cond-add", "cond-int", "add", "full"),
     nodiag=TRUE, contours=FALSE, main, zscale=TRUE, point.at.max=FALSE,
     col.scheme = c("viridis", "redblue","cm","gray","heat","terrain","topo"),
     gamma=0.6, allow.neg=FALSE, alternate.chrid=FALSE, ...)

Arguments

x

An object of class "scantwo", as output by scantwo.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

incl.markers

If FALSE, plot LOD scores on an evenly spaced grid (not including the results at the markers).

zlim

A vector of length 2 (optional), indicating the z limits for the lower-right and upper-left triangles, respectively. If one number is given, the same limits are used for both triangles. If zlim is missing, the maximum limits are used for each.

lodcolumn

If the scantwo results contain LOD scores for multiple phenotypes, this argument indicates which to use in the plot.

lower

Indicates which LOD scores should be plotted in the lower triangle. See the details below.

upper

Indicates which LOD scores should be plotted in the upper triangle. See the details below.

nodiag

If TRUE, suppress the plot of the scanone output (which is normally along the diagonal.)

contours

If TRUE, add a contour to the plot at 1.5-LOD below its maximum, using a call to contour. If a numeric vector, contours are drawn at these values below the maximum LOD.

main

An optional title for the plot.

zscale

If TRUE, a color scale is plotted at the right.

point.at.max

If TRUE, plot an X at the maximum LOD.

col.scheme

Name of color pallet. The default is "viridis"; see Option D at https://bids.github.io/colormap/

gamma

Parameter affecting range of colors when col.scheme="gray" or ="redblue".

allow.neg

If TRUE, allow the plot of negative LOD scores; in this case, the z-limits are symmetric about 0. This option is chiefly to allow a plot of difference between LOD scores from different methods, calculated via -.scantwo.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

...

Ignored at this point.

Details

Uses image to plot a grid of LOD scores. The particular LOD scores plotted in the upper-left and lower-right triangles are selected via upper and lower, respectively. By default, the upper-left triangle contains the epistasis LOD scores ("int"), and the lower-right triangle contains the LOD scores for the full model ("full"). The diagonal contains either all zeros or the main effects LOD scores (from scanone).

The scantwo function calculates, for each pair of putative QTLs, (q1,q2)(q_1,q_2), the likelihood under the null model L0L_0, the likelihood under each of the single-QTL models, L(q1)L(q_1) and L(q2)L(q_2), the likelihood under an additive QTL model, La(q1,q2)L_a(q_1,q_2), and the likelihood under a full QTL model (including QTL-QTL interaction), Lf(q1,q2)L_f(q_1,q_2).

The five possible LOD scores that may be plotted are the following. The epistasis LOD scores ("int") are LODi=log10Lf(q1,q2)log10La(q1,q2)LOD_i = \log_{10} L_f(q_1,q_2) - \log_{10} L_a(q_1,q_2).

The full LOD scores ("full") are LODf=log10Lf(q1,q2)log10L0LOD_f = \log_{10} L_f(q_1,q_2) - \log_{10} L_0.

The additive LOD scores ("add") are LODa=log10La(q1,q2)log10L0LOD_a = \log_{10} L_a(q_1,q_2) - \log_{10} L_0.

In addition, we may calculate, for each pair of chromosomes, the difference between the full LOD score and the maximum single-QTL LOD scores for that pair of chromosomes ("cond-int").

Finally, we may calculate, for each pair of chromosomes, the difference between the additive LOD score and the maximum single-QTL LOD scores for that pair of chromosomes ("cond-add").

If a color scale is plotted (zscale=TRUE), the axis on the left indicates the scale for the upper-left triangle, while the axis on the right indicates the scale for the lower-right triangle. Note that the axis labels can get screwed up if you change the size of the figure window; you'll need to redo the plot.

Value

None.

Output of addpair

Note that, for output from addpair in which the new loci are indicated explicitly in the formula, the summary provided by plot.scantwo is somewhat special. In particular, the lower and upper arguments are ignored.

In the case that the formula used in addpair was not symmetric in the two new QTL, the x-axis in the plot corresponds to the first of the new QTL and the y-axis corresponds to the second of the new QTL.

Author(s)

Hao Wu; Karl W Broman, [email protected]; Brian Yandell

See Also

scantwo, summary.scantwo, plot.scanone, -.scantwo

Examples

data(hyper)

hyper <- calc.genoprob(hyper, step=5)


# 2-d scan by EM and by Haley-Knott regression
out2.em <- scantwo(hyper, method="em")
out2.hk <- scantwo(hyper, method="hk")

# plot epistasis and full LOD scores
plot(out2.em)

# plot cond-int in upper triangle and full in lower triangle
#     for chromosomes 1, 4, 6, 15
plot(out2.em, upper="cond-int", chr=c(1,4,6,15))

# plot cond-add in upper triangle and add in lower triangle
#     for chromosomes 1, 4
plot(out2.em, upper="cond-add", lower="add", chr=c(1,4))

# plot the differences between the LOD scores from Haley-Knott
#     regression and the EM algorithm
plot(out2.hk - out2.em, allow.neg=TRUE)

Plot permutation results for a 2d, 2-QTL genome scan

Description

Plot a histogram of the permutation results from a two-dimensional, two-QTL genome scan.

Usage

## S3 method for class 'scantwoperm'
plot(x, lodcolumn=1, include_rug=TRUE, ...)

Arguments

x

An object of class "scantwoperm", as output by scantwo when n.perm is specified.

lodcolumn

This indicates the LOD score column to plot. This should be a single number between 1 and the number of LOD columns in the object input.

include_rug

If TRUE, include a call to rug.

...

Passed to the function hist when it is called.

Details

The function plots a histogram of the permutation results obtained by scantwo when n.perm is specified. Separate histograms are provided for the five LOD scores, full, fv1, int, add, and av1.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, summary.scantwoperm

Examples

data(fake.bc)
fake.bc <- calc.genoprob(fake.bc)

operm2 <- scantwo(fake.bc, method="hk", n.perm=10)
plot(operm2)

Plot grid of error LOD values

Description

Plot a grid of the LOD scores indicating which genotypes are likely to be in error.

Usage

plotErrorlod(x, chr, ind, breaks=c(-Inf,2,3,4.5,Inf),
              col=c("white","gray85","hotpink","purple3"),
              alternate.chrid=FALSE, ...)

Arguments

x

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to be drawn in the plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

ind

Indicates the individuals for which the error LOD scores should be plotted (passed to subset.cross).

breaks

A set of breakpoints for the colors; must give one more breakpoint than color. Intervals are open on the left and closed on the right, except for the lowest interval.

col

A vector of colors to appear in the image.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

...

Ignored at this point.

Details

Uses image to plot a grid with different shades of pixels to indicate which genotypes are likely to be in error.

Darker pixels have higher error LOD scores: LOD2LOD \le 2 in white; 2<LOD32 < LOD \le 3 in gray; 3<LOD4.53 < LOD \le 4.5 in pink; LOD>4.5LOD > 4.5 in purple.

Value

None.

Author(s)

Karl W Broman, [email protected]

References

Lincoln, S. E. and Lander, E. S. (1992) Systematic detection of errors in genetic linkage data. Genomics 14, 604–610.

See Also

calc.errorlod, top.errorlod, image, subset.cross, plotGeno

Examples

data(hyper)

# Calculate error LOD scores
hyper <- calc.errorlod(hyper,error.prob=0.01)

# plot the error LOD scores; print those above a specified cutoff
plotErrorlod(hyper)
plotErrorlod(hyper,chr=1)

Plot observed genotypes, flagging likely errors

Description

Plot the genotypes on a particular chromosome for a set of individuals, flagging likely errors.

Usage

plotGeno(x, chr, ind, include.xo=TRUE, horizontal=TRUE,
          cutoff=4, min.sep=2, cex=1.2, ...)

Arguments

x

An object of class cross. See read.cross for details.

chr

The chromosome to plot. Only one chromosome is allowed. (This should be a character string referring to the chromosomes by name.)

ind

Vector of individuals to plot (passed to subset.cross). If missing, all individuals are plotted.

include.xo

If TRUE, plot X's in intervals having a crossover. Not available for a 4-way cross.

horizontal

If TRUE, chromosomes are plotted horizontally.

cutoff

Genotypes with error LOD scores above this value are flagged as possible errors.

min.sep

Markers separated by less than this value (as a percent of the chromosome length) are pulled apart, so that they may be distinguished in the picture.

cex

Character expansion for the size of points in the plot. Larger numbers give larger points; see par.

...

Ignored at this point.

Details

Plots the genotypes for a set of individuals. Likely errors are indicated by red squares. In a backcross, genotypes AA and AB are indicated by white and black circles, respectively. In an intercross, genotypes AA, AB and BB are indicated by white, gray, and black circles, respectively, and the partially missing genotypes "not BB" (D in mapmaker) and "not AA" (C in mapmaker) are indicated by green and orange circles, respectively.

For the X chromosome in a backcross or intercross, hemizygous males are plotted as if they were homozygous (that is, with white and black circles).

For a 4-way cross, two lines are plotted for each individual. The left or upper line indicates the allele A (white) or B (black); the right or lower line indicates the allele C (white) or D (black). For the case that genotype is known to be only AC/BD or AD/BC, we use green and orange, respectively.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

calc.errorlod, top.errorlod, subset.cross

Examples

data(hyper)

# Calculate error LOD scores
hyper <- calc.errorlod(hyper,error.prob=0.01)

# print those above a specified cutoff
top.errorlod(hyper,cutoff=4)

# plot genotype data, flagging genotypes with error LOD > cutoff
plotGeno(hyper, chr=1, ind=160:200, cutoff=7, min.sep=2)

Plot the proportion of missing genotype information

Description

Plot a measure of the proportion of missing information in the genotype data.

Usage

plotInfo(x, chr, method=c("entropy","variance","both"), step=1,
          off.end=0, error.prob=0.001,
          map.function=c("haldane","kosambi","c-f","morgan"),
          alternate.chrid=FALSE, fourwaycross=c("all", "AB", "CD"),
          include.genofreq=FALSE, ...)

Arguments

x

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

method

Indicates whether to plot the entropy version of the information, the variance version, or both.

step

Maximum distance (in cM) between positions at which the missing information is calculated, though for step=0, it is are calculated only at the marker locations.

off.end

Distance (in cM) past the terminal markers on each chromosome to which the genotype probability calculations will be carried.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi or Carter-Falconer map function when converting genetic distances into recombination fractions.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

fourwaycross

For a phase-known four-way cross, measure missing genotype information overall ("all"), or just for the alleles from the first parent ("AB") or from the second parent ("CD").

include.genofreq

If TRUE, estimated genotype frequencies (from the results of calc.genoprob averaged across the individuals) are included as additional columns in the output.

...

Passed to plot.scanone.

Details

The entropy version of the missing information: for a single individual at a single genomic position, we measure the missing information as H=gpglogpg/lognH = \sum_g p_g \log p_g / \log n, where pgp_g is the probability of the genotype gg, and nn is the number of possible genotypes, defining 0log0=00 \log 0 = 0. This takes values between 0 and 1, assuming the value 1 when the genotypes (given the marker data) are equally likely and 0 when the genotypes are completely determined. We calculate the missing information at a particular position as the average of HH across individuals. For an intercross, we don't scale by logn\log n but by the entropy in the case of genotype probabilities (1/4, 1/2, 1/4).

The variance version of the missing information: we calculate the average, across individuals, of the variance of the genotype distribution (conditional on the observed marker data) at a particular locus, and scale by the maximum such variance.

Calculations are done in C (for the sake of speed in the presence of little thought about programming efficiency) and the plot is created by a call to plot.scanone.

Note that summary.scanone may be used to display the maximum missing information on each chromosome.

Value

An object with class scanone: a data.frame with columns the chromosome IDs and cM positions followed by the entropy and/or variance version of the missing information.

Author(s)

Karl W Broman, [email protected]

See Also

plot.scanone, plotMissing, calc.genoprob, geno.table

Examples

data(hyper)

plotInfo(hyper,chr=c(1,4))

# save the results and view maximum missing info on each chr
info <- plotInfo(hyper)
summary(info)

plotInfo(hyper, bandcol="gray70")

Plot 1-d LOD profiles for a multiple QTL model

Description

Use the results of refineqtl to plot one-dimensional LOD profiles for each QTL.

Usage

plotLodProfile(qtl, chr, incl.markers=TRUE, gap=25, lwd=2, lty=1, col="black",
               qtl.labels=TRUE, mtick=c("line", "triangle"),
               show.marker.names=FALSE, alternate.chrid=FALSE,
               add=FALSE, showallchr=FALSE, labelsep=5, ...)

Arguments

qtl

An object of class "qtl"; must have been produced by refineqtl using keeplodprofiles=TRUE.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

incl.markers

Indicate whether to plot line segments at the marker locations.

gap

Gap separating chromosomes (in cM).

lwd

Line widths for each QTL trace (length 1 or the number of QTL).

lty

Line types for each QTL trace (length 1 or the number of QTL).

col

Line col for each QTL trace (length 1 or the number of QTL).

qtl.labels

If TRUE, place a label on each QTL trace.

mtick

Tick mark type for markers (line segments or upward-pointing triangels).

show.marker.names

If TRUE, show the marker names along the x axis.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

add

If TRUE, add curves to a current plot.

showallchr

If FALSE (the default), only show the chr with a QTL

labelsep

If qtl.labels=TRUE, separation between peak LOD and QTL label, as percent of the height of the plot.

...

Passed to the function plot when it is called.

Details

The function plots LOD profiles in the context of a multiple QTL model, using a scheme best described in Zeng et al. (2000). The position of each QTL is varied, keeping all other loci fixed. If a QTL is isolated on a chromosome, the entire chromosome is scanned; if there are additional linked QTL, the position of a QTL is scanned over the largest interval possible without allowing the order of QTLs along a chromosome to change. At each position for the QTL being scanned, we calculate a LOD score comparing the full model, with the QTL of interest at that particular position (and all others at their fixed positions) to the model with the QTL of interest (and any interactions that include that QTL) omitted.

Care should be take regarding the arguments lwd, lty, and col; if vectors are given, they should be in the order of the QTL within the object, which may be different than the order in which they are plotted. (The LOD profiles are sorted by chromosome and position.)

Value

None.

Author(s)

Karl W Broman, [email protected]

References

Zeng Z.-B., Liu, J., Stam, L. F., Kao, C.-H., Mercer, J. M. and Laurie, C. C. (2000) Genetic architecture of a morphological shape difference between two Drosophila species. Genetics 154, 299–310.

See Also

refineqtl, makeqtl, scanqtl

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=2)
qtl <- makeqtl(fake.bc, chr=c(2,5), pos=c(32.5, 17.5), what="prob")

out <- scanone(fake.bc, method="hk")

# refine QTL positions and keep LOD profiles
rqtl <- refineqtl(fake.bc, qtl=qtl, method="hk", keeplodprofile=TRUE)

# plot the LOD profiles
plotLodProfile(rqtl)

# add the initial scan results, for comparison
plot(out, add=TRUE, chr=c(2,5), col="red")

Plot genetic map

Description

Plot genetic map of marker locations for all chromosomes.

Usage

## S3 method for class 'map'
plot(x, map2, chr, horizontal=FALSE, shift=TRUE,
     show.marker.names=FALSE, alternate.chrid=FALSE, ...)
plotMap(x, map2, chr, horizontal=FALSE, shift=TRUE,
     show.marker.names=FALSE, alternate.chrid=FALSE, ...)

Arguments

x

A list whose components are vectors of marker locations. A cross object may be given instead, in which case the genetic map it contains is used.

map2

An optional second genetic map with the same number (and names) of chromosomes. As with the first argument, a cross object may be given instead. If this argument is given, a comparison of the two genetic maps is plotted.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

horizontal

Specifies whether the chromosomes should be plotted horizontally.

shift

If TRUE, shift the first marker on each chromosome to be at 0 cM.

show.marker.names

If TRUE, marker names are included.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

...

Passed to plot.

Details

Plots the genetic map for each chromosome, or a comparison of the genetic maps if two maps are given.

For a comparison of two maps, the first map is on the left (or, if horizontal=TRUE, on the top). Lines are drawn to connect markers. Markers that exist in just one map and not the other are indicated by short line segments, on one side or the other, that are not connected across.

For a sex-specific map, female and male maps are plotted against one another. For two sex-specific maps, the two female maps are plotted against one another and the two male maps are plotted against one another.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

est.map, plot.cross

Examples

data(fake.bc)

plotMap(fake.bc)
plotMap(fake.bc,horizontal=TRUE)

newmap <- est.map(fake.bc)
plot(newmap)
plotMap(fake.bc, newmap)

plotMap(fake.bc, show.marker.names=TRUE)

Plot grid of missing genotypes

Description

Plot a grid showing which genotypes are missing.

Usage

plotMissing(x, chr, reorder=FALSE, main="Missing genotypes",
             alternate.chrid=FALSE, ...)

Arguments

x

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

reorder

Specify whether to reorder individuals according to their phenotypes.

FALSE Don't reorder
TRUE Reorder according to the sum of the phenotypes
n Reorder according to phenotype n
main

Title to place on plot.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

...

Ignored at this point.

Details

Uses image to plot a grid with black pixels where the genotypes are missing. For intercross and 4-way cross data, gray pixels are plotted for the partially missing genotypes (for example, "not AA").

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

plot.cross, geno.image, image

Examples

data(fake.f2)
plotMissing(fake.f2)

Plot a QTL model

Description

Plot a graphical representation of a QTL model, with nodes representing QTL and line segments representing pairwise interactions.

Usage

plotModel(qtl, formula, circrad.rel=0.25, circrad.abs,
         cex.name=1, chronly=FALSE, order, ...)

Arguments

qtl

A QTL object (as created by makeqtl) or vector of character strings indicating the names for the QTL. This is also allowed to be a list that contains a component named "chr" (and, optionally, components names "pos" and "formula").

formula

Optional formula defining the QTL model. If missing, we look for an attribute "formula" to the input QTL object or a item named "formula" within the QTL object.

circrad.rel

Radius of the circles that indicate the QTL, relative to the distance between the circles.

circrad.abs

Optional radius of the circles that indicate the QTL; note that the plotting region will have x- and y-axis limits spanning 3 units.

cex.name

Character expansion for the QTL names.

chronly

If TRUE and a formal QTL object is given, only the chromosome IDs are used to identify the QTL.

order

Optional vector indicating a permutation of the QTL to define where they are to appear in the plot. QTL are placed around a circle, starting at the top and going clockwise.

...

Passed to the function plot.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

stepwiseqtl, makeqtl

Examples

# plot a QTL model, using a vector of character strings to define the QTL
plotModel(c("1","4","6","15"), formula=y~Q1+Q2+Q3*Q4)

# plot an additive QTL model
data(hyper)
hyper <- calc.genoprob(hyper)
qtl <- makeqtl(hyper, chr=c(1,4,6,15), pos=c(68.3,30,60,18), what="prob")
plotModel(qtl)

# include an interaction
plotModel(qtl, formula=y~Q1+Q2+Q3*Q4)

# alternatively, include the formula as an attribute to the QTL object
attr(qtl, "formula") <- y~Q1+Q2+Q3*Q4
plotModel(qtl)

# if formula given, the attribute within the object is ignored
plotModel(qtl, y~Q1+Q2+Q3+Q4)

# NULL formula indicates additive QTL model
plotModel(qtl, NULL)

# reorder the QTL in the figure
plotModel(qtl, order=c(1,3,4,2))

# show just the chromosome numbers
plotModel(qtl, chronly=TRUE)

Plot a phenotype distribution

Description

Plots a histogram or barplot of the data for a phenotype from an experimental cross.

Usage

plotPheno(x, pheno.col=1, ...)

Arguments

x

An object of class cross. See read.cross for details.

pheno.col

The phenotype column to plot: a numeric index, or the phenotype name as a character string. Alternatively, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

...

Passed to hist or barplot.

Details

Numeric phenotypes are displayed as histograms with approximately 2n2\sqrt{n} bins. Phenotypes that are factors or that have very few unique values are displayed as barplots.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

plot.cross, plotMap, plotMissing, hist, barplot

Examples

data(fake.bc)
plotPheno(fake.bc, pheno.col=1)
plotPheno(fake.bc, pheno.col=3)
plotPheno(fake.bc, pheno.col="age")

Plot phenotypes versus marker genotypes

Description

Plot the phenotype values versus the genotypes at a marker or markers.

Usage

plotPXG(x, marker, pheno.col=1, jitter=1, infer=TRUE,
         pch, ylab, main, col, ...)

Arguments

x

An object of class cross. See read.cross for details.

marker

Marker name (a character string; can be a vector).

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

jitter

A positive number indicating how much to spread out the points horizontally. (Larger numbers correspond to greater spread.)

infer

If TRUE, missing genotypes are filled in with a single random imputation and plotted in red; if FALSE, only individuals typed at the specified marker are plotted.

pch

Plot symbol.

ylab

Label for y-axis.

main

Main title for the plot. If missing, the names of the markers are used.

col

A vector of colors to use for the confidence intervals (optional).

...

Passed to plot.

Details

Plots the phenotype data against the genotypes at the specified marker. If infer=TRUE, the genotypes of individuals that were not typed is inferred based the genotypes at linked markers via a single imputation from sim.geno; these points are plotted in red. For each genotype, the phenotypic mean is plotted, with error bars at ±\pm 1 SE.

Value

A data.frame with initial columns the marker genotypes, then the phenotype data, then a column indicating whether any of the marker genotypes were inferred (1=at least one genotype inferred, 0=none were inferred).

Author(s)

Karl W Broman, [email protected]; Brian Yandell

See Also

find.marker, effectplot, find.flanking, effectscan

Examples

data(listeria)
mname <- find.marker(listeria, 5, 28) # marker D5M357
plotPXG(listeria, mname)

mname2 <- find.marker(listeria, 13, 26) # marker D13Mit147
plotPXG(listeria, c(mname, mname2))
plotPXG(listeria, c(mname2, mname))

# output of the function contains the raw data
output <- plotPXG(listeria, mname)
head(output)

# another example
data(fake.f2)
mname <- find.marker(fake.f2, 1, 37) # marker D1M437
plotPXG(fake.f2, mname)

mname2 <- find.marker(fake.f2, "X", 14) # marker DXM66
plotPXG(fake.f2, mname2)

plotPXG(fake.f2, c(mname,mname2))
plotPXG(fake.f2, c(mname2,mname))

Plot recombination fractions

Description

Plot a grid showing the recombination fractions for all pairs of markers, and/or the LOD scores for tests of linkage between pairs of markers.

Usage

plotRF(x, chr, what=c("both","lod","rf"), alternate.chrid=FALSE,
        zmax=12, mark.diagonal=FALSE,
        col.scheme=c("viridis", "redblue"), ...)

Arguments

x

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to plot. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

what

Indicate whether to plot LOD scores, recombination fractions or both.

alternate.chrid

If TRUE and more than one chromosome is plotted, alternate the placement of chromosome axis labels, so that they may be more easily distinguished.

zmax

Maximum LOD score plotted; values above this are all thresholded at this value.

mark.diagonal

If TRUE, include black line segments around the pixels along the diagonal, to better separate the upper left triangle from the lower right triangle.

col.scheme

The color palette. The default is "viridis"; see Option D at https://bids.github.io/colormap/

...

Generally ignored, but you can include main to change or omit the title of the figure.

Details

Uses image to plot a grid showing the recombination fractions and/or LOD scores for all pairs of markers. (The LOD scores are for a test of r=1/2r = 1/2.) If both are plotted, the recombination fractions are in the upper left triangle while the LOD scores are in the lower right triangle.

With col.scheme="viridis" (the default), purple corresponds to a large LOD score or a small recombination fraction, while yellow is the reverse. With col.scheme="redblue", red corresponds to a large LOD or a small recombination fraction, while blue is the reverse. Note that missing values appear in light gray.

Recombination fractions are transformed by 4(log2r+1)-4(\log_2{r}+1) to make them on the same sort of scale as LOD scores. Values of LOD or the transformed recombination fraction that are above 12 are set to 12.

Value

None.

Author(s)

Karl W Broman, [email protected]

See Also

est.rf, pull.rf, plot.rfmatrix, image, badorder, ripple

Examples

data(badorder)
badorder <- est.rf(badorder)
plotRF(badorder)

# plot just chr 1
plotRF(badorder, chr=1)

# plot just the recombination fractions
plotRF(badorder, what="rf")

# plot just the LOD scores, and just for chr 2 and 3
plotRF(badorder, chr=2:3, what="lod")

Pull out the results of the Viterbi algorithm from a cross

Description

Pull out the results of argmax.geno from a cross as a matrix.

Usage

pull.argmaxgeno(cross, chr, include.pos.info=FALSE, rotate=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

include.pos.info

If TRUE, include columns with marker name, chromosmoe ID, and cM position. (If include.pos.info=TRUE, we take rotate=TRUE.)

rotate

If TRUE, return matrix with individuals as columns and positions as rows. If FALSE, rows correspond to individuals.

Value

A matrix containing numeric indicators of the inferred genotypes. Multiple chromosomes are pasted together.

Author(s)

Karl W Broman, [email protected]

See Also

pull.geno, pull.genoprob, pull.draws, argmax.geno

Examples

data(listeria)
listeria <- argmax.geno(listeria, step=1, stepwidth="max")
amg <- pull.argmaxgeno(listeria, chr=c(5,13), include.pos.info=TRUE, rotate=TRUE)
amg[1:5,1:10]

Pull out the genotype imputations from a cross

Description

Pull out the results of sim.geno from a cross as an array.

Usage

pull.draws(cross, chr)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

Value

An array containing numeric indicators of the imputed genotypes. Multiple chromosomes are pasted together. The dimensions are individuals by positions by imputations

Author(s)

Karl W Broman, [email protected]

See Also

pull.geno, pull.genoprob, pull.argmaxgeno, sim.geno

Examples

data(listeria)
listeria <- sim.geno(listeria, step=5, stepwidth="max", n.draws=8)
dr <- pull.draws(listeria, chr=c(5,13))
dr[1:20,1:10,1]

Pull out the genotype data from a cross

Description

Pull out the genotype data from a cross object, as a single big matrix.

Usage

pull.geno(cross, chr)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

Value

A matrix of size n.ind x tot.mar. The raw genotype data in the input cross object, with the chromosomes pasted together.

Author(s)

Karl W Broman, [email protected]

See Also

pull.pheno, pull.map pull.draws, pull.genoprob, pull.argmaxgeno

Examples

data(listeria)
dat <- pull.geno(listeria)

# image of the genotype data
image(1:ncol(dat),1:nrow(dat),t(dat),ylab="Individuals",xlab="Markers",
      col=c("red","yellow","blue","green","violet"))
abline(v=cumsum(c(0,nmar(listeria)))+0.5)
abline(h=nrow(dat)+0.5)

Pull out the genotype probabilities from a cross

Description

Pull out the results of calc.genoprob from a cross as a matrix.

Usage

pull.genoprob(cross, chr, omit.first.prob=FALSE,
              include.pos.info=FALSE, rotate=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

omit.first.prob

If TRUE, omit the probabilities for the first genotype at each position (since they sum to 1).

include.pos.info

If TRUE, include columns with marker name, genotype, chromosome ID, and cM position. (If include.pos.info=TRUE, we take rotate=TRUE.)

rotate

If TRUE, return matrix with individuals as columns and positions/genotypes as rows. If FALSE, rows correspond to individuals.

Value

A matrix containing genotype probabilities. Multiple chromosomes and the multiple genotypes at each position are pasted together.

Author(s)

Karl W Broman, [email protected]

See Also

pull.geno, pull.argmaxgeno, pull.draws, calc.genoprob

Examples

data(listeria)
listeria <- calc.genoprob(listeria, step=1, stepwidth="max")
pr <- pull.genoprob(listeria, chr=c(5,13), omit.first.prob=TRUE, include.pos.info=TRUE, rotate=TRUE)
pr[1:5,1:10]

Pull out the genetic map from a cross

Description

Pull out the map portion of a cross object.

Usage

pull.map(cross, chr, as.table=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

as.table

If TRUE, return the genetic map as a table with chromosome assignments and marker names. If FALSE, return the map as a "map" object.

Value

The genetic map: a list with each component containing the marker positions (in cM) for a chromosome. Each component has class A or X according to whether it is an autosome or the X chromosome. The components are either vectors of marker positions or, for a sex-specific map, 2-row matrices containing the female and male marker locations. The map itself is given class map.

Author(s)

Karl W Broman, [email protected]

See Also

replace.map, plotMap, map2table

Examples

data(fake.f2)
map <- pull.map(fake.f2)
plot(map)

Drop all but a selected set of markers

Description

Drop all but a selected set of markers from the data matrices and genetic maps.

Usage

pull.markers(cross, markers)

Arguments

cross

An object of class cross. See read.cross for details.

markers

A character vector of marker names.

Value

The input object, with any markers not specified in the vector markers removed from the genotype data matrices, genetic maps, and, if applicable, any derived data (such as produced by calc.genoprob). (It might be a good idea to re-derive such things after using this function.)

Author(s)

Karl W Broman, [email protected]

See Also

drop.nullmarkers, drop.markers, geno.table, clean.cross

Examples

data(listeria)
listeria2 <- pull.markers(listeria, c("D10M44","D1M3","D1M75"))

Pull out phenotype data from a cross

Description

Pull out selected phenotype data from a cross object, as a data frame or vector.

Usage

pull.pheno(cross, pheno.col)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

A vector specifying which phenotypes to keep or discard. This may be a logical vector, a numeric vector, or a vector of character strings (for the phenotype names). If missing, the entire set of phenotypes is output.

Value

A data.frame with columns specifying phenotypes and rows specifying individuals. If there is just one phenotype, a vector (rather than a data.frame) is returned.

Author(s)

Karl W Broman, [email protected]

See Also

pull.geno, pull.map

Examples

data(listeria)
pull.pheno(listeria, "sex")

Pull out recombination fractions or LOD scores from a cross object

Description

Pull out either the pairwise recombination fractions or the LOD scores, as calculated by est.rf, from a cross object.

Usage

pull.rf(cross, what=c("rf", "lod"), chr)

Arguments

cross

An object of class cross. See read.cross for details.

what

Indicates whether to pull out a matrix of estimated recombination fractions or a matrix of LOD scores.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

Value

An object of class "rfmatrix", which is a matrix of either estimated recombination fractions between all marker pairs or of LOD scores (for the test of rf=1/2) for all marker pairs.

The genetic map is included as an attribute.

Author(s)

Karl W Broman, [email protected]

See Also

est.rf, plot.rfmatrix, plotRF

Examples

data(fake.f2)

fake.f2 <- est.rf(fake.f2)
rf <- pull.rf(fake.f2)
lod <- pull.rf(fake.f2, "lod")
plot(rf[1,], lod[1,], xlab="rec frac", ylab="LOD score")
marker <- markernames(fake.f2, chr=5)[6]
par(mfrow=c(2,1))
plot(rf, marker, bandcol="gray70")
plot(lod, marker, bandcol="gray70")

Installed version of R/qtl

Description

Print the version number of the currently installed version of R/qtl.

Usage

qtlversion()

Value

A character string with the version number of the currently installed version of R/qtl.

Author(s)

Karl W Broman, [email protected]

Examples

qtlversion()

Read data for a QTL experiment

Description

Data for a QTL experiment is read from a set of files and converted into an object of class cross. The comma-delimited format (csv) is recommended. All formats require chromosome assignments for the genetic markers, and assume that markers are in their correct order.

Usage

read.cross(format=c("csv", "csvr", "csvs", "csvsr", "mm", "qtx",
                    "qtlcart", "gary", "karl", "mapqtl", "tidy"),
           dir="", file, genfile, mapfile, phefile, chridfile,
           mnamesfile, pnamesfile, na.strings=c("-","NA"),
           genotypes=c("A","H","B","D","C"), alleles=c("A","B"),
           estimate.map=FALSE, convertXdata=TRUE, error.prob=0.0001,
           map.function=c("haldane", "kosambi", "c-f", "morgan"),
           BC.gen=0, F.gen=0, crosstype, ...)

Arguments

format

Specifies the format of the data file or files. Details on the various file formats are provided below.

dir

Directory in which the data files will be found. In Windows, use forward slashes ("/") or double backslashes ("\\") to specify directory trees.

file

The main input file for formats csv, csvr and mm.

genfile

File with genotype data (formats csvs, csvsr, karl, gary and mapqtl only).

mapfile

File with marker position information (all except the csv formats).

phefile

File with phenotype data (formats csvs, csvsr, karl, gary and mapqtl only).

chridfile

File with chromosome ID for each marker (gary format only).

mnamesfile

File with marker names (gary format only).

pnamesfile

File with phenotype names (gary format only).

na.strings

A vector of strings which are to be interpreted as missing values (csv and gary formats only). For the csv formats, these are interpreted globally for the entire file, so missing value codes in phenotypes must not be valid genotypes, and vice versa. For the gary format, these are used only for the phenotype data.

genotypes

A vector of character strings specifying the genotype codes (csv formats only). Generally this is a vector of length 5, with the elements corresponding to AA, AB, BB, not BB (i.e., AA or AB), and not AA (i.e., AB or BB). Note: Pay careful attention to the third and fourth of these; the order of these can be confusing.

If you are trying to read 4-way cross data, your file must have genotypes coded as described below, and you need to set genotypes=NULL so that no re-coding gets done.

alleles

A vector of two one-letter character strings (or four, for the four-way cross), to be used as labels for the two alleles.

estimate.map

For all formats but qtlcart, mapqtl, and karl: if TRUE and marker positions are not included in the input files, the genetic map is estimated using the function est.map.

convertXdata

If TRUE, any X chromosome genotype data is converted to the internal standard, using columns sex and pgm in the phenotype data if they available or by inference if they are not. If FALSE, the X chromsome data is read as is.

error.prob

In the case that the marker map must be estimated: Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

In the case that the marker map must be estimated: Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions. (Ignored if m > 0.)

BC.gen

Used only for cross type "bcsft".

F.gen

Used only for cross type "bcsft".

crosstype

Optional character string to force a particular cross type.

...

Additional arguments, passed to the function read.table in the case of csv and csvr formats. In particular, one may use the argument sep to specify the field separator (the default is a comma), dec to specify the character used for the decimal point (the default is a period), and comment.char to specify a character to indicate comment lines.

Details

The available formats are comma-delimited (csv), rotated comma-delimited (csvr), comma-delimited with separate files for genotype and phenotype data (csvs), rotated comma-delimited with separate files for genotype and phenotype data (csvsr), Mapmaker (mm), Map Manager QTX (qtx), Gary Churchill's format (gary), Karl Broman's format (karl) and MapQTL/JoinMap (mapqtl). The required files and their specification for each format appears below. The comma-delimited formats are recommended. Note that most of these formats work only for backcross and intercross data.

The sampledata directory in the package distribution contains sample data files in multiple formats. Also see https://rqtl.org/sampledata/.

The ... argument enables additional arguments to be passed to the function read.table in the case of csv and csvr formats. In particular, one may use the argument sep to specify the field separator (the default is a comma), dec to specify the character used for the decimal point (the default is a period), and comment.char to specify a character to indicate comment lines.

Value

An object of class cross, which is a list with two components:

geno

This is a list with elements corresponding to chromosomes. names(geno) contains the names of the chromsomes. Each chromosome is itself a list, and is given class A or X according to whether it is autosomal or the X chromosome.

There are two components for each chromosome: data, a matrix whose rows are individuals and whose columns are markers, and map, either a vector of marker positions (in cM) or a matrix of dim (2 x n.mar) where the rows correspond to marker positions in female and male genetic distance, respectively.

The genotype data gets converted into numeric codes, as follows.

The genotype data for a backcross is coded as NA = missing, 1 = AA, 2 = AB.

For an F2 intercross, the coding is NA = missing, 1 = AA, 2 = AB, 3 = BB, 4 = not BB (i.e. AA or AB; D in Mapmaker/qtl), 5 = not AA (i.e. AB or BB; C in Mapmaker/qtl).

For a 4-way cross, the mother and father are assumed to have genotypes AB and CD, respectively. The genotype data for the progeny is assumed to be phase-known, with the following coding scheme: NA = missing, 1 = AC, 2 = BC, 3 = AD, 4 = BD, 5 = A = AC or AD, 6 = B = BC or BD, 7 = C = AC or BC, 8 = D = AD or BD, 9 = AC or BD, 10 = AD or BC, 11 = not AC, 12 = not BC, 13 = not AD, 14 = not BD.

pheno

data.frame of size (n.ind x n.phe) containing the phenotypes. If a phenotype with the name id or ID is included, these identifiers will be used in top.errorlod, plotErrorlod, and plotGeno as identifiers for the individual.

While the data format is complicated, there are a number of functions, such as subset.cross, to assist in pulling out portions of the data.

X chromosome

The genotypes for the X chromosome require special care!

The X chromosome should be given chromosome identifier X or x. If it is labeled by a number or by Xchr, it will be interpreted as an autosome.

The phenotype data should contain a column named "sex" which indicates the sex of each individual, either coded as 0=female and 1=male, or as a factor with levels female/male or f/m. Case will be ignored both in the name and in the factor levels. If no such phenotype column is included, it will be assumed that all individuals are of the same sex.

In the case of an intercross, the phenotype data may also contain a column named "pgm" (for "paternal grandmother") indicating the direction of the cross. It should be coded as 0/1 with 0 indicating the cross (AxB)x(AxB) or (BxA)x(AxB) and 1 indicating the cross (AxB)x(BxA) or (BxA)x(BxA). If no such phenotype column is included, it will be assumed that all individuals come from the same direction of cross.

The internal storage of X chromosome data is quite different from that of autosomal data. Males are coded 1=AA and 2=BB; females with pgm==0 are coded 1=AA and 2=AB; and females with pgm==1 are coded 1=BB and 2=AB. If the argument convertXdata is TRUE, conversion to this format is made automatically; if FALSE, no conversion is done, summary.cross will likely return a warning, and most analyses will not work properly.

Use of convertXdata=FALSE (in which case the X chromosome genotypes will not be converted to our internal standard) can be useful for diagnosing problems in the data, but will require some serious mucking about in the internal data structure.

CSV format

The input file is a comma-delimited text file. A different field separator may be specified via the argument sep, which will be passed to the function read.table). For example, in Europe, it is common to use a comma in place of the decimal point in numbers and so a semi-colon in place of a comma as the field separator; such data may be read by using sep=";" and dec=",".

The first line should contain the phenotype names followed by the marker names. At least one phenotype must be included; for example, include a numerical index for each individual.

The second line should contain blanks in the phenotype columns, followed by chromosome identifiers for each marker in all other columns. If a chromosome has the identifier X or x, it is assumed to be the X chromosome; otherwise, it is assumed to be an autosome.

An optional third line should contain blanks in the phenotype columns, followed by marker positions, in cM.

Marker order is taken from the cM positions, if provided; otherwise, it is taken from the column order.

Subsequent lines should give the data, with one line for each individual, and with phenotypes followed by genotypes. If possible, phenotypes are made numeric; otherwise they are converted to factors.

The genotype codes must be the same across all markers. For example, you can't have one marker coded AA/AB/BB and another coded A/H/B. This includes genotypes for the X chromosome, for which hemizygous individuals should be coded as if they were homoyzogous.

The cross is determined to be a backcross if only the first two elements of the genotypes string are found; otherwise, it is assumed to be an intercross.

CSVr format

This is just like the csv format, but rotated (or really transposed), so that rows are columns and columns are rows.

CSVs format

This is like the csv format, but with separate files for the genotype and phenotype data.

The first column in the genotype data must specify individuals' identifiers, and there must be a column in the phenotype data with precisely the same information (and with the same name). These IDs will be included in the data as a phenotype. If the name id or ID is used, these identifiers will be used in top.errorlod, plotErrorlod, and plotGeno as identifiers for the individual.

The first row in each file contains the column names. For the phenotype file, these are the names of the phenotypes. For the genotype file, the first cell will be the name of the identifier column (id or ID) and the subsequent fields will be the marker names.

In the genotype data file, the second row gives the chromosome IDs. The cell in the second row, first column, must be blank. A third row giving cM positions of markers may be included, in which case the cell in the third row, first column, must be blank.

There need be no blank rows in the phenotype data file.

CSVsr format

This is just like the csvs format, but with each file rotated (or really transposed), so that rows are columns and columns are rows.

Mapmaker format

This format requires two files. The so-called rawfile, specified by the argument file, contains the genotype and phenotype data. Rows beginning with the symbol # are ignored. The first line should be either data type f2 intercross or data type f2 backcross. The second line should begin with three numbers indicating the numbers of individuals, markers and phenotypes in the file. This line may include the word symbols followed by symbol assignments (see the documentation for mapmaker, and cross your fingers). The rest of the lines give genotype data followed by phenotype data, with marker and phenotype names always beginning with the * symbol.

A second file contains the genetic map information, specified with the argument mapfile. The map file may be in one of two formats. The function will determine which format of map file is presented.

The simplest format for the map file is not standard for the Mapmaker software, but is easy to create. The file contains two or three columns separated by white space and with no header row. The first column gives the chromosome assignments. The second column gives the marker names, with markers listed in the order along the chromosomes. An optional third column lists the map positions of the markers.

Another possible format for the map file is the .maps format, which is produced by Mapmaker. The code for reading this format was written by Brian Yandell.

Marker order is taken from the map file, either by the order they are presented or by the cM positions, if specified.

Map Manager QTX format

This format requires a single file (that produced by the Map Manager QTX program).

QTL Cartographer format

This format requires two files: the .cro and .map files for QTL Cartographer (produced by the QTL Cartographer sub-program, Rmap and Rcross).

Note that the QTL Cartographer cross types are converted as follows: RF1 to riself, RF2 to risib, RF0 (doubled haploids) to bc, B1 or B2 to bc, RF2 or SF2 to f2.

Tidy format

This format requires three simple CSV files, separating the genotype, phenotype, and marker map information so that each file may be of a simple form.

Gary format

This format requires the six files. All files have default names, and so the file names need not be specified if the default names are used.

genfile (default = "geno.dat") contains the genotype data. The file contains one line per individual, with genotypes for the set of markers separated by white space. Missing values are coded as 9, and genotypes are coded as 0/1/2 for AA/AB/BB.

mapfile (default = "markerpos.txt") contains two columns with no header row: the marker names in the first column and their cM position in the second column. If marker positions are not available, use mapfile=NULL, and a dummy map will be inserted.

phefile (default = "pheno.dat") contains the phenotype data, with one row for each mouse and one column for each phenotype. There should be no header row, and missing values are coded as "-".

chridfile (default = "chrid.dat") contains the chromosome identifier for each marker.

mnamesfile (default = "mnames.txt") contains the marker names.

pnamesfile (default = "pnames.txt") contains the names of the phenotypes. If phenotype names file is not available, use pnamesfile=NULL; arbitrary phenotype names will then be assigned.

Karl format

This format requires three files; all files have default names, and so need not be specified if the default name is used.

genfile (default = "gen.txt") contains the genotype data. The file contains one line per individual, with genotypes separated by white space. Missing values are coded 0; genotypes are coded as 1/2/3/4/5 for AA/AB/BB/not BB/not AA.

mapfile (default = "map.txt") contains the map information, in the following complicated format:

n.chr
n.mar(1) rf(1,1) rf(1,2) ... rf(1,n.mar(1)-1)
mar.name(1,1)
mar.name(1,2)
...
mar.name(1,n.mar(1))
n.mar(2)
...
etc.

phefile (default = "phe.txt") contains a matrix of phenotypes, with one individual per line. The first line in the file should give the phenotype names.

MapQTL format

This format requires three files, described in the manual of the MapQTL program (same as JoinMap).

genfile corresponds to the loc file containing the genotype data. Each marker and its genotypes should be on a single line.

mapfile corresponds to the map file containing the linkage group assignment, marker names and their map positions.

phefile corresponds to the qua file containing the phenotypes.

For the moment, only 4-way crosses are supported (CP population type in MapQTL).

Author(s)

Karl W Broman, [email protected]; Brian S. Yandell; Aaron Wolen

References

Broman, K. W. and Sen, Ś. (2009) A guide to QTL mapping with R/qtl. Springer. https://rqtl.org/book/

See Also

subset.cross, summary.cross, plot.cross, c.cross, clean.cross, write.cross, sim.cross, read.table. The sampledata directory in the package distribution contains sample data files in multiple formats. Also see https://rqtl.org/sampledata/.

Examples

## Not run: 
# CSV format
dat1 <- read.cross("csv", dir="Mydata", file="mydata.csv")

# CSVS format
dat2 <- read.cross("csvs", dir="Mydata", genfile="mydata_gen.csv",
                   phefile="mydata_phe.csv")

# you can read files directly from the internet
datweb <- read.cross("csv", "https://rqtl.org/sampledata",
                     "listeria.csv")

# Mapmaker format
dat3 <- read.cross("mm", dir="Mydata", file="mydata.raw",
                   mapfile="mydata.map")

# Map Manager QTX format
dat4 <- read.cross("qtx", dir="Mydata", file="mydata.qtx")

# QTL Cartographer format
dat5 <- read.cross("qtlcart", dir="Mydata", file="qtlcart.cro",
                   mapfile="qtlcart.map")

# Gary format
dat6 <- read.cross("gary", dir="Mydata", genfile="geno.dat",
                   mapfile="markerpos.txt", phefile="pheno.dat",
                   chridfile="chrid.dat", mnamesfile="mnames.txt",
                   pnamesfile="pnames.txt")

# Karl format
dat7 <- read.cross("karl", dir="Mydata", genfile="gen.txt",
                   phefile="phe.txt", mapfile="map.txt")
## End(Not run)

Read data for 4- or 8-way RIL

Description

Data for a set of 4- or 8-way recombinant inbred lines (RIL) is read from a pair of comma-delimited files and converted into an object of class cross. We require chromosome assignments for the genetic markers, and assume that markers are in their correct order.

Usage

readMWril(dir="", rilfile, founderfile,
          type=c("ri4self", "ri4sib", "ri8self", "ri8selfIRIP1", "ri8sib", "bgmagic16"),
          na.strings=c("-","NA"), rotate=FALSE, ...)

Arguments

dir

Directory in which the data files will be found. In Windows, use forward slashes ("/") or double backslashes ("\\") to specify directory trees.

rilfile

Comma-delimited file for the RIL, in the "csv" format described in the help file for read.cross.

founderfile

File with founder strains' genotypes, in the same orientation as the rilfile, but with just marker names and the founders' marker genotypes.

type

The type of RIL.

na.strings

A vector of strings which are to be interpreted as missing values. For the csv formats, these are interpreted globally for the entire file, so missing value codes in phenotypes must not be valid genotypes, and vice versa. For the gary format, these are used only for the phenotype data.

rotate

If TRUE, the rilfile and founderfile are rotated (really transposed), with rows corresponding to markers and columns corresponding to individuals.

...

Additional arguments, passed to the function read.table in the case of csv and csvr formats. In particular, one may use the argument sep to specify the field separator (the default is a comma) and dec to specify the character used for the decimal point (the default is a period).

Details

The rilfile should include a phenotype cross containing character strings of the form ABCDEFGH, indicating the cross used to generate each RIL. The genotypes should be coded as integers (e.g., 1 and 2).

The founder strains in the founderfile should be the strains A, B, C, ..., as indicated in the cross phenotype.

The default arrangement of the files is to have markers as columns and individuals/founders as rows. If rotate=TRUE, do the opposite: markers as rows and individuals/founders as columns.

Value

An object of class cross; see the help file for read.cross for details.

An additional component crosses is included; this is a matrix indicating the crosses used to generate the RIL.

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, sim.cross

Examples

## Not run: 
ril <- read.cross("../Data", "ril_data.csv", "founder_geno.csv", "ri4self",
                  rotate=TRUE)
## End(Not run)

Reduce to a grid of pseudomarkers.

Description

For high-density marker data, rather than run scanone at both the markers and at a set of pseudomarkers, we reduce to just a set of evenly-spaced pseudomarkers

Usage

reduce2grid(cross)

Arguments

cross

An object of class cross. See read.cross for details.

Details

Genotype probabilities (from calc.genoprob) and/or imputations (from sim.geno) are subset to a grid of pseudomarkers.

This is so that, in the case of high-density markers, we can do the genome scan calculations at a smaller set of points (on an evenly-spaced grid, but not at the markers) to save computation time.

You need to first have run calc.genoprob and/or sim.geno, and you must use stepwidth="fixed".

When plotting results with plot.scanone, use incl.markers=FALSE, as the output of scanone won't include information about the marker locations and so will plot tick marks only at the first marker on each chromosome.

Value

The input cross object with included genotype probabilities or imputations subset to an evenly-spaced grid.

Author(s)

Karl W Broman, [email protected]

See Also

calc.genoprob, sim.geno, scanone, plot.scanone

Examples

data(hyper)
hyper <- calc.genoprob(hyper, step=2)
hypersub <- reduce2grid(hyper)

## Not run: out <- scanone(hypersub)
plot(out, incl.markers=FALSE)
## End(Not run)

Refine the positions of QTL

Description

Iteratively scan the positions for QTL in the context of a multiple QTL model, to try to identify the positions with maximum likelihood, for a fixed QTL model.

Usage

refineqtl(cross, pheno.col=1, qtl, chr, pos, qtl.name, covar=NULL, formula,
          method=c("imp","hk"), model=c("normal", "binary"), verbose=TRUE, maxit=10,
          incl.markers=TRUE, keeplodprofile=TRUE, tol=1e-4,
          maxit.fitqtl=1000, forceXcovar=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix to be used as the phenotype. One may also give a character string matching the phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

A QTL object, as produced by makeqtl, containing the positions of the QTL. Provide either qtl or the pair chr and pos.

chr

Vector indicating the chromosome for each QTL; if qtl is provided, this should not be.

pos

Vector indicating the positions for each QTL; if qtl is provided, this should not be.

qtl.name

Optional user-specified name for each QTL. If qtl is provided, this should not be.

covar

A matrix or data.frame of covariates. These must be strictly numeric.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are indicated as Q1, Q2, etc. Covariates are indicated by their names in covar.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

verbose

If TRUE, give feedback about progress. If verbose is an integer > 1, further messages from scanqtl are also displayed.

maxit

Maximum number of iterations.

incl.markers

If FALSE, do calculations only at points on an evenly spaced grid.

keeplodprofile

If TRUE, keep the LOD profiles from the last iteration as attributes to the output.

tol

Tolerance for convergence for the binary trait model.

maxit.fitqtl

Maximum number of iterations for fitting the binary trait model.

forceXcovar

If TRUE, force inclusion of X-chr-related covariates (like sex and cross direction).

Details

QTL positions are optimized, within the context of a fixed QTL model, by a scheme described in Zeng et al. (1999). Each QTL is considered one at a time (in a random order), and a scan is performed, allowing the QTL to vary across its chromosome, keeping the positions of all other QTL fixed. If there is another QTL on the chromosome, the position of the floating QTL is scanned from the end of the chromosome to the position of the flanking QTL. If the floating QTL is between two QTL on a chromosome, its position is scanned between those two QTL positions. Each QTL is moved to the position giving the highest likelihood, and the entire process is repeated until no further improvement in likelihood can be obtained.

One may provide either a qtl object (as produced by makeqtl), or vectors chr and pos (and, optionally, qtl.name) indicating the positions of the QTL.

If a qtl object is provided, QTL that do not appear in the model formula are ignored, but they remain part of the QTL object that is output.

Value

An object of class qtl, with QTL placed in their new positions.

If keeplodprofile=TRUE, LOD profiles from the last pass through the refinement algorithm are retained as an attribute, "lodprofile", to the object. These may be plotted with plotLodProfile.

Author(s)

Karl W Broman, [email protected]

References

Zeng, Z.-B., Kao, C.-H., and Basten, C. J. (1999) Estimating the genetic architecture of quantitative traits. Genet. Res. 74, 279–289.

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

fitqtl, makeqtl, scanqtl, addtoqtl, dropfromqtl, replaceqtl, plotLodProfile

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=2)
qtl <- makeqtl(fake.bc, chr=c(2,5), pos=c(32.5, 17.5), what="prob")
rqtl <- refineqtl(fake.bc, qtl=qtl, method="hk")

Reorder the QTL in a qtl object

Description

This function changes the order of the QTL in a QTL object.

Usage

reorderqtl(qtl, neworder)

Arguments

qtl

A qtl object, as created by makeqtl.

neworder

A vector containing the positive integers up to the number of QTL in qtl, indicating the new order for the QTL. If missing, the QTL are ordered by chromosome and then by their position within a chromosome.

Details

Everything in the input qtl is reordered except the altname component, which contains names of the form Q1, Q2, etc.

Value

The input qtl object, with the loci reordered.

Author(s)

Karl W Broman, [email protected]

See Also

makeqtl, fitqtl, dropfromqtl, addtoqtl, replaceqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 6, 13)
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

qtl <- reorderqtl(qtl, c(2,3,1))
qtl

qtl <- reorderqtl(qtl)
qtl

Replace the genetic map of a cross

Description

Replace the map portion of a cross object.

Usage

replace.map(cross, map)
## S3 method for class 'cross'
replacemap(object, map)

Arguments

cross

An object of class cross. See read.cross for details.

object

Same as cross.

map

A list containing the new genetic map. This must be the same length and with the same marker names as that contained in cross.

Value

The input cross object with the genetic map replaced by the input map. Maps for results from calc.genoprob, sim.geno and argmax.geno are also replaced, using interpolation if necessary.

Author(s)

Karl W Broman, [email protected]

See Also

pull.map, est.map

Examples

data(fake.f2)

newmap <- est.map(fake.f2)
plotMap(fake.f2, newmap)
fake.f2 <- replace.map(fake.f2, newmap)

Replace the genetic map in QTL mapping results with an alternate map

Description

Replace the positions of LOD scores in output from scanone with values based on an alternative map (such as a physical map), with pseudomarker locations determined by linear interpolation.

Usage

## S3 method for class 'scanone'
replacemap(object, map)

Arguments

object

An object of class "scanone", as output by the function scanone.

map

A list containing the alternative genetic map. All chromosomes in object should have corresponding chromosomes in map, and markers must be in the same order in the two maps. There must be at least two markers on each chromosome in map that appear in object.

Details

The positions of pseudomarkers are determined by linear interpolation between markers. In the case of pseudomarkers beyond the ends of the terminal markers on chromosomes, we use the overall lengths of the chromosome in object and map to determine the new spacing.

Value

The input object with the positions of LOD scores revised to match those in the input map.

Author(s)

Karl W Broman, [email protected]

See Also

replacemap.cross, est.map, replacemap.scantwo

Examples

data(fake.f2)

origmap <- pull.map(fake.f2)
newmap <- est.map(fake.f2)
fake.f2 <- replacemap(fake.f2, newmap)
fake.f2 <- calc.genoprob(fake.f2, step=2.5)
out <- scanone(fake.f2, method="hk")
out.rev <- replacemap(out, origmap)

Replace the genetic map in QTL mapping results with an alternate map

Description

Replace the positions of LOD scores in output from scantwo with values based on an alternative map (such as a physical map), with pseudomarker locations determined by linear interpolation.

Usage

## S3 method for class 'scantwo'
replacemap(object, map)

Arguments

object

An object of class "scantwo", as output by the function scantwo.

map

A list containing the alternative genetic map. All chromosomes in object should have corresponding chromosomes in map, and markers must be in the same order in the two maps. There must be at least two markers on each chromosome in map that appear in object.

Details

The positions of pseudomarkers are determined by linear interpolation between markers. In the case of pseudomarkers beyond the ends of the terminal markers on chromosomes, we use the overall lengths of the chromosome in object and map to determine the new spacing.

Value

The input object with the positions of LOD scores revised to match those in the input map.

Author(s)

Karl W Broman, [email protected]

See Also

replacemap.cross, est.map, replacemap.scanone

Examples

data(hyper)

origmap <- pull.map(hyper)
newmap <- est.map(hyper)
hyper <- replacemap(hyper, newmap)
hyper <- calc.genoprob(hyper, step=0)
out <- scantwo(hyper, method="hk")
out.rev <- replacemap(out, origmap)

Replace a QTL in a qtl object with a different position

Description

This function replaces a QTL or QTLs in a qtl object with a different position.

Usage

replaceqtl(cross, qtl, index, chr, pos, qtl.name, drop.lod.profile=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

qtl

A qtl object, as created by makeqtl.

index

Numeric index indicating the QTL to be replaced.

chr

Vector (of same length as index) indicating the chromosomes for the new QTL.

pos

Vector (of same length as index) indicating the positions for the new QTL. If there is no marker or pseudomarker at a position, the nearest position is used.

qtl.name

Optional vector (of same length as index) of user-specified names for each new QTL, used in the drop-one-term ANOVA table in fitqtl. If unspecified, the names will be of the form "Chr1@10" for a QTL on Chromsome 1 at 10 cM.

drop.lod.profile

If TRUE, remove any LOD profiles from the object.

Value

The input qtl object, but with some QTL replaced by new ones. See makeqtl for details on the format.

Author(s)

Karl W Broman, [email protected]

See Also

makeqtl, fitqtl, dropfromqtl, addtoqtl, reorderqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 6, 13)
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

qtl <- replaceqtl(fake.f2, qtl, 2, 6, 48.1)

Rescale genetic maps

Description

Rescale a genetic map by multiplying all positions by a constant

Usage

rescalemap(object, scale=1e-6)

Arguments

object

An object of class cross (see read.cross for details) or map (see sim.map for details).

scale

Scale factor by which all positions will be multiplied.

Details

This function is included particularly for the case that map positions in a cross object were provided in basepairs and one wishes to quickly convert them to Mbp or some other approximation of cM distances. (In the mouse, 1 cM is approximation 2 Mbp, so one might use scale=5e-7 in this function.)

Value

If the input is a map object, a map object is returned; if the input is a cross object, a cross object is returned. In either case, the positions of markers are simply multiplied by scale.

Author(s)

Karl W Broman, [email protected]

See Also

replace.map, est.map

Examples

data(hyper)
rescaled <- rescalemap(hyper, scale=2)
plotMap(hyper, rescaled)

Compare marker orders

Description

Investigate different marker orders for a given chromosome, comparing all possible permutations of a sliding window of markers.

Usage

ripple(cross, chr, window=4, method=c("countxo","likelihood"),
       error.prob=0.0001, map.function=c("haldane","kosambi","c-f","morgan"),
       maxit=4000, tol=1e-6, sex.sp=TRUE, verbose=TRUE, n.cluster=1)

Arguments

cross

An object of class cross. See read.cross for details.

chr

The chromosome to investigate. Only one chromosome is allowed. (This should be a character string referring to the chromosomes by name.)

window

Number of markers to include in the sliding window of permuted markers. Larger numbers result in the comparison of a greater number of marker orders, but will require a considerable increase in computation time.

method

Indicates whether to compare orders by counting the number of obligate crossovers, or by a likelihood analysis.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions.

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

verbose

If TRUE, information about the number of orders (and, if method="likelihood", about progress) are printed.

n.cluster

If the package snow is available and n.perm > 0, permutations are run in parallel using this number of nodes. This is really only useful with method="likelihood".

Details

For method="likelihood", calculations are done by first constructing a matrix of marker orders and then making repeated calls to the R function est.map. Of course, it would be faster to do everything within C, but this was a lot easier to code.

For method="countxo", calculations are done within C.

Value

A matrix, given class "ripple"; the first set of columns are marker indices describing the order. In the case of method="countxo", the last column is the number of obligate crossovers for each particular order. In the case of method="likelihood", the last two columns are LOD scores (log base 10 likelihood ratios) comparing each order to the initial order and the estimated chromosome length for the given order. Positive LOD scores indicate that the alternate order has more support than the original.

Author(s)

Karl W Broman, [email protected]

See Also

summary.ripple, switch.order, est.map, est.rf

Examples

data(badorder)
rip1 <- ripple(badorder, chr=1, window=3)
summary(rip1)

## Not run: 
rip2 <- ripple(badorder, chr=1, window=2, method="likelihood")
summary(rip2)

## End(Not run)

badorder <- switch.order(badorder, 1, rip1[2,])

Genome scan with a single QTL model

Description

Genome scan with a single QTL model, with possible allowance for covariates, using any of several possible models for the phenotype and any of several possible numerical methods.

Usage

scanone(cross, chr, pheno.col=1, model=c("normal","binary","2part","np"),
        method=c("em","imp","hk","ehk","mr","mr-imp","mr-argmax"),
        addcovar=NULL, intcovar=NULL, weights=NULL,
        use=c("all.obs", "complete.obs"), upper=FALSE,
        ties.random=FALSE, start=NULL, maxit=4000,
        tol=1e-4, n.perm, perm.Xsp=FALSE, perm.strata=NULL, verbose,
        batchsize=250, n.cluster=1, ind.noqtl)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes for which LOD scores should be calculated. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This can be a vector of integers; for methods "hk" and "imp" this can be considerably faster than doing them one at a time. One may also give a character strings matching the phenotype names. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

model

The phenotype model: the usual normal model, a model for binary traits, a two-part model or non-parametric analysis

method

Indicates whether to use the EM algorithm, imputation, Haley-Knott regression, the extended Haley-Knott method, or marker regression. Not all methods are available for all models. Marker regression is performed either by dropping individuals with missing genotypes ("mr"), or by first filling in missing data using a single imputation ("mr-imp") or by the Viterbi algorithm ("mr-argmax").

addcovar

Additive covariates; allowed only for the normal and binary models.

intcovar

Interactive covariates (interact with QTL genotype); allowed only for the normal and binary models.

weights

Optional weights of individuals. Should be either NULL or a vector of length n.ind containing positive weights. Used only in the case model="normal".

use

In the case that multiple phenotypes are selected to be scanned, this argument indicates whether to use all individuals, including those missing some phenotypes, or just those individuals that have data on all selected phenotypes.

upper

Used only for the two-part model; if true, the "undefined" phenotype is the maximum observed phenotype; otherwise, it is the smallest observed phenotype.

ties.random

Used only for the non-parametric "model"; if TRUE, ties in the phenotypes are ranked at random. If FALSE, average ranks are used and a corrected LOD score is calculated.

start

Used only for the EM algorithm with the normal model and no covariates. If NULL, use the usual starting values; if length 1, use random initial weights for EM; otherwise, this should be a vector of length n+1 (where n is the number of possible genotypes for the cross), giving the initial values for EM.

maxit

Maximum number of iterations for methods "em" and "ehk".

tol

Tolerance value for determining convergence for methods "em" and "ehk".

n.perm

If specified, a permutation test is performed rather than an analysis of the observed data. This argument defines the number of permutation replicates.

perm.Xsp

If n.perm > 0, so that a permutation test will be performed, this indicates whether separate permutations should be performed for the autosomes and the X chromosome, in order to get an X-chromosome-specific LOD threshold. In this case, additional permutations are performed for the X chromosome.

perm.strata

If n.perm > 0, this may be used to perform a stratified permutation test. This should be a vector with the same number of individuals as in the cross data. Unique values indicate the individual strata, and permutations will be performed within the strata.

verbose

In the case n.perm is specified, display information about the progress of the permutation tests.

batchsize

The number of phenotypes (or permutations) to be run as a batch; used only for methods "hk" and "imp".

n.cluster

If the package snow is available and n.perm > 0, permutations are run in parallel using this number of nodes.

ind.noqtl

Indicates individuals who should not be allowed a QTL effect (used rarely, if at all); this is a logical vector of same length as there are individuals in the cross.

Details

Use of the EM algorithm, Haley-Knott regression, and the extended Haley-Knott method require that multipoint genotype probabilities are first calculated using calc.genoprob. The imputation method uses the results of sim.geno.

Individuals with missing phenotypes are dropped.

In the case that n.perm>0, so that a permutation test is performed, the R function scanone is called repeatedly. If perm.Xsp=TRUE, separate permutations are performed for the autosomes and the X chromosome, so that an X-chromosome-specific threshold may be calculated. In this case, n.perm specifies the number of permutations used for the autosomes; for the X chromosome, n.perm ×LA/LX\times \, L_A/L_X permutations will be run, where LAL_A and LXL_X are the total genetic lengths of the autosomes and X chromosome, respectively. More permutations are needed for the X chromosome in order to obtain thresholds of similar accuracy.

For further details on the models, the methods and the use of covariates, see below.

Value

If n.perm is missing, the function returns a data.frame whose first two columns contain the chromosome IDs and cM positions. Subsequent columns contain the LOD scores for each phenotype. In the case of the two-part model, there are three LOD score columns for each phenotype: LOD(p,μp,\mu), LOD(pp) and LOD(μ\mu). The result is given class "scanone" and has attributes "model", "method", and "type" (the latter is the type of cross analyzed).

If n.perm is specified, the function returns the results of a permutation test and the output has class "scanoneperm". If perm.Xsp=FALSE, the function returns a matrix with n.perm rows, each row containing the genome-wide maximum LOD score for each of the phenotypes. In the case of the two-part model, there are three columns for each phenotype, corresponding to the three different LOD scores. If perm.Xsp=TRUE, the result contains separate permutation results for the autosomes and the X chromosome respectively, and an attribute indicates the lengths of the chromosomes and an indicator of which chromosome is X.

Models

The normal model is the standard model for QTL mapping (see Lander and Botstein 1989). The residual phenotypic variation is assumed to follow a normal distribution, and analysis is analogous to analysis of variance.

The binary model is for the case of a binary phenotype, which must have values 0 and 1. The proportions of 1's in the different genotype groups are compared. Currently only methods em, hk, and mr are available for this model. See Xu and Atchley (1996) and Broman (2003).

The two-part model is appropriate for the case of a spike in the phenotype distribution (for example, metastatic density when many individuals show no metastasis, or survival time following an infection when individuals may recover from the infection and fail to die). The two-part model was described by Boyartchuk et al. (2001) and Broman (2003). Individuals with QTL genotype gg have probability pgp_g of having an undefined phenotype (the spike), while if their phenotype is defined, it comes from a normal distribution with mean μg\mu_g and common standard deviation σ\sigma. Three LOD scores are calculated: LOD(p,μp,\mu) is for the test of the hypothesis that pg=pp_g = p and μg=μ\mu_g = \mu. LOD(pp) is for the test that pg=pp_g = p while the μg\mu_g may vary. LOD(μ\mu) is for the test that μg=μ\mu_g = \mu while the pgp_g may vary.

With the non-parametric "model", an extension of the Kruskal-Wallis test is used; this is similar to the method described by Kruglyak and Lander (1995). In the case of incomplete genotype information (such as at locations between genetic markers), the Kruskal-Wallis statistic is modified so that the rank for each individual is weighted by the genotype probabilities, analogous to Haley-Knott regression. For this method, if the argument ties.random is TRUE, ties in the phenotypes are assigned random ranks; if it is FALSE, average ranks are used and a corrected LOD score is calculate. Currently the method argument is ignored for this model.

Methods

em: maximum likelihood is performed via the EM algorithm (Dempster et al. 1977), first used in this context by Lander and Botstein (1989).

imp: multiple imputation is used, as described by Sen and Churchill (2001).

hk: Haley-Knott regression is used (regression of the phenotypes on the multipoint QTL genotype probabilities), as described by Haley and Knott (1992).

ehk: the extended Haley-Knott method is used (like H-K, but taking account of the variances), as described in Feenstra et al. (2006).

mr: Marker regression is used. Analysis is performed only at the genetic markers, and individuals with missing genotypes are discarded. See Soller et al. (1976).

Covariates

Covariates are allowed only for the normal and binary models. The normal model is y=βq+Aγ+Zδq+ϵy = \beta_q + A \gamma + Z \delta_q + \epsilon where q is the unknown QTL genotype, A is a matrix of additive covariates, and Z is a matrix of covariates that interact with the QTL genotype. The columns of Z are forced to be contained in the matrix A. The binary model is the logistic regression analog.

The LOD score is calculated comparing the likelihood of the above model to that of the null model y=μ+Aγ+ϵy = \mu + A \gamma + \epsilon.

Covariates must be numeric matrices. Individuals with any missing covariates are discarded.

X chromosome

The X chromosome must be treated specially in QTL mapping. See Broman et al. (2006).

If both males and females are included, male hemizygotes are allowed to be different from female homozygotes. Thus, in a backcross, we will fit separate means for the genotype classes AA, AB, AY, and BY. In such cases, sex differences in the phenotype could cause spurious linkage to the X chromosome, and so the null hypothesis must be changed to allow for a sex difference in the phenotype.

Numerous special cases must be considered, as detailed in the following table.

BC Sexes Null Alternative df
both sexes sex AA/AB/AY/BY 2
all female grand mean AA/AB 1
all male grand mean AY/BY 1
F2 Direction Sexes Null Alternative df
Both both sexes femaleF/femaleR/male AA/ABf/ABr/BB/AY/BY 3
all female pgm AA/ABf/ABr/BB 2
all male grand mean AY/BY 1
Forward both sexes sex AA/AB/AY/BY 2
all female grand mean AA/AB 1
all male grand mean AY/BY 1
Backward both sexes sex AB/BB/AY/BY 2
all female grand mean AB/BB 1
all male grand mean AY/BY 1

In the case that the number of degrees of freedom for the linkage test for the X chromosome is different from that for autosomes, a separate X-chromosome LOD threshold is recommended. Autosome- and X-chromosome-specific LOD thresholds may be estimated by permutation tests with scanone by setting n.perm>0 and using perm.Xsp=TRUE.

Author(s)

Karl W Broman, [email protected]; Hao Wu

References

Boyartchuk, V. L., Broman, K. W., Mosher, R. E., D'Orazio S. E. F., Starnbach, M. N. and Dietrich, W. F. (2001) Multigenic control of Listeria monocytogenes susceptibility in mice. Nature Genetics 27, 259–260.

Broman, K. W. (2003) Mapping quantitative trait loci in the case of a spike in the phenotype distribution. Genetics 163, 1169–1175.

Broman, K. W., Sen, Ś, Owens, S. E., Manichaikul, A., Southard-Smith, E. M. and Churchill G. A. (2006) The X chromosome in quantitative trait locus mapping. Genetics, 174, 2151–2158.

Churchill, G. A. and Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

Dempster, A. P., Laird, N. M. and Rubin, D. B. (1977) Maximum likelihood from incomplete data via the EM algorithm. J. Roy. Statist. Soc. B, 39, 1–38.

Feenstra, B., Skovgaard, I. M. and Broman, K. W. (2006) Mapping quantitative trait loci by an extension of the Haley-Knott regression method using estimating equations. Genetics, 173, 2111–2119.

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Kruglyak, L. and Lander, E. S. (1995) A nonparametric approach for mapping quantitative trait loci. Genetics 139, 1421–1428.

Lander, E. S. and Botstein, D. (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

Soller, M., Brody, T. and Genizi, A. (1976) On the power of experimental designs for the detection of linkage between marker loci and quantitative loci in crosses between inbred lines. Theor. Appl. Genet. 47, 35–39.

Xu, S., and Atchley, W.R. (1996) Mapping quantitative trait loci for complex binary diseases using line crosses. Genetics 143, 1417–1424.

See Also

plot.scanone, summary.scanone, scantwo, calc.genoprob, sim.geno, max.scanone, summary.scanoneperm, -.scanone, +.scanone

Examples

###################
# Normal Model
###################
data(hyper)

# Genotype probabilities for EM and H-K
## Not run: hyper <- calc.genoprob(hyper, step=2.5)

out.em <- scanone(hyper, method="em")
out.hk <- scanone(hyper, method="hk")

# Summarize results: peaks above 3
summary(out.em, thr=3)
summary(out.hk, thr=3)

# An alternate method of summarizing:
#     patch them together and then summarize
out <- c(out.em, out.hk)
summary(out, thr=3, format="allpeaks")

# Plot the results
plot(out.hk, out.em)
plot(out.hk, out.em, chr=c(1,4), lty=1, col=c("blue","black"))

# Imputation; first need to run sim.geno
# Do just chromosomes 1 and 4, to save time
## Not run: hyper.c1n4 <- sim.geno(subset(hyper, chr=c(1,4)),
                       step=2.5, n.draws=8)

## End(Not run)
out.imp <- scanone(hyper.c1n4, method="imp")
summary(out.imp, thr=3)

# Plot all three results
plot(out.imp, out.hk, out.em, chr=c(1,4), lty=1,
     col=c("red","blue","black"))

# extended Haley-Knott
out.ehk <- scanone(hyper, method="ehk")
plot(out.hk, out.em, out.ehk, chr=c(1,4))

# Permutation tests
## Not run: permo <- scanone(hyper, method="hk", n.perm=1000)


# Threshold from the permutation test
summary(permo, alpha=c(0.05, 0.10))

# Results above the 0.05 threshold
summary(out.hk, perms=permo, alpha=0.05)


####################
# scan with square-root of phenotype
#   (Note that pheno.col can be a vector of phenotype values)
####################
out.sqrt <- scanone(hyper, pheno.col=sqrt(pull.pheno(hyper, 1)))
plot(out.em - out.sqrt, ylim=c(-0.1,0.1),
     ylab="Difference in LOD")
abline(h=0, lty=2, col="gray")


####################
# Stratified permutations
####################
extremes <- (nmissing(hyper)/totmar(hyper) < 0.5)

## Not run: operm.strat <- scanone(hyper, method="hk", n.perm=1000,
                       perm.strata=extremes)

## End(Not run)

summary(operm.strat)



####################
# X-specific permutations
####################
data(fake.f2)

## Not run: fake.f2 <- calc.genoprob(fake.f2, step=2.5)


# genome scan
out <- scanone(fake.f2, method="hk")

# X-chr-specific permutations
## Not run: operm <- scanone(fake.f2, method="hk", n.perm=1000, perm.Xsp=TRUE)


# thresholds
summary(operm)

# scanone summary with p-values
summary(out, perms=operm, alpha=0.05, pvalues=TRUE)



###################
# Non-parametric
###################
out.np <- scanone(hyper, model="np")
summary(out.np, thr=3)

# Plot with previous results
plot(out.np, chr=c(1,4), lty=1, col="green")
plot(out.imp, out.hk, out.em, chr=c(1,4), lty=1,
     col=c("red","blue","black"), add=TRUE)

###################
# Two-part Model
###################
data(listeria)

## Not run: listeria <- calc.genoprob(listeria,step=2.5)

out.2p <- scanone(listeria, model="2part", upper=TRUE)
summary(out.2p, thr=c(5,3,3), format="allpeaks")

# Plot all three LOD scores together
plot(out.2p, out.2p, out.2p, lodcolumn=c(2,3,1), lty=1, chr=c(1,5,13),
     col=c("red","blue","black"))

# Permutation test
## Not run: permo <- scanone(listeria, model="2part", upper=TRUE,
                 n.perm=1000)

## End(Not run)

# Thresholds
summary(permo)

###################
# Binary model
###################
binphe <- as.numeric(pull.pheno(listeria,1)==264)
out.bin <- scanone(listeria, pheno.col=binphe, model="binary")
summary(out.bin, thr=3)

# Plot LOD for binary model with LOD(p) from 2-part model
plot(out.bin, out.2p, lodcolumn=c(1,2), lty=1, col=c("black", "red"),
     chr=c(1,5,13))

# Permutation test
## Not run: permo <- scanone(listeria, pheno.col=binphe, model="binary",
                 n.perm=1000)

## End(Not run)

# Thresholds
summary(permo)

###################
# Covariates
###################
data(fake.bc)

## Not run: fake.bc <- calc.genoprob(fake.bc, step=2.5)


# genome scans without covariates
out.nocovar <- scanone(fake.bc)

# genome scans with covariates
ac <- pull.pheno(fake.bc, c("sex","age"))
ic <- pull.pheno(fake.bc, "sex")

out.covar <- scanone(fake.bc, pheno.col=1,
                     addcovar=ac, intcovar=ic)
summary(out.nocovar, thr=3)
summary(out.covar, thr=3)
plot(out.covar, out.nocovar, chr=c(2,5,10))

Bootstrap to get interval estimate of QTL location

Description

Nonparametric bootstrap to get an estimated confidence interval for the location of a QTL, in the context of a single-QTL model.

Usage

scanoneboot(cross, chr, pheno.col=1, model=c("normal","binary","2part","np"),
            method=c("em","imp","hk","ehk","mr","mr-imp","mr-argmax"),
            addcovar=NULL, intcovar=NULL, weights=NULL,
            use=c("all.obs", "complete.obs"), upper=FALSE,
            ties.random=FALSE, start=NULL, maxit=4000,
            tol=1e-4, n.boot=1000, verbose=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

The chromosome to investigate. Only one chromosome is allowed. (This should be a character string referring to the chromosomes by name.)

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

model

The phenotypic model: the usual normal model, a model for binary traits, a two-part model or non-parametric analysis

method

Indicates whether to use the EM algorithm, imputation, Haley-Knott regression, the extended Haley-Knott method, or marker regression. Not all methods are available for all models. Marker regression is performed either by dropping individuals with missing genotypes ("mr"), or by first filling in missing data using a single imputation ("mr-imp") or by the Viterbi algorithm ("mr-argmax").

addcovar

Additive covariates; allowed only for the normal and binary models.

intcovar

Interactive covariates (interact with QTL genotype); allowed only for the normal and binary models.

weights

Optional weights of individuals. Should be either NULL or a vector of length n.ind containing positive weights. Used only in the case model="normal".

use

In the case that multiple phenotypes are selected to be scanned, this argument indicates whether to use all individuals, including those missing some phenotypes, or just those individuals that have data on all selected phenotypes.

upper

Used only for the two-part model; if true, the "undefined" phenotype is the maximum observed phenotype; otherwise, it is the smallest observed phenotype.

ties.random

Used only for the non-parametric "model"; if TRUE, ties in the phenotypes are ranked at random. If FALSE, average ranks are used and a corrected LOD score is calculated.

start

Used only for the EM algorithm with the normal model and no covariates. If NULL, use the usual starting values; if length 1, use random initial weights for EM; otherwise, this should be a vector of length n+1 (where n is the number of possible genotypes for the cross), giving the initial values for EM.

maxit

Maximum number of iterations for methods "em" and "ehk".

tol

Tolerance value for determining convergence for methods "em" and "ehk".

n.boot

Number of bootstrap replicates.

verbose

If TRUE, display information about the progress of the bootstrap.

Details

We recommend against the use of the bootstrap to derive a confidence interval for the location of a QTL; see Manichaikul et al. (2006). Use lodint or bayesint instead.

The bulk of the arguments are the same as for the scanone function. A single chromosome should be indicated with the chr argument; otherwise, we focus on the first chromosome in the input cross object.

A single-dimensional scan on the relevant chromosome is performed. We further perform a nonparametric bootstrap (sampling individuals with replacement from the available data, to create a new data set with the same size as the input cross; some individuals with be duplicated and some omitted). The same scan is performed with the resampled data; for each bootstrap replicate, we store only the location with maximum LOD score.

Use summary.scanoneboot to obtain the desired confidence interval.

Value

A vector of length n.boot, giving the estimated QTL locations in the bootstrap replicates. The results for the original data are included as an attribute, "results".

Author(s)

Karl W Broman, [email protected]

References

Manichaikul, A., Dupuis, J., Sen, Ś and Broman, K. W. (2006) Poor performance of bootstrap confidence intervals for the location of a quantitative trait locus. Genetics 174, 481–489.

Visscher, P. M., Thompson, R. and Haley, C. S. (1996) Confidence intervals in QTL mapping by bootstrap. Genetics 143, 1013–1020.

See Also

scanone, summary.scanoneboot, plot.scanoneboot, lodint, bayesint

Examples

data(fake.f2)
fake.f2 <- calc.genoprob(fake.f2, step=1, err=0.001)
## Not run: bootoutput <- scanoneboot(fake.f2, chr=13, method="hk")


plot(bootoutput)
summary(bootoutput)

Genome scan for QTL affecting mean and/or variance

Description

Genome scan with a single QTL model for loci that can affect the variance as well as the mean.

Usage

scanonevar(cross, pheno.col=1, mean_covar=NULL, var_covar=NULL,
           maxit=25, tol=1e-6, quiet=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This must be a single value (integer index or phenotype name) or a numeric vector of phenotype values, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

mean_covar

Numeric matrix with covariates affecting the mean.

var_covar

Numeric matrix with covariates affecting the variances.

maxit

Maximum number of iterations in the algorithm to fit the model at a given position.

tol

Tolerance for convergence.

quiet

If FALSE, print some information about the course of the calculations.

Value

A data frame (with class "scanone", in the form output by scanone), with four columns: chromosome, position, the -log P-value for the mean effect, and the -log P-value for the effect on the variance. The result is given class "scanone"

Author(s)

Lars Ronnegard and Karl Broman

References

Ronnegard, L. and Valdar W. (2011) Detecting major genetic loci controlling phenotypic variability in experimental crosses. Genetics 188:435-447

Ronnegard, L. and Valdar W. (2012) Recent developments in statistical methods for detecting genetic loci affecting phenotypic variability. BMC Genetics 13:63

See Also

scanone, summary.scanone, calc.genoprob, summary.scanoneperm

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=2.5)
out <- scanonevar(fake.bc)
color <- c("slateblue", "violetred")
plot(out, lod=1:2, col=color, bandcol="gray80")
legend("topright", lwd=2, c("mean", "variance"), col=color)

# use format="allpeaks" to get summary for each of mean and variance
#  also consider format="tabByCol" or format="tabByChr"
summary(out, format="allpeaks")

# with sex and age as covariates
covar <- fake.bc$pheno[,c("sex", "age")]
out.cov <- scanonevar(fake.bc, mean_covar=covar, var_covar=covar)

Permutation test for mean effect in scanonevar

Description

Executes permutations of the genotypes in the mean-effect part of scanonevar

Usage

scanonevar.meanperm(cross, pheno.col=1, mean_covar=NULL, var_covar=NULL,
           maxit=25, tol=1e-6, n.mean.perm = 2, seed = 27517, quiet=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This must be a single value (integer index or phenotype name) or a numeric vector of phenotype values, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

mean_covar

Numeric matrix with covariates affecting the mean.

var_covar

Numeric matrix with covariates affecting the variances.

maxit

Maximum number of iterations in the algorithm to fit the model at a given position.

tol

Tolerance for convergence.

n.mean.perm

Numeric vector of length one indicates the number of permutations to execute.

seed

Numeric vector of length one indicates the random seed to start the permutations.

quiet

If FALSE, print some information about the course of the calculations.

Value

A vector of length n.mean.perm of the maximum negative log10 p-value that resulted from each permutation.


Permutation test for variance effect in scanonevar

Description

Executes permutations of the genotypes in the variance-effect part of scanonevar

Usage

scanonevar.varperm(cross, pheno.col=1, mean_covar=NULL, var_covar=NULL,
                   maxit=25, tol=1e-6, n.var.perm = 2, seed = 27517, quiet=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This must be a single value (integer index or phenotype name) or a numeric vector of phenotype values, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

mean_covar

Numeric matrix with covariates affecting the mean.

var_covar

Numeric matrix with covariates affecting the variances.

maxit

Maximum number of iterations in the algorithm to fit the model at a given position.

tol

Tolerance for convergence.

n.var.perm

Numeric vector of length one indicates the number of permutations to execute.

seed

Numeric vector of length one indicates the random seed to start the permutations.

quiet

If FALSE, print some information about the course of the calculations.

Value

A vector of length n.var.perm of the maximum negative log10 p-value that resulted from each permutation.


Single-QTL genome scan to map QTL to a phylogenetic tree

Description

Jointly consider multiple intercrosses with a single diallelic QTL model, considering all possible partitions of the strains into the two QTL allele groups.

Usage

scanPhyloQTL(crosses, partitions, chr, pheno.col=1,
             model=c("normal", "binary"), method=c("em", "imp", "hk"),
             addcovar, maxit=4000, tol=0.0001, useAllCrosses=TRUE,
             verbose=FALSE)

Arguments

crosses

A list with each component being an intercross, as an object of class cross (see read.cross for details). The names (of the form "AB") indicate the strains in the cross.

partitions

A vector of character strings of the form "AB|CD" or "A|BCD" indicating the set of paritions of the strains into two allele groups. If missing, all partitions should be considered.

chr

Optional vector indicating the chromosomes for which LOD scores should be calculated. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This can be a vector of integers; for methods "hk" and "imp" this can be considerably faster than doing them one at a time. One may also give a character strings matching the phenotype names. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

model

The phenotype model: the usual normal model or a model for binary traits

method

Indicates whether to use the EM algorithm, imputation, or Haley-Knott regression.

addcovar

Optional set of additive covariates to include in the analysis, as a list with the same length as crosses. They must be numeric vectors or matrices, as for scanone.

maxit

Maximum number of iterations for method "em".

tol

Tolerance value for determining convergence for method "em".

useAllCrosses

If TRUE, use all crosses in the analysis of all partitions, with crosses not segregating the QTL included in the estimation of the residual variance.

verbose

If TRUE, print information about progress.

Details

The aim is to jointly consider multiple intercrosses to not just map QTL but to also, under the assumption of a single diallelic QTL, identify the set of strains with each QTL allele.

For each partition (of the strains into two groups) that is under consideration, we pull out the set of crosses that are segregating the QTL, re-code the alleles, and combine the crosses into one large cross. Crosses not segregating the QTL are also used, though with no QTL effects.

Additive covariate indicators for the crosses are included in the analysis, to allow for the possibility that there are overall shifts in the phenotypes between crosses.

Value

A data frame, as for the output of scanone, though with LOD score columns for each partition that is considered. The result is given class "scanPhyloQTL".

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Kim, S., An\'e, C. and Payseur, B. A. Mapping quantitative trait loci to a phylogenetic tree. In preparation.

See Also

plot.scanPhyloQTL, summary.scanPhyloQTL, max.scanPhyloQTL, inferredpartitions, simPhyloQTL

Examples

# example map; drop X chromosome
data(map10)
map10 <- map10[1:19]


# simulate data
x <- simPhyloQTL(4, partition="AB|CD", crosses=c("AB", "AC", "AD"),
                 map=map10, n.ind=150,
                 model=c(1, 50, 0.5, 0))

# run calc.genoprob on each cross
## Not run: x <- lapply(x, calc.genoprob, step=2)


# scan genome, at each position trying all possible partitions
out <- scanPhyloQTL(x, method="hk")

# maximum peak
max(out, format="lod")

# approximate posterior probabilities at peak
max(out, format="postprob")

# all peaks above a threshold for LOD(best) - LOD(2nd best)
summary(out, threshold=1, format="lod")

# all peaks above a threshold for LOD(best), showing approx post'r prob
summary(out, format="postprob", threshold=3)

# plot results
plot(out)

General QTL scan

Description

Performs a multiple QTL scan for specified chromosomes and positions or intervals, with the possible inclusion of QTL-QTL interactions and/or covariates.

Usage

scanqtl(cross, pheno.col=1, chr, pos, covar=NULL, formula,
        method=c("imp","hk"), model=c("normal", "binary"),
        incl.markers=FALSE, verbose=TRUE, tol=1e-4, maxit=1000,
        forceXcovar=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

Column number in the phenotype matrix to be used as the phenotype. One may also give a character string matching a phenotype name. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

chr

Vector indicating the chromosome for each QTL. (These should be character strings referring to the chromosomes by name.)

pos

List indicating the positions or intervals on the chromosome to be scanned. Each element should be either a single number (for a specific position) or a pair of numbers (for an interval).

covar

A matrix or data.frame of covariates. These must be strictly numeric.

formula

An object of class formula indicating the model to be fitted. (It can also be the character string representation of a formula.) QTLs are indicated as Q1, Q2, etc. Covariates are indicated by their names in covar.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

incl.markers

If FALSE, do calculations only at points on an evenly spaced grid. If calc.genoprob or sim.geno were run with stepwidth="variable" or stepwidth="max", we force incl.markers=TRUE.

verbose

If TRUE, give feedback about progress.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

forceXcovar

If TRUE, force inclusion of X-chr-related covariates (like sex and cross direction).

Details

The formula is used to specified the model to be fit. In the formula, use Q1, Q2, etc., or q1, q2, etc., to represent the QTLs, and the column names in the covariate data frame to represent the covariates.

We enforce a hierarchical structure on the model formula: if a QTL or covariate is in involved in an interaction, its main effect are also be included.

Only the interaction terms need to be specifed in the formula. The main effects of all input QTLs (as specified by chr and pos) and covariates (as specifed by covar) will be included by default. For example, if the formula is y~Q1*Q2*Sex, and there are three elements in input chr and pos and Sex is one of the column names for input covariates, the formula used in genome scan will be y ~ Q1 + Q2 + Q3 + Sex + Q1:Q2 + Q1:Sex + Q2:Sex + Q1:Q2:Sex.

The input pos is a list or vector to specify the position/range of the input chromosomes to be scanned. If it is a vector, it gives the precise positions of the QTL on the chromosomes. If it is a list, it will contain either the precise positions or a range on the chromosomes. For example, consider the case that the input chr = c(1, 6, 13). If pos = c(9.8, 34.0, 18.6), it means to fit a model with QTL on chromosome 1 at 9.8cM, chromosome 6 at 34cM and chromosome 13 at 18.6cM. If pos = list(c(5,15), c(30,36), 18), it means to scan chromosome 1 from 5cM to 15cM, chromosome 6 from 30cM to 36cM, fix the QTL on chromosome 13 at 18cM.

Value

An object of class scanqtl. It is a multi-dimensional array of LOD scores, with the number of dimension equal to the number of QTLs specifed.

Author(s)

Hao Wu

References

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

See Also

fitqtl, makeqtl, refineqtl

Examples

data(fake.f2)

# take out several QTLs
qc <- c(1, 8, 13)
fake.f2 <- subset(fake.f2, chr=qc)

# imputate genotypes

fake.f2 <- calc.genoprob(fake.f2, step=5, err=0.001)

# 2-dimensional genome scan with additive 3-QTL model
pos <- list(c(15,35), c(45,65), 28)
result <- scanqtl(fake.f2, pheno.col=1, chr=qc, pos=pos,
                  formula=y~Q1+Q2+Q3, method="hk")

# image of the results
# chr locations
chr1 <- as.numeric(matrix(unlist(strsplit(colnames(result),"@")),
                   ncol=2,byrow=TRUE)[,2])
chr8 <- as.numeric(matrix(unlist(strsplit(rownames(result),"@")),
                   ncol=2,byrow=TRUE)[,2])
# image plot
image(chr1, chr8, t(result), las=1, col=rev(rainbow(256,start=0,end=2/3)))

# do the same, allowing the QTLs on chr 1 and 13 to interact
result2 <- scanqtl(fake.f2, pheno.col=1, chr=qc, pos=pos,
                   formula=y~Q1+Q2+Q3+Q1:Q3, method="hk")
# image plot
image(chr1, chr8, t(result2), las=1, col=rev(rainbow(256,start=0,end=2/3)))

Two-dimensional genome scan with a two-QTL model

Description

Perform a two-dimensional genome scan with a two-QTL model, with possible allowance for covariates.

Usage

scantwo(cross, chr, pheno.col=1, model=c("normal","binary"),
        method=c("em","imp","hk","mr","mr-imp","mr-argmax"),
        addcovar=NULL, intcovar=NULL, weights=NULL,
        use=c("all.obs", "complete.obs"),
        incl.markers=FALSE, clean.output=FALSE,
        clean.nmar=1, clean.distance=0,
        maxit=4000, tol=1e-4,
        verbose=TRUE, n.perm, perm.Xsp=FALSE, perm.strata=NULL,
        assumeCondIndep=FALSE, batchsize=250, n.cluster=1)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes for which LOD scores should be calculated. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This can be a vector of integers; for methods "hk" and "imp" this can be considerably faster than doing them one at a time. One may also give character strings matching the phenotype names. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

model

The phenotype model: the usual normal model or a model for binary traits.

method

Indicates whether to use the the EM algorithm, imputation, Haley-Knott regression, or marker regression. Marker regression is performed either by dropping individuals with missing genotypes ("mr"), or by first filling in missing data using a single imputation ("mr-imp") or by the Viterbi algorithm ("mr-argmax").

addcovar

Additive covariates.

intcovar

Interactive covariates (interact with QTL genotype).

weights

Optional weights of individuals. Should be either NULL or a vector of length n.ind containing positive weights. Used only in the case model="normal".

use

In the case that multiple phenotypes are selected to be scanned, this argument indicates whether to use all individuals, including those missing some phenotypes, or just those individuals that have data on all selected phenotypes.

incl.markers

If FALSE, do calculations only at points on an evenly spaced grid. If calc.genoprob or sim.geno were run with stepwidth="variable" or stepwidth="max", we force incl.markers=TRUE.

clean.output

If TRUE, clean the output with clean.scantwo, replacing LOD scores for pairs of positions that are not well separated with 0. In permutations, this will be done for each permutation replicate. This can be important for the case of method="em", as there can be difficulty with algorithm convergence in these regions.

clean.nmar

If clean.output=TRUE, this is the number of markers that must separate two positions.

clean.distance

If clean.output=TRUE, this is the cM distance that must separate two positions.

maxit

Maximum number of iterations; used only with method "em".

tol

Tolerance value for determining convergence; used only with method "em".

verbose

If TRUE, display information about the progress of calculations. For method "em", if verbose is an integer above 1, further details on the progress of the algorithm will be displayed.

n.perm

If specified, a permutation test is performed rather than an analysis of the observed data. This argument defines the number of permutation replicates.

perm.Xsp

If n.perm > 0, so that a permutation test will be performed, this indicates whether separate permutations should be performed for the autosomes and the X chromosome, in order to get an X-chromosome-specific LOD threshold. In this case, additional permutations are performed for the X chromosome.

perm.strata

If n.perm > 0, this may be used to perform a stratified permutation test. This should be a vector with the same number of individuals as in the cross data. Unique values indicate the individual strata, and permutations will be performed within the strata.

assumeCondIndep

If TRUE, assume conditional independence of QTL genotypes given marker genotypes. This is an approximation, but it may speed things up.

batchsize

The number of phenotypes (or permutations) to be run as a batch; used only for methods "hk" and "imp".

n.cluster

If the package snow is available and n.perm > 0, permutations are run in parallel using this number of nodes.

Details

Standard interval mapping (method="em") and Haley-Knott regression (method="hk") require that multipoint genotype probabilities are first calculated using calc.genoprob. The imputation method uses the results of sim.geno.

The method "em" is standard interval mapping by the EM algorithm (Dempster et al. 1977; Lander and Botstein 1989). Marker regression (method="mr") is simply linear regression of phenotypes on marker genotypes (individuals with missing genotypes are discarded). Haley-Knott regression (method="hk") uses the regression of phenotypes on multipoint genotype probabilities. The imputation method (method="imp") uses the pseudomarker algorithm described by Sen and Churchill (2001).

Individuals with missing phenotypes are dropped.

In the presence of covariates, the full model is

y=μ+βq1+βq2+βq1×q2+Aγ+Zδq1+Zδq2+Zδq1×q2+ϵy = \mu + \beta_{q_1} + \beta_{q_2} + \beta_{q_1 \times q_2} + A \gamma + Z \delta_{q_1} + Z \delta_{q_2} + Z \delta_{q_1 \times q_2} + \epsilon

where q1q_1 and q2q_2 are the unknown QTL genotypes at two locations, A is a matrix of covariates, and Z is a matrix of covariates that interact with QTL genotypes. The columns of Z are forced to be contained in the matrix A.

The above full model is compared to the additive QTL model,

y=μ+βq1+βq2+Aγ+Zδq1+Zδq2+ϵy = \mu + \beta_{q_1} + \beta_{q_2} + A \gamma + Z \delta_{q_1} + Z \delta_{q_2} + \epsilon

and also to the null model, with no QTL,

y=μ+Aγ+ϵy = \mu + A \gamma + \epsilon

In the case that n.perm is specified, the R function scantwo is called repeatedly.

For model="binary", a logistic regression model is used.

Value

If n.perm is missing, the function returns a list with class "scantwo" and containing three components. The first component is a matrix of dimension [tot.pos x tot.pos]; the upper triangle contains the LOD scores for the additive model, and the lower triangle contains the LOD scores for the full model. The diagonal contains the results of scanone. The second component of the output is a data.frame indicating the locations at which the two-QTL LOD scores were calculated. The first column is the chromosome identifier, the second column is the position in cM, the third column is a 1/0 indicator for ease in later pulling out only the equally spaced positions, and the fourth column indicates whether the position is on the X chromosome or not. The final component is a version of the results of scanone including sex and/or cross direction as additive covariates, which is needed for a proper calculation of conditional LOD scores.

If n.perm is specified, the function returns a list with six different LOD scores from each of the permutation replicates. First, the maximum LOD score for the full model (two QTLs plus an interaction). Second, for each pair of chromosomes, we take the difference between the full LOD and the maximum single-QTL LOD for those two chromosomes, and then maximize this across chromosome pairs. Third, for each pair of chromosomes we take the difference between the maximum full LOD and the maximum additive LOD, and then maximize this across chromosome pairs. Fourth, the maximum LOD score for the additive QTL model. Fifth, for each pair of chromosomes, we take the difference between the additive LOD and the maximum single-QTL LOD for those two chromosomes, and then maximize this across chromosome pairs. Finally, the maximum single-QTL LOD score (that is, from a single-QTL scan). The latter is not used in summary.scantwo, but does get calculated at each permutation, so we include it for the sake of completeness.

If n.perm is specified and perm.Xsp=TRUE, the result is a list with the permutation results for the regions A:A, A:X, and X:X, each of which is a list with the six different LOD scores. Independent permutations are performed in each region, n.perm is the number of permutations for the A:A region; additional permutations are are used for the A:X and X:X parts, as estimates of quantiles farther out into the tails are needed.

X chromosome

The X chromosome must be treated specially in QTL mapping.

As in scanone, if both males and females are included, male hemizygotes are allowed to be different from female homozygotes, and the null hypothesis must be changed in order to ensure that sex- or pgm-differences in the phenotype do not results in spurious linkage to the X chromosome. (See the help file for scanone.)

If n.perm is specified and perm.Xsp=TRUE, X-chromosome-specific permutations are performed, to obtain separate thresholds for the regions A:A, A:X, and X:X.

Author(s)

Karl W Broman, [email protected]; Hao Wu

References

Churchill, G. A. and Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

Dempster, A. P., Laird, N. M. and Rubin, D. B. (1977) Maximum likelihood from incomplete data via the EM algorithm. J. Roy. Statist. Soc. B, 39, 1–38.

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Lander, E. S. and Botstein, D. (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

Soller, M., Brody, T. and Genizi, A. (1976) On the power of experimental designs for the detection of linkage between marker loci and quantitative loci in crosses between inbred lines. Theor. Appl. Genet. 47, 35–39.

See Also

plot.scantwo, summary.scantwo, scanone, max.scantwo, summary.scantwoperm, c.scantwoperm

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=5)
out.2dim <- scantwo(fake.f2, method="hk")
plot(out.2dim)

# permutations

## Not run: permo.2dim <- scantwo(fake.f2, method="hk", n.perm=1000)
summary(permo.2dim, alpha=0.05)

# summary with p-values
summary(out.2dim, perms=permo.2dim, pvalues=TRUE,
        alphas=c(0.05, 0.10, 0.10, 0.05, 0.10))

# covariates
data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=10)

ac <- pull.pheno(fake.bc, c("sex","age"))
ic <- pull.pheno(fake.bc, "sex")

out <- scantwo(fake.bc, method="hk", pheno.col=1,
               addcovar=ac, intcovar=ic)
plot(out)

Permutation test for 2d genome scan by Haley-Knott regression

Description

Perform a permutation test with a two-dimensional genome scan with a two-QTL model, with possible allowance for additive covariates, by Haley-Knott regression.

Usage

scantwopermhk(cross, chr, pheno.col=1,
              addcovar=NULL, weights=NULL, n.perm=1,
              batchsize=1000,
              perm.strata=NULL, perm.Xsp=NULL,
              verbose=FALSE, assumeCondIndep=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes for which LOD scores should be calculated. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. This should be a single value (numeric index or character string for a phenotype name), but it may also be a vector of numeric values with length equal to the number of individuals in the cross, in which case it is taken to be a vector of individuals' phenotypes.

addcovar

Additive covariates.

weights

Optional weights of individuals. Should be either NULL or a vector of length n.ind containing positive weights. Used only in the case model="normal".

n.perm

Number of permutation replicates.

batchsize

If n.perm > batchsize, permutations will be run in batches of no more than batchsize permutations.

perm.strata

Used to perform a stratified permutation test. This should be a vector with the same number of individuals as in the cross data. Unique values indicate the individual strata, and permutations will be performed within the strata.

perm.Xsp

If TRUE, run separate permutations for A:A, A:X, and X:X. In this case, n.perm refers to the number of permutations for the A:A part; more permutations are used for the A:X and X:X parts, as estimates of quantiles farther out into the tails are needed.

verbose

If TRUE, display information about the progress of calculations.

assumeCondIndep

If TRUE, assume conditional independence of QTL genotypes given marker genotypes. This is an approximation, but it may speed things up.

Details

This is a scaled-back version of the permutation test provided by scantwo: only for a normal model with Haley-Knott regression, and not allowing interactive covariates.

This is an attempt to speed things up and attentuate the memory usage problems in scantwo.

In the case of perm.Xsp=TRUE (X-chr-specific thresholds), we use a stratified permutation test, stratified by sex and cross-direction.

Value

A list with six different LOD scores from each of the permutation replicates. First, the maximum LOD score for the full model (two QTLs plus an interaction). Second, for each pair of chromosomes, we take the difference between the full LOD and the maximum single-QTL LOD for those two chromosomes, and then maximize this across chromosome pairs. Third, for each pair of chromosomes we take the difference between the maximum full LOD and the maximum additive LOD, and then maximize this across chromosome pairs. Fourth, the maximum LOD score for the additive QTL model. Fifth, for each pair of chromosomes, we take the difference between the additive LOD and the maximum single-QTL LOD for those two chromosomes, and then maximize this across chromosome pairs. Finally, the maximum single-QTL LOD score (that is, from a single-QTL scan). The latter is not used in summary.scantwoperm, but does get calculated at each permutation, so we include it for the sake of completeness.

If perm.Xsp=TRUE, this is a list of lists, for the A:A, A:X, and X:X sections, each being a list as described above.

Author(s)

Karl W Broman, [email protected]; Hao Wu

References

Churchill, G. A. and Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

See Also

scantwo, plot.scantwoperm, summary.scantwoperm, c.scantwoperm

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=5)
operm <- scantwopermhk(fake.f2, n.perm=2)
summary(operm, alpha=0.05)

Shift starting points in genetic maps

Description

Shift starting points in a genetic map to a set of defined positions

Usage

shiftmap(object, offset=0)

Arguments

object

An object of class cross (see read.cross for details) or map (see sim.map for details).

offset

Defines the starting position for each chromosome. This should be a single value (to be used for all chromosomes) or a vector with length equal to the number of chromosomes, defining individual starting positions for each chromosome. For a sex-specific map (as in a 4-way cross), we use the same offset for both the male and female maps.

Value

If the input is a map object, a map object is returned; if the input is a cross object, a cross object is returned. In either case, the positions of markers are shifted so that the starting positions are as in offset.

Author(s)

Karl W Broman, [email protected]

See Also

replace.map, est.map

Examples

data(hyper)
shiftedhyper <- shiftmap(hyper, offset=0)
par(mfrow=c(1,2))
plotMap(hyper, shift=FALSE, alternate.chrid=TRUE)
plotMap(shiftedhyper, shift=FALSE, alternate.chrid=TRUE)

Simulate a QTL experiment

Description

Simulates data for a QTL experiment using a model in which QTLs act additively.

Usage

sim.cross(map, model=NULL, n.ind=100,
         type=c("f2", "bc", "4way", "risib", "riself",
           "ri4sib", "ri4self", "ri8sib", "ri8self", "bcsft"),
          error.prob=0, missing.prob=0, partial.missing.prob=0,
          keep.qtlgeno=TRUE, keep.errorind=TRUE, m=0, p=0,
      map.function=c("haldane","kosambi","c-f","morgan"),
          founderGeno, random.cross=TRUE, ...)

Arguments

map

A list whose components are vectors containing the marker locations on each of the chromosomes.

model

A matrix where each row corresponds to a different QTL, and gives the chromosome number, cM position and effects of the QTL.

n.ind

Number of individuals to simulate.

type

Indicates whether to simulate an intercross (f2), a backcross (bc), a phase-known 4-way cross (4way), or recombinant inbred lines (by selfing or by sib-mating, and with the usual 2 founder strains or with 4 or 8 founder strains).

error.prob

The genotyping error rate.

missing.prob

The rate of missing genotypes.

partial.missing.prob

When simulating an intercross or 4-way cross, this gives the rate at which markers will be incompletely informative (i.e., dominant or recessive).

keep.qtlgeno

If TRUE, genotypes for the simulated QTLs will be included in the output.

keep.errorind

If TRUE, and if error.prob > 0, the identity of genotyping errors will be included in the output.

m

Interference parameter; a non-negative integer. 0 corresponds to no interference.

p

Probability that a chiasma comes from the no-interference mechanism

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions.

founderGeno

For 4- or 8-way RIL, the genotype data of the founder strains, as a list whose components are numeric matrices (no. markers x no. founders), one for each chromosome.

random.cross

For 4- or 8-way RIL, indicates whether the order of the founder strains should be randomized, independently for each RIL, or whether all RIL be derived from a common cross. In the latter case, for a 4-way RIL, the cross would be (AxB)x(CxD).

...

For type = "bcsft", additional arguments passed to sim.cross.bcsft.

Details

Meiosis is assumed to follow the Stahl model for crossover interference (see the references, below), of which the no interference model and the chi-square model are special cases. Chiasmata on the four-strand bundle are a superposition of chiasmata from two different mechanisms. With probability p, they arise by a mechanism exhibiting no interference; the remainder come from a chi-square model with inteference parameter m. Note that m=0 corresponds to no interference, and with p=0, one gets a pure chi-square model.

If a chromosomes has class X, it is assumed to be the X chromosome, and is assumed to be segregating in the cross. Thus, in an intercross, it is segregating like a backcross chromosome. In a 4-way cross, a second phenotype, sex, will be generated.

QTLs are assumed to act additively, and the residual phenotypic variation is assumed to be normally distributed with variance 1.

For a backcross, the effect of a QTL is a single number corresponding to the difference between the homozygote and the heterozygote.

For an intercross, the effect of a QTL is a pair of numbers, (a,da,d), where aa is the additive effect (half the difference between the homozygotes) and dd is the dominance deviation (the difference between the heterozygote and the midpoint between the homozygotes).

For a four-way cross, the effect of a QTL is a set of three numbers, (a,b,ca,b,c), where, in the case of one QTL, the mean phenotype, conditional on the QTL genotyping being AC, BC, AD or BD, is aa, bb, cc or 0, respectively.

Value

An object of class cross. See read.cross for details.

If keep.qtlgeno is TRUE, the cross object will contain a component qtlgeno which is a matrix containing the QTL genotypes (with complete data and no errors), coded as in the genotype data.

If keep.errorind is TRUE and errors were simulated, each component of geno will each contain a matrix errors, with 1's indicating simulated genotyping errors.

Recombinant inbred lines

In the simulation of recombinant inbred lines (RIL), we simulate a single individual from each line, and no phenotypes are simulated (so the argument model is ignored).

The types riself and risib are the usual two-way RIL.

The types ri4self, ri4sib, ri8self, and ri8sib are RIL by selfing or sib-mating derived from four or eight founding parental strains.

For the 4- and 8-way RIL, one must include the genotypes of the founding individuals; these may be simulated with simFounderSnps. Also, the output cross will contain a component cross, which is a matrix with rows corresponding to RIL and columns corresponding to the founders, indicating order of the founder strains in the crosses used to generate the RIL.

The coding of genotypes in 4- and 8-way RIL is rather complicated. It is a binary encoding of which founder strains' genotypes match the RIL's genotype at a marker, and not that this is specific to the order of the founders in the crosses used to generate the RIL. For example, if an RIL generated from 4 founders has the 1 allele at a SNP, and the four founders have SNP alleles 0, 1, 0, 1, then the RIL allele matches that of founders B and D. If the RIL was derived by the cross (AxB)x(CxD), then the RIL genotype would be encoded 221+231=62^{2-1} + 2^{3-1} = 6. If the cross was derived by the cross (DxA)x(CxB), then the RIL genotype would be encoded 211+241=92^{1-1} + 2^{4-1} = 9. These get reorganized after calls to calc.genoprob, sim.geno, or argmax.geno, and this approach simplifies the hidden Markov model (HMM) code.

For the 4- and 8-way RIL, genotyping errors are simulated only if the founder genotypes are 0/1 SNPs.

Author(s)

Karl W Broman, [email protected]

References

Copenhaver, G. P., Housworth, E. A. and Stahl, F. W. (2002) Crossover interference in arabidopsis. Genetics 160, 1631–1639.

Foss, E., Lande, R., Stahl, F. W. and Steinberg, C. M. (1993) Chiasma interference as a function of genetic distance. Genetics 133, 681–691.

Zhao, H., Speed, T. P. and McPeek, M. S. (1995) Statistical analysis of crossover interference using the chi-square model. Genetics 139, 1045–1056.

Broman, K. W. (2005) The genomes of recombinant inbred lines Genetics 169, 1133–1146.

Teuscher, F. and Broman, K. W. (2007) Haplotype probabilities for multiple-strain recombinant inbred lines. Genetics 175, 1267–1274.

See Also

sim.map, read.cross, fake.f2, fake.bc fake.4way, simFounderSnps

Examples

# simulate a genetic map
map <- sim.map()


### simulate 250 intercross individuals with 2 QTLs
fake <- sim.cross(map, type="f2", n.ind=250,
                  model = rbind(c(1,45,1,1),c(5,20,0.5,-0.5)))


### simulate 100 backcross individuals with 3 QTL
# a 10-cM map model after the mouse
data(map10)

fakebc <- sim.cross(map10, type="bc", n.ind=100,
                    model=rbind(c(1,45,1), c(5,20,1), c(5,50,1)))


### simulate 8-way RIL by sibling mating
# get lengths from the above 10-cM map
L <- ceiling(sapply(map10, max))

# simulate a 1 cM map
themap <- sim.map(L, n.mar=L+1, eq.spacing=TRUE)

# simulate founder genotypes
pg <- simFounderSnps(themap, "8")

# simulate the 8-way RIL by sib mating (256 lines)
ril <- sim.cross(themap, n.ind=256, type="ri8sib", founderGeno=pg)

Simulate genotypes given observed marker data

Description

Uses the hidden Markov model technology to simulate from the joint distribution Pr(g | O) where g is the underlying genotype vector and O is the observed multipoint marker data, with possible allowance for genotyping errors.

Usage

sim.geno(cross, n.draws=16, step=0, off.end=0, error.prob=0.0001,
         map.function=c("haldane","kosambi","c-f","morgan"),
         stepwidth=c("fixed", "variable", "max"))

Arguments

cross

An object of class cross. See read.cross for details.

n.draws

Number of simulation replicates to perform.

step

Maximum distance (in cM) between positions at which the simulated genotypes will be drawn, though for step=0, genotypes are drawn only at the marker locations.

off.end

Distance (in cM) past the terminal markers on each chromosome to which the genotype simulations will be carried.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions.

stepwidth

Indicates whether the intermediate points should with fixed or variable step sizes. We recommend using "fixed"; "variable" was included for the qtlbim package (https://cran.r-project.org/src/contrib/Archive/qtlbim/). The "max" option inserts the minimal number of intermediate points so that the maximum distance between points is step.

Details

After performing the forward-backward equations, we draw from Pr(g1=vO)Pr(g_1 = v | O) and then Pr(gk+1=vO,gk=u)Pr(g_{k+1} = v | O, g_k = u).

In the case of the 4-way cross, with a sex-specific map, we assume a constant ratio of female:male recombination rates within the inter-marker intervals.

Value

The input cross object is returned with a component, draws, added to each component of cross$geno. This is an array of size [n.ind x n.pos x n.draws] where n.pos is the number of positions at which the simulations were performed and n.draws is the number of replicates. Attributes "error.prob", "step", and "off.end" are set to the values of the corresponding arguments, for later reference.

Author(s)

Karl W Broman, [email protected]

See Also

calc.genoprob, argmax.geno

Examples

data(fake.f2)

fake.f2 <- sim.geno(fake.f2, step=2, n.draws=8)

Simulate a genetic map

Description

Simulate the positions of markers on a genetic map.

Usage

sim.map(len=rep(100,20), n.mar=10, anchor.tel=TRUE,
        include.x=TRUE, sex.sp=FALSE, eq.spacing=FALSE)

Arguments

len

A vector specifying the chromosome lengths (in cM)

n.mar

A vector specifying the number of markers per chromosome.

anchor.tel

If true, markers at the two telomeres will always be included, so if n.mar = 1 or 2, we'll give just the two telomeric markers.

include.x

Indicates whether the last chromosome should be considered the X chromosome.

sex.sp

Indicates whether to create sex-specific maps, in which case the output will be a vector of 2-row matrices, with rows corresponding to the maps for the two sexes.

eq.spacing

If TRUE, markers will be equally spaced.

Details

Aside from the telomeric markers, marker positions are simulated as iid Uniform(0,L0,L). If len or n.mar has just one element, it is expanded to the length of the other argument. If they both have just one element, only one chromosome is simulated.

If eq.spacing is TRUE, markers are equally spaced between 0 and LL. If anchor.tel is FALSE, telomeric markers are not included.

Value

A list of vectors, each specifying the locations of the markers. Each component of the list is given class A or X, according to whether it is autosomal or the X chromosome.

Author(s)

Karl W Broman, [email protected]

See Also

sim.cross, plotMap, replace.map, pull.map

Examples

# simulate 4 autosomes, each with 10 markers
map <- sim.map(c(100,90,80,40), 10, include.x=FALSE)
plotMap(map)

# equally spaced markers
map2 <- sim.map(c(100,90,80,40), 10, include.x=FALSE, eq.spacing=TRUE)
plot(map2)

Simulate founder SNPs for a multiple-strain RIL

Description

Simulate genotype data for the founding strains for a panel of multiple-strain RIL.

Usage

simFounderSnps(map, n.str=c("4","8"), pat.freq)

Arguments

map

A list whose components are vectors containing the marker locations on each of the chromosomes.

n.str

Number of founding strains (4 or 8).

pat.freq

Frequency of SNP genotype patterns in the founder (a vector of length n.str/2 + 1): (monoallelic, SNP unique to one founder, SNP present in 2 founders, [and, for the case of 8 founders, SNP in 3/8 founders, SNP in 4/8 founders].)

Details

The SNPs are simulated to be in linkage equilibrium.

Value

A vector of the same length as there are chromosomes in map, with each component being a matrix of 0's and 1's, of dim n.str x n.mar.

Author(s)

Karl W Broman, [email protected]

See Also

sim.map, sim.cross

Examples

data(map10)
x <- simFounderSnps(map10, "8", c(0, 0.5, 0.2, 0.2, 0.1))

Simulate a set of intercrosses for a single diallelic QTL

Description

Simulate a set of intercrosses with a single diallelic QTL.

Usage

simPhyloQTL(n.taxa=3, partition, crosses, map, n.ind=100, model,
            error.prob=0, missing.prob=0, partial.missing.prob=0,
            keep.qtlgeno=FALSE, keep.errorind=TRUE, m=0, p=0,
        map.function=c("haldane","kosambi","c-f","morgan"))

Arguments

n.taxa

Number of taxa (i.e., strains).

partition

A vector of character strings of the form "AB|CD" or "A|BCD" indicating, for each QTL, which taxa have which allele. If missing, simulate under the null hypothesis of no QTL.

crosses

A vector of character strings indicating the crosses to do (for the form "AB", "AC", etc.). These will be sorted and then only unique ones used. If missing, all crosses will be simulated.

map

A list whose components are vectors containing the marker locations on each of the chromosomes.

n.ind

The number of individuals in each cross. If length 1, all crosses will have the same number of individuals; otherwise the length should be the same as crosses.

model

A matrix where each row corresponds to a different QTL, and gives the chromosome number, cM position and effects of the QTL (assumed to be the same in each cross in which the QTL is segregating).

error.prob

The genotyping error rate.

missing.prob

The rate of missing genotypes.

partial.missing.prob

When simulating an intercross or 4-way cross, this gives the rate at which markers will be incompletely informative (i.e., dominant or recessive).

keep.qtlgeno

If TRUE, genotypes for the simulated QTLs will be included in the output.

keep.errorind

If TRUE, and if error.prob > 0, the identity of genotyping errors will be included in the output.

m

Interference parameter; a non-negative integer. 0 corresponds to no interference.

p

Probability that a chiasma comes from the no-interference mechanism

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions.

Details

Meiosis is assumed to follow the Stahl model for crossover interference (see the references, below), of which the no interference model and the chi-square model are special cases. Chiasmata on the four-strand bundle are a superposition of chiasmata from two different mechanisms. With probability p, they arise by a mechanism exhibiting no interference; the remainder come from a chi-square model with inteference parameter m. Note that m=0 corresponds to no interference, and with p=0, one gets a pure chi-square model.

QTLs are assumed to act additively, and the residual phenotypic variation is assumed to be normally distributed with variance 1.

The effect of a QTL is a pair of numbers, (a,da,d), where aa is the additive effect (half the difference between the homozygotes) and dd is the dominance deviation (the difference between the heterozygote and the midpoint between the homozygotes).

Value

A list with each component being an object of class cross. See read.cross for details. The names (e.g. "AB", "AC", "BC") indicate the crosses.

If keep.qtlgeno is TRUE, each cross object will contain a component qtlgeno which is a matrix containing the QTL genotypes (with complete data and no errors), coded as in the genotype data.

If keep.errorind is TRUE and errors were simulated, each component of geno in each cross will each contain a matrix errors, with 1's indicating simulated genotyping errors.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Kim, S., An\'e, C. and Payseur, B. A. Mapping quantitative trait loci to a phylogenetic tree. In preparation.

See Also

scanPhyloQTL, inferredpartitions, summary.scanPhyloQTL, max.scanPhyloQTL, plot.scanPhyloQTL, sim.cross, read.cross

Examples

## Not run: 
# example map; drop X chromosome
data(map10)
map10 <- map10[1:19]

# simulate data
x <- simPhyloQTL(4, partition="AB|CD", crosses=c("AB", "AC", "AD"),
                 map=map10, n.ind=150,
                 model=c(1, 50, 0.5, 0))

# run calc.genoprob on each cross
x <- lapply(x, calc.genoprob, step=2)

# scan genome, at each position trying all possible partitions
out <- scanPhyloQTL(x, method="hk")

# maximum peak
max(out, format="lod")

# approximate posterior probabilities at peak
max(out, format="postprob")

# all peaks above a threshold for LOD(best) - LOD(2nd best)
summary(out, threshold=1, format="lod")

# all peaks above a threshold for LOD(best), showing approx post'r prob
summary(out, format="postprob", threshold=3)

# plot of results
plot(out)

## End(Not run)

Simulates missing genotype data

Description

Simulate missing genotype data by removing some genotype data from the cross object

Usage

simulatemissingdata(cross, percentage = 5)

Arguments

cross

An object of class cross. See read.cross for details.

percentage

How much of the genotype data do we need to randomly drop?

Value

An object of class cross with percentage

Author(s)

Danny Arends [email protected]

See Also

Examples

data(multitrait)
multitrait <- fill.geno(multitrait)
multimissing5 <- simulatemissingdata(multitrait,perc=5)
perc <- (sum(nmissing(multimissing5))/sum(ntyped(multimissing5)))

Stepwise selection for multiple QTL

Description

Performs forward/backward selection to identify a multiple QTL model, with model choice made via a penalized LOD score, with separate penalties on main effects and interactions.

Usage

stepwiseqtl(cross, chr, pheno.col=1, qtl, formula, max.qtl=10, covar=NULL,
            method=c("imp", "hk"), model=c("normal", "binary"),
            incl.markers=TRUE, refine.locations=TRUE,
            additive.only=FALSE, scan.pairs=FALSE, penalties,
            keeplodprofile=TRUE, keeptrace=FALSE, verbose=TRUE,
            tol=1e-4, maxit=1000, require.fullrank=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider in search for QTL. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

pheno.col

Column number in the phenotype matrix which should be used as the phenotype. One may also give character strings matching the phenotype names. Finally, one may give a numeric vector of phenotypes, in which case it must have the length equal to the number of individuals in the cross, and there must be either non-integers or values < 1 or > no. phenotypes; this last case may be useful for studying transformations.

qtl

Optional QTL object (of class "qtl", as created by makeqtl) to use as a starting point.

formula

Optional formula to define the QTL model to be used as a starting point.

max.qtl

Maximum number of QTL to which forward selection should proceed.

covar

Data frame of additive covariates.

method

Indicates whether to use multiple imputation or Haley-Knott regression.

model

The phenotype model: the usual model or a model for binary traits

incl.markers

If FALSE, do calculations only at points on an evenly spaced grid.

refine.locations

If TRUE, use refineqtl to refine the QTL locations after each step of forward and backward selection.

additive.only

If TRUE, allow only additive QTL models; if FALSE, consider also pairwise interactions among QTL.

scan.pairs

If TRUE, perform a two-dimensional, two-QTL scan at each step of forward selection.

penalties

Vector of three (or six) values indicating the penalty on the number of QTL terms. If three values, these are the penalties on main effects and heavy and light penalties on interactions. If six values, these include X-chr-specific penalties, and the values are: main effect for autosomes, main effect for X chr, heavy penalty on A:A interactions, light penalty on A:A interactions, penalty on A:X interactions, and penalty on X:X interactions. See the Details below. If missing, default values are used that are based on simulations of backcrosses and intercrosses with genomes modeled after that of the mouse.

keeplodprofile

If TRUE, keep the LOD profiles from the last iteration as attributes to the output.

keeptrace

If TRUE, keep information on the sequence of models visited through the course of forward and backward selection as an attribute to the output.

verbose

If TRUE, give feedback about progress. If verbose is an integer > 1, even more information is printed.

tol

Tolerance for convergence for the binary trait model.

maxit

Maximum number of iterations for fitting the binary trait model.

require.fullrank

If TRUE, give LOD=0 when covariate matrix in the linear regression is not of full rank.

Details

We seek to identify the model with maximal penalized LOD score. The penalized LOD score, defined in Manichaikul et al. (2009), is the LOD score for the model (the log10\log_{10} likelihood ratio comparing the model to the null model with no QTL) with penalties on the number of QTL and QTL:QTL interactions.

We consider QTL models allowing pairwise interactions among QTL but with an enforced hierarchy in which inclusion of a pairwise interaction requires the inclusion of both of the corresponding main effects. Additive covariates may be included, but currently we do not explore QTL:covariate interactions. Also, the penalized LOD score criterion is currently defined only for autosomal loci, and results with the X chromosome should be considered with caution.

The penalized LOD score is of the form pLOD(γ)=LOD(γ)TmpmThphTlplpLOD(\gamma) = LOD(\gamma) - T_m p_m - T_h p_h - T_l p_l where γ\gamma denotes a model, pmp_m is the number of QTL in the model ("main effects"), php_h is the number of pairwise interactions that will be given a heavy interaction penalty, plp_l is the number of pairwise interactions that will be given a light interaction penalty, TmT_m is the penalty on main effects, ThT_h is the heavy interaction penalty, and TlT_l is the light interaction penalty. The penalties argument is the vector (Tm,Th,Tl)(T_m, T_h, T_l). If TlT_l is missing (penalties has a vector of length 2), we assume Tl=ThT_l = T_h, and so all pairwise interactions are assigned the same penalty.

The "heavy" and "light" interaction penalties can be a bit confusing. Consider the clusters of QTL that are connected via one or more pairwise interactions. To each such cluster, we assign at most one "light" interaction penalty, and give all other pairwise interactions the heavy interaction penalty. In other words, if pip_i is the total number of pairwise interactions for a QTL model, we let plp_l be the number of clusters of connected QTL with at least one pairwise interaction, and then let phpiplp_h - p_i - p_l.

Let us give an explicit example. Consider a model with 6 QTL, and with interactions between QTL 2 and 3, QTL 4 and 5 and QTL 4 and 6 (so we have the model formula y ~ Q1 + Q2 + Q3 + Q4 + Q5 + Q6 + Q2:Q3 + Q4:Q5 + Q4:Q6). There are three clusters of connected QTL: (1), (2,3) and (4,5,6). We would assign 6 main effect penalties (TmT_m), 2 light interaction penalties (TlT_l), and 1 heavy interaction penalty (ThT_h).

Manichaikul et al. (2009) described a system for deriving the three penalties on the basis of permutation results from a two-dimensional, two-QTL genome scan (as calculated with scantwo). These may be calculated with the function calc.penalties.

A forward/backward search method is used, with the aim to optimize the penalized LOD score criterion. That is, we seek to identify the model with maximal the penalized LOD score. The search algorithm was based closely on an algorithm described by Zeng et al. (1999).

We use forward selection to a model of moderate size (say 10 QTL), followed by backward elimination all the way to the null model. The chosen model is that which optimizes the penalized LOD score criterion, among all models visited. The detailed algorithm is as follows. Note that if additive.only=TRUE, no pairwise interactions are considered.

  1. Start at the null model, and perform a single-QTL genome scan, and choose the position giving the largest LOD score. If scan.pairs=TRUE, start with a two-dimensional, two-QTL genome scan instead. If an initial QTL model were defined through the arguments qtl and formula, start with this model and jump immediately to step 2.

  2. With a fixed QTL model in hand:

    1. Scan for an additional additive QTL.

    2. For each QTL in the current model, scan for an additional interacting QTL.

    3. If there are \ge 2 QTL in the current model, consider adding one of the possible pairwise interactions.

    4. If scan.pairs=TRUE perform a two-dimensional, two-QTL scan, seeking to add a pair of novel QTL, either additive or interacting.

    5. Step to the model that gives the largest value for the model comparison criterion, among those considered at the current step.

  3. Refine the locations of the QTL in the current model (if refine.locations=TRUE).

  4. Repeat steps 2 and 3 up to a model with some pre-determined number of loci.

  5. Perform backward elimination, all the way back to the null model. At each step, consider dropping one of the current main effects or interactions; move to the model that maximizes the model comparison criterion, among those considered at this step. Follow this with a refinement of the locations of the QTL.

  6. Finally, choose the model having the largest model comparison criterion, among all models visited.

In this forward/backward algorithm, it is likely best to build up to an overly large model and then prune it back. Note that there is no "stopping rule"; the chosen model is that which optimizes the model comparison criterion, among all models visited. The search can be time consuming, particularly if a two-dimensional scan is performed at each forward step. Such two-dimensional scans may be useful for identifying QTL linked in repulsion (having effects of opposite sign) or interacting QTL with limited marginal effects, but our limited experience suggests that they are not necessary; important linked or interacting QTL pairs can be picked up in the forward selection to a large model, and will be retained in the backward elimination phase.

Value

The output is a representation of the best model, as measured by the penalized LOD score (see Details), among all models visited. This is QTL object (of class "qtl", as produced by makeqtl), with attributes "formula", indicating the model formula, and "pLOD" indicating the penalized LOD score.

If keeplodprofile=TRUE, LOD profiles from the last pass through the refinement algorithm are retained as an attribute, "lodprofile", to the object. These may be plotted with plotLodProfile.

If keeptrace=TRUE, the output will contain an attribute "trace" containing information on the best model at each step of forward and backward elimination. This is a list of objects of class "compactqtl", which is similar to a QTL object (as produced by makeqtl) but containing just a vector of chromosome IDs and positions for the QTL. Each will also have attributes "formula" (containing the model formula) and "pLOD" (containing the penalized LOD score.

Methods

imp: multiple imputation is used, as described by Sen and Churchill (2001).

hk: Haley-Knott regression is used (regression of the phenotypes on the multipoint QTL genotype probabilities), as described by Haley and Knott (1992).

Author(s)

Karl W Broman, [email protected]

References

Manichaikul, A., Moon, J. Y., Sen, Ś, Yandell, B. S. and Broman, K. W. (2009) A model selection approach for the identification of quantitative trait loci in experimental crosses, allowing epistasis. Genetics, 181, 1077–1086.

Broman, K. W. and Speed, T. P. (2002) A model selection approach for the identification of quantitative trait loci in experimental crosses (with discussion). J Roy Stat Soc B 64, 641–656, 731–775.

Haley, C. S. and Knott, S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.

Sen, Ś. and Churchill, G. A. (2001) A statistical framework for quantitative trait mapping. Genetics 159, 371–387.

Zeng, Z.-B., Kao, C.-H. and Basten, C. J. (1999) Estimating the genetic architecture of quantitative traits. Genetical Research, 74, 279–289.

See Also

calc.penalties, plotModel, makeqtl, fitqtl, refineqtl, addqtl, addpair

Examples

data(fake.bc)

## Not run: fake.bc <- calc.genoprob(fake.bc, step=2.5)

outsw <- stepwiseqtl(fake.bc, max.qtl=3, method="hk", keeptrace=TRUE)

# best model
outsw
plotModel(outsw)

# path through model space
thetrace <- attr(outsw, "trace")

# plot of these
par(mfrow=c(3,3))
for(i in seq(along=thetrace))
  plotModel(thetrace[[i]], main=paste("pLOD =",round(attr(thetrace[[i]],"pLOD"), 2)))

Strip partially informative genotypes

Description

Replace all partially informative genotypes (e.g., dominant markers in an intercross) with missing values.

Usage

strip.partials(cross, verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

verbose

If TRUE, print the number of genotypes removed.

Value

The same class cross object as in the input, but with partially informative genotypes made missing.

Author(s)

Karl W Broman, [email protected]

See Also

plotMissing, plotInfo

Examples

data(listeria)
sum(nmissing(listeria))
listeria <- strip.partials(listeria)
sum(nmissing(listeria))

Subsetting data for QTL experiment

Description

Pull out a specified set of chromosomes and/or individuals from a cross object.

Usage

## S3 method for class 'cross'
subset(x, chr, ind, ...)
## S3 method for class 'cross'
x[chr, ind]

Arguments

x

An object of class cross. See read.cross for details.

chr

Optional vector specifying which chromosomes to keep or discard. This may be a logical, numeric, or character string vector. See Details, below.

ind

Optional vector specifying which individuals to keep discard. This may be a logical, numeric or chacter string vector. See Details, below.

...

Ignored at this point.

Details

The chr argument may be a logical vector with length equal to the number of chromosomes in the input cross x. Alternatively, it should be a vector of character strings referring to chromosomes by name. Numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered.

If the ind argument is a logical vector (TRUE/FALSE), it should have length equal to the number of individuals in the input cross x. The individuals with corresponding TRUE values are retained.

If the ind argument is numeric, it should have values either between 1 and the number of individuals in the input cross x (in which case these individuals will be retained), or it should have values between -1 and -n, where n is the number of individuals in the input cross x, in which case all except these individuals will be retained.

If the input cross object x contains individual identifiers (a phenotype column labeled "id" or "ID"), and if the ind argument contains character strings, then these will be matched against the individual identifiers. If all values in ind are preceded by a -), we omit those individuals whose IDs match those in ind. Otherwise, we retain those individuals whose IDs match those in ind.

Value

The input cross object, but with only the specified subset of the data.

Author(s)

Karl W Broman, [email protected]

See Also

pull.map, drop.markers, subset.map

Examples

data(fake.f2)
fake.f2.A <- subset(fake.f2, chr=c("5","13"))
fake.f2.B <- subset(fake.f2, ind = -c(1,5,10))
fake.f2.C <- subset(fake.f2, chr=1:5, ind=1:50)

data(listeria)
y <- pull.pheno(listeria, 1)
listeriaB <- subset(listeria, ind = (!is.na(y) & y < 264))

# individual identifiers
listeria$pheno$ID <- paste("mouse", 1:nind(listeria), sep="")
listeriaC <- subset(listeria, ind=c("mouse1","mouse11","mouse21"))
listeriaD <- subset(listeria, ind=c("-mouse1","-mouse11","-mouse21"))

# you can also use brackets (like matrix with rows=chromosomes and columns=individuals)
temp <- listeria[c("5","13"),]  # chr 5 and 13
temp <- listeria[ , 1:10]       # first ten individuals
temp <- listeria[5, 1:10]       # chr 5 for first ten individuals

Subsetting chromosomes for a genetic map

Description

Pull out a specified set of chromosomes from a map object.

Usage

## S3 method for class 'map'
subset(x, ...)
## S3 method for class 'map'
x[...]

Arguments

x

A list whose components are vectors of marker locations.

...

Vector of chromosome indices.

Value

The input map object, but with only the specified subset of chromosomes.

Author(s)

Karl W Broman, [email protected]

See Also

subset.cross

Examples

data(map10)
map10 <- subset(map10, chr=1:5)

# you can also use brackets
map10 <- map10[2:3]

Subsetting the results of a genome scan

Description

Pull out a specified set of chromosomes and/or LOD columns from scanone output.

Usage

## S3 method for class 'scanone'
subset(x, chr, lodcolumn, ...)

Arguments

x

An object of class scanone, output from scanone.

chr

Optional vector specifying which chromosomes to keep. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

lodcolumn

A vector specifying which LOD columns to keep (or, if negative), omit. These should be between 1 and the number of LOD columns in the input x.

...

Ignored at this point.

Value

The input scanone object, but with only the specified subset of the data.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scanone, scanone

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=2.5)
out <- scanone(fake.bc, method="hk", pheno.col=1:2)

summary(subset(out, chr=18:19), format="allpeaks")

Subsetting permutation test results

Description

Pull out results for a specified set LOD columns from permutation results from scanone.

Usage

## S3 method for class 'scanoneperm'
subset(x, repl, lodcolumn, ...)
## S3 method for class 'scanoneperm'
x[repl, lodcolumn]

Arguments

x

Permutation results from scanone, run with n.perm>0.

repl

A vector specifying which permutation replicates to keep or (if negative) omit.

lodcolumn

A vector specifying which LOD columns to keep or (if negative) omit. These should be between 1 and the number of LOD columns in the input x.

...

Ignored at this point.

Value

The input scanone permutation results, but with only the specified subset of the data.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scanoneperm, scanone, c.scanoneperm, cbind.scanoneperm, rbind.scanoneperm

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=5)
operm <- scanone(fake.bc, method="hk", pheno.col=1:2, n.perm=25)
operm2 <- subset(operm, lodcolumn=2)

# alternatively
operm2alt <- operm[,2]

Subsetting the results of a 2-d genome scan

Description

Pull out a specified set of chromosomes and/or LOD columns from scantwo output.

Usage

## S3 method for class 'scantwo'
subset(x, chr, lodcolumn, ...)

Arguments

x

An object of class scantwo, output from scantwo.

chr

Optional vector specifying which chromosomes to keep. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

lodcolumn

A vector specifying which LOD columns to keep (or, if negative), omit. These should be between 1 and the number of LOD columns in the input x.

...

Ignored at this point.

Value

The input scantwo object, but with only the specified subset of the data.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scantwo, scantwo

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc)
out <- scantwo(fake.bc, method="hk", pheno.col=1:2)

summary(subset(out, chr=18:19))

Subsetting two-dimensional permutation test results

Description

Pull out results for a specified set LOD columns from permutation results from scantwo.

Usage

## S3 method for class 'scantwoperm'
subset(x, repl, lodcolumn, ...)
## S3 method for class 'scantwoperm'
x[repl, lodcolumn]

Arguments

x

Permutation results from scantwo, run with n.perm>0.

repl

A vector specifying which permutation replicates to keep or (if negative) omit. Ignored in case of X-chr specific permutations

lodcolumn

A vector specifying which LOD columns to keep or (if negative) omit. These should be between 1 and the number of LOD columns in the input x.

...

Ignored at this point.

Value

The input scantwo permutation results, but with only the specified subset of the data.

Author(s)

Karl W Broman, [email protected]

See Also

summary.scantwoperm, scantwo, c.scantwoperm, rbind.scantwoperm

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=0)
operm <- scantwo(fake.bc, method="hk", pheno.col=1:2, n.perm=5)
operm2 <- subset(operm, lodcolumn=2)

# alternatively
operm2alt <- operm[,2]

Print pairs of individuals with similar genotype data.

Description

Prints a summary the output from comparegeno that includes pairs of individuals whose proportion of matching genotypes is above a chosen threshold.

Usage

## S3 method for class 'comparegeno'
summary(object, thresh=0.9, ...)

Arguments

object

An object of class comparegeno, the output of the function comparegeno.

thresh

Threshold on the proportion of matching genotypes.

...

Ignored at this point.

Value

A data frame with each row being a pair of individuals and columns including the individual identifiers (via getid, or just as numeric indexes) along with the proportion of matching genotypes.

Author(s)

Karl W Broman, [email protected]

See Also

comparegeno, plot.comparegeno

Examples

data(fake.f2)
cg <- comparegeno(fake.f2)
summary(cg, 0.7)

Print summary of QTL experiment

Description

Print summary information about a cross object.

Usage

## S3 method for class 'cross'
summary(object, ...)

Arguments

object

An object of class cross. See read.cross for details.

...

Ignored at this point.

Value

An object of class summary.cross containing a variety of summary information about the cross (this is generally printed automatically).

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, plot.cross, nind, nmar, nchr, totmar, nphe

Examples

data(fake.f2)
summary(fake.f2)

Summary of fit of qtl model

Description

Print summary information about the results of fitqtl.

Usage

## S3 method for class 'fitqtl'
summary(object, pvalues=TRUE, simple=FALSE, ...)

Arguments

object

Output from fitqtl.

pvalues

If FALSE, don't include p-values in the summary.

simple

If TRUE, don't include p-values or sums of squares in the summary.

...

Ignored at this point.

Value

An object of class summary.fitqtl, which is not all that different than the input, but when printed gives summary information about the results.

Author(s)

Hao Wu; Karl W Broman, [email protected]

See Also

fitqtl, makeqtl, scanqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 8, 13)
qp <- c(26, 56, 28)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

# fit model with 3 interacting QTLs interacting
# (performing a drop-one-term analysis)
lod <- fitqtl(fake.f2, pheno.col=1, qtl, formula=y~Q1*Q2*Q3,
              method="hk")
summary(lod)

Print summary of a QTL object

Description

Print summary information about a qtl object.

Usage

## S3 method for class 'qtl'
summary(object, ...)

Arguments

object

An object of class qtl, created by makeqtl.

...

Ignored at this point.

Value

An object of class summary.qtl, which is just a data.frame containing the chromosomes, positions, and number of possible genotypes for each QTL.

Author(s)

Karl W Broman, [email protected]

See Also

makeqtl

Examples

data(fake.f2)

# take out several QTLs and make QTL object
qc <- c(1, 6, 13)
qp <- c(25.8, 33.6, 18.63)
fake.f2 <- subset(fake.f2, chr=qc)

fake.f2 <- calc.genoprob(fake.f2, step=2, err=0.001)
qtl <- makeqtl(fake.f2, qc, qp, what="prob")

summary(qtl)

Print summary of ripple results

Description

Print marker orders, from the output of the function ripple, for which the log10 likelihood relative to the initial order is above a specified cutoff.

Usage

## S3 method for class 'ripple'
summary(object, lod.cutoff = -1, ...)

Arguments

object

An object of class ripple, the output of the function ripple.

lod.cutoff

Only marker orders with LOD score (relative to the initial order) above this cutoff will be displayed. For output of ripple in the case of minimization of the number of obligate crossovers, we double this argument and treat it as a cutoff for the number of obligate crossovers.

...

Ignored at this point.

Value

An object of class summary.ripple, whose rows correspond to marker orders with likelihood (or number of obligate crossovers) within some cutoff of the initial order. If no marker order, other than the initial one, has likelihood within the specified range, the initial and next-best orders are returned.

Author(s)

Karl W Broman, [email protected]

See Also

ripple, est.map, est.rf

Examples

## Not run: data(badorder)
rip1 <- ripple(badorder, 1, 7)
summary(rip1)

rip2 <- ripple(badorder, 1, 2, method="likelihood")
summary(rip2)

badorder <- switch.order(badorder, 1, rip2[2,])

## End(Not run)

Summarize the results of a genome scans

Description

Print the rows of the output from scanone that correspond to the maximum LOD for each chromosome, provided that they exceed some specified thresholds.

Usage

## S3 method for class 'scanone'
summary(object, threshold,
        format=c("onepheno", "allpheno", "allpeaks", "tabByCol", "tabByChr"),
        perms, alpha, lodcolumn=1, pvalues=FALSE,
        ci.function=c("lodint", "bayesint"), ...)

Arguments

object

An object output by the function scanone.

threshold

LOD score thresholds. Only peaks with LOD score above this value will be returned. This could be a single number or (for formats other than "onepheno") a threshold for each LOD score column. If alpha is specified, threshold should not be.

format

Format for the output. See Details, below.

perms

Optional permutation results used to derive thresholds or to calculate genome-scan-adjusted p-values. This must be consistent with the object input, in that it must have the same number of LOD score columns, though it can have just one column of permutation results, in which case they are reused for all LOD score columns in the scanone output, object. (These can also be permutation results from scantwo, which permutations for a one-dimensional scan.)

alpha

If perms are included, this is the significance level used to calculate thresholds for determining which peaks to pull out. If threshold is specified, alpha should not be.

lodcolumn

If format="onepheno", this indicates the LOD score column to focus on. This should be a single number between 1 and the number of LOD columns in the object input.

pvalues

If TRUE, include columns with genome-scan-adjusted p-values in the results. This requires that perms be provided.

ci.function

For formats "tabByCol" and "tabByChr", indicates the function to use to get approximate confidence intervals for QTL location.

...

For formats "tabByCol" and "tabByChr", additional arguments are passed to the function indicated by ci.function (for example, drop for lodint or prob for bayesint, or expandtomarkers for either).

Details

This function is used to report loci deemed interesting from a one-QTL genome scan (by scanone).

For format="onepheno", we focus on a single LOD score column, indicated by lodcolumn. The single largest LOD score peak on each chromosome is extracted. If threshold is specified, only those peaks with LOD meeting the threshold will be returned. If perms and alpha are specified, a threshold is calculated based on the permutation results in perms for the significance level alpha. If neither threshold nor alpha are specified, the peak on each chromosome is returned. Again note that with this format, only the LOD score column indicated by lodcolumn is considered in deciding which chromosomes to return, but the LOD scores from other columns, at the position with maximum LOD score in the lodcolumn column, are also returned.

For format="allpheno", we consider all LOD score columns, and pull out the position, on each chromosome, showing the largest LOD score. The output thus may contain multiple rows for a chromosome. Here threshold may be a vector of LOD score thresholds, one for each LOD score column, in which case only those positions for which a LOD score column exceeded its threshold are given. If threshold is a single number, it is applied to all of the LOD score columns. If alpha is specified, it must be a single significance level, applied for all LOD score columns, and again perms must be specified, and these are used to calculate the LOD score threshold for the significance level alpha.

For format="allpeaks", the output will contain, for each chromosome, the maximum LOD score for each LOD score column, at the position at which it achieved its maximum. Thus, the output will contain no more than one row per chromosome, but will contain the position and maximum LOD score for each of the LOD score columns. The arguments threshold and alpha may be specified as for the "allpheno" format. The results for a chromosome are returned if at least one of the LOD score columns exceeded its threshold.

For format="tabByCol", there will be a separate table for each LOD score column, with a single peak per chromosome. Included are columns indicating chromosome, peak position, lower and upper limits of the confidence interval calculated via lodint or bayesint, and lod score.

The output for format="tabByChr", is similar to that of format="tabByCol", but with results organized by chromosome rather than by LOD score column.

If pvalues=TRUE, and perms is specified, genome-scan-adjusted p-values are calculated for each LOD score column, and there are additional columns in the output containing these p-values.

In the case that X-chromosome specific permutations were performed (with perm.Xsp=TRUE in scanone), autosome- and X-chromosome specific thresholds and p-values are calculated by the method in Broman et al. (2006).

Value

An object of class summary.scanone, to be printed by print.summary.scanone.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Sen, Ś, Owens, S. E., Manichaikul, A., Southard-Smith, E. M. and Churchill G. A. (2006) The X chromosome in quantitative trait locus mapping. Genetics, 174, 2151–2158.

See Also

scanone, plot.scanone, max.scanone, subset.scanone, c.scanone, summary.scanoneperm c.scanoneperm

Examples

data(fake.bc)

fake.bc <- calc.genoprob(fake.bc, step=5)

# genome scan by Haley-Knott regression
out <- scanone(fake.bc, method="hk")

# permutation tests
## Not run: operm <- scanone(fake.bc, method="hk", n.perm=1000)


# peaks for all chromosomes
summary(out)

# results with LOD >= 3
summary(out, threshold=3)

# the same, but also showing the p-values
summary(out, threshold=3, perms=operm, pvalues=TRUE)

# results with LOD meeting the 0.05 threshold from the permutation results
summary(out, perms=operm, alpha=0.05)

# the same, also showing the p-values
summary(out, perms=operm, alpha=0.05, pvalues=TRUE)

##### summary with multiple phenotype results
out2 <- scanone(fake.bc, pheno.col=1:2, method="hk")

# permutations
## Not run: operm2 <- scanone(fake.bc, pheno.col=1:2, method="hk", n.perm=1000)


# results with LOD >= 2 for the 1st phenotype and >= 1 for the 2nd phenotype
#     using format="allpheno"
summary(out2, thr=c(2, 1), format="allpheno")

# The same with format="allpeaks"
summary(out2, thr=c(2, 1), format="allpeaks")

# The same with p-values
summary(out2, thr=c(2, 1), format="allpeaks", perms=operm2, pvalues=TRUE)

# results with LOD meeting the 0.05 significance level by the permutations
#     using format="allpheno"
summary(out2, format="allpheno", perms=operm2, alpha=0.05)

# The same with p-values
summary(out2, format="allpheno", perms=operm2, alpha=0.05, pvalues=TRUE)

# The same with format="allpeaks"
summary(out2, format="allpeaks", perms=operm2, alpha=0.05, pvalues=TRUE)

# format="tabByCol"
summary(out2, format="tabByCol", perms=operm2, alpha=0.05, pvalues=TRUE)

# format="tabByChr", but using bayes intervals
summary(out2, format="tabByChr", perms=operm2, alpha=0.05, pvalues=TRUE,
        ci.function="bayesint")

# format="tabByChr", but using 99% bayes intervals
summary(out2, format="tabByChr", perms=operm2, alpha=0.05, pvalues=TRUE,
        ci.function="bayesint", prob=0.99)

Bootstrap confidence interval for QTL location

Description

Calculates a bootstrap confidence interval for QTL location, using the bootstrap results from scanoneboot.

Usage

## S3 method for class 'scanoneboot'
summary(object, prob=0.95, expandtomarkers=FALSE, ...)

Arguments

object

Output from scanoneboot.

prob

Desired coverage.

expandtomarkers

If TRUE, the interval is expanded to the nearest flanking markers.

...

Ignored at this point.

Value

An object of class scanone, indicating the position with the maximum LOD, and indicating endpoints for the estimated bootstrap confidence interval.

Author(s)

Karl W Broman, [email protected]

See Also

scanoneboot, plot.scanoneboot, lodint, bayesint

Examples

## Not run: data(fake.f2)
fake.f2 <- calc.genoprob(fake.f2, step=1, err=0.001)
bootoutput <- scanoneboot(fake.f2, chr=13, method="hk")

summary(bootoutput)
## End(Not run)

LOD thresholds from scanone permutation results

Description

Print the estimated genome-wide LOD thresholds on the basis of permutation results from scanone (with n.perm > 0).

Usage

## S3 method for class 'scanoneperm'
summary(object, alpha=c(0.05, 0.10),
                    controlAcrossCol=FALSE, ...)

Arguments

object

Output from the function scanone with n.perm > 0.

alpha

Genome-wide significance levels.

controlAcrossCol

If TRUE, control error rate not just across the genome but also across the columns of LOD scores.

...

Ignored at this point.

Details

If there were autosomal data only or scanone was run with perm.Xsp=FALSE, genome-wide LOD thresholds are given; these are the 1-α\alpha quantiles of the genome-wide maximum LOD scores from the permutations.

If there were autosomal and X chromosome data and scanone was run with perm.Xsp=TRUE, autosome- and X-chromsome-specific LOD thresholds are given, by the method described in Broman et al. (2006). Let LAL_A and LXL_X be total the genetic lengths of the autosomes and X chromosome, respectively, and let LT=LA+LXL_T = L_A + L_X Then in place of α\alpha, we use

αA=1(1α)LA/LT\alpha_A = 1 - (1-\alpha)^{L_A/L_T}

as the significance level for the autosomes and

αX=1(1α)LX/LT\alpha_X = 1 - (1-\alpha)^{L_X/L_T}

as the significance level for the X chromosome. The result is a list with two matrices, one for the autosomes and one for the X chromosome.

If controlAcrossCol=TRUE, we use a trick to control the error rate not just across the genome but also across the LOD score columns. Namely, we convert each column of permutation results to ranks, and then for each permutation replicate we find the maximum rank across the columns. We then find the appropriate quantile of the maximized ranks, and then backtrack to the corresponding LOD score within each of the columns. See Burrage et al. (2010), right column on page 118.

Value

An object of class summary.scanoneperm, to be printed by print.summary.scanoneperm. If there were X chromosome data and scanone was run with perm.Xsp=TRUE, there are two matrices in the results, for the autosome and X-chromosome LOD thresholds.

Author(s)

Karl W Broman, [email protected]

References

Broman KW, Sen Ś, Owens SE, Manichaikul A, Southard-Smith EM, Churchill GA (2006) The X chromosome in quantitative trait locus mapping. Genetics, 174, 2151–2158.

Burrage LC, Baskin-Hill AE, Sinasac DS, Singer JB, Croniger CM, Kirby A, Kulbokas EJ, Daly MJ, Lander ES, Broman KW, Nadeau JH (2010) Genetic resistance to diet-induced obesity in chromosome substitution strains of mice. Mamm Genome, 21, 115–129.

Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

See Also

scanone, summary.scanone, plot.scanoneperm

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=2.5)

operm1 <- scanone(fake.f2, n.perm=100, method="hk")
summary(operm1)

operm2 <- scanone(fake.f2, n.perm=100, method="hk", perm.Xsp=TRUE)
summary(operm2)

# Add noise column
fake.f2$pheno$noise <- rnorm(nind(fake.f2))
operm3 <- scanone(fake.f2, pheno.col=c("phenotype", "noise"), n.perm=10, method="hk")
summary(operm3)
summary(operm3, controlAcrossCol=TRUE, alpha=c(0.05, 0.36))

Summarize the results a genome scan to map a QTL to a phylogenetic tree

Description

Print the maximum LOD scores for each partition on each chromosome, from the results of scanPhyloQTL.

Usage

## S3 method for class 'scanPhyloQTL'
summary(object, format=c("postprob", "lod"),
        threshold, ...)

Arguments

object

An object output by the function scanPhyloQTL.

format

Indicates whether to provide LOD scores or approximate posterior probabilities; see Details below.

threshold

A threshold determining which chromosomes should be output; see Details below.

...

Ignored at this point.

Details

This function is used to report chromosomes deemed interesting from a one-QTL genome scan to map QTL to a phylogenetic tree (by scanPhyloQTL).

For format="lod", the output contains the maximum LOD score for each partition on each chromosome (which do not necessarily occur at the same position). The position corresponds to the peak location for the partition with the largest LOD score on that chromosome. The last column is the overall maximum LOD (across partitions) on that chromosome. The second-to-last column is the inferred partition (i.e., that with the largest LOD score. The third-to-last column is the difference between the LOD score for the best partition and that for the second-best.

For format="postprob", the final column contains the maximum LOD score across partitions. But instead of providing the LOD scores for each partition, these are converted to approximate posterior probabilities under the assumption of a single diallelic QTL on that chromosome: on each chromosome, we take 10LOD10^{LOD} for the partitions and rescale them to sum to 1.

The threshold argument is applied to the last column (the maximum LOD score across partitions).

Value

An object of class summary.scanPhyloQTL, to be printed by print.summary.scanPhyloQTL.

Author(s)

Karl W Broman, [email protected]

References

Broman, K. W., Kim, S., An\'e, C. and Payseur, B. A. Mapping quantitative trait loci to a phylogenetic tree. In preparation.

See Also

scanPhyloQTL, plot.scanPhyloQTL, max.scanPhyloQTL, summary.scanone, inferredpartitions, simPhyloQTL

Examples

## Not run: 
# example map; drop X chromosome
data(map10)
map10 <- map10[1:19]

# simulate data
x <- simPhyloQTL(4, partition="AB|CD", crosses=c("AB", "AC", "AD"),
                 map=map10, n.ind=150,
                 model=c(1, 50, 0.5, 0))

# run calc.genoprob on each cross
x <- lapply(x, calc.genoprob, step=2)

# scan genome, at each position trying all possible partitions
out <- scanPhyloQTL(x, method="hk")

# maximum peak
max(out, format="lod")

# approximate posterior probabilities at peak
max(out, format="postprob")

# all peaks above a threshold for LOD(best) - LOD(2nd best)
summary(out, threshold=1, format="lod")

# all peaks above a threshold for LOD(best), showing approx post'r prob
summary(out, format="postprob", threshold=3)

# plot of results
plot(out)

## End(Not run)

Summarize the results of a two-dimensional genome scan

Description

Summarize the interesting aspects of the results of scantwo.

Usage

## S3 method for class 'scantwo'
summary(object, thresholds,
        what=c("best", "full", "add", "int"),
        perms, alphas, lodcolumn=1, pvalues=FALSE,
        allpairs=TRUE, ...)

Arguments

object

An object of class scantwo, the output of the function scantwo.

thresholds

A vector of length 5, giving LOD thresholds for the full, conditional-interactive, interaction, additive, and conditional-additive LOD scores. See Details, below.

what

Indicates for which LOD score the maximum should be reported. See Details, below.

perms

Optional permutation results used to derive thresholds or to calculate genome-scan-adjusted p-values. This must be consistent with the object input, in that it must have the same number of LOD score columns, though it can have just one column of permutation results, in which case they are assumed to apply to any chosen LOD score column.

alphas

If perms are included, these are the significance levels used to calculate thresholds for determining which peaks to pull out. It should be a vector of length 5, giving significance levels for the full, conditional-interactive, interaction, additive, and conditional-additive LOD scores. (It can also be a single number, in which case it is assumed that the same value is used for all five LOD scores.) If thresholds is specified, alphas should not be.

lodcolumn

If the scantwo results contain LOD scores for multiple phenotypes, this argument indicates which to use in the summary. Only one LOD score column may be considered at a time.

pvalues

If TRUE, include columns with genome-scan-adjusted p-values in the results. This requires that perms be provided.

allpairs

If TRUE, all pairs of chromosomes are considered. If FALSE, only self-self pairs are considered, so that one may more conveniently check for possible linked QTL.

...

Ignored at this point.

Details

If what="best", we calculate, for each pair of chromosomes, the maximum LOD score for the full model (two QTL plus interaction) and the maximum LOD score for the additive model. The difference between these is a LOD score for a test for interaction. We also calculate the difference between the maximum full LOD and the maximum single-QTL LOD score for the two chromosomes; this is the LOD score for a test for a second QTL, allowing for epistasis, which we call either the conditional-interactive or "fv1" LOD score. Finally, we calculate the difference between the maximum additive LOD score and the maximum single-QTL LOD score for the two chromosomes; this is the LOD score for a test for a second QTL, assuming that the two QTL act additively, which we call either the conditional-additive or "av1" LOD score. Note that the maximum full LOD and additive LOD are allowed to occur in different places.

If what="full", we find the maximum full LOD and extract the additive LOD at the corresponding pair of positions; we derive the other three LOD scores for that fixed pair of positions.

If what="add", we find the maximum additive LOD and extract the full LOD at the corresponding pair of positions; we derive the other three LOD scores for that fixed pair of positions.

If what="int", we find the pair of positions for which the difference between the full and additive LOD scores is largest, and then calculate the five LOD scores at that pair of positions.

If thresholds or alphas is provided (and note that when alphas is provided, perms must also), we extract just those pairs of chromosomes for which either (a) the full LOD score exceeds its thresholds and either the conditional-interactive LOD or the interaction LOD exceed their threshold, or (b) the additive LOD score exceeds its threshold and the conditional-additive LOD exceeds its threshold. The thresholds or alphas must be given in the order full, cond-int, int, add, cond-add.

Thresholds may be obtained by a permutation test with scantwo, but these are extremely time-consuming. For a mouse backcross, we suggest the thresholds (6.0, 4.7, 4.4, 4.7, 2.6) for the full, conditional-interactive, interaction, additive, and conditional-additive LOD scores, respectively. For a mouse intercross, we suggest the thresholds (9.1, 7.1, 6.3, 6.3, 3.3) for the full, conditional-interactive, interaction, additive, and conditional-additive LOD scores, respectively. These were obtained by 10,000 simulations of crosses with 250 individuals, markers at a 10 cM spacing, and analysis by Haley-Knott regression.

Value

An object of class summary.scantwo, to be printed by print.summary.scantwo;

Output of addpair

Note that, for output from addpair in which the new loci are indicated explicitly in the formula, the summary provided by summary.scantwo is somewhat special.

All arguments except allpairs and thresholds (and, of course, the input object) are ignored.

If the formula is symmetric in the two new QTL, the output has just two LOD score columns: lod.2v0 comparing the full model to the model with neither of the new QTL, and lod.2v1 comparing the full model to the model with just one new QTL.

If the formula is not symmetric in the two new QTL, the output has three LOD score columns: lod.2v0 comparing the full model to the model with neither of the new QTL, lod.2v1b comparing the full model to the model in which the first of the new QTL is omitted, and lod.2v1a comparing the full model to the model with the second of the new QTL omitted.

The thresholds argument should have length 1 or 2, rather than the usual 5. Rows will be retained if lod.2v0 is greater than thresholds[1] and lod.2v1 (or either of lod.2v1a or lod.2v1b) is greater than thresholds[2]. (If a single thresholds is given, we assume that thresholds[2]==0.)

The older version

The previous version of this function is still available, though it is now named summaryScantwoOld.

We much prefer the revised function. However, while we are confident that this function (and the permutations in scantwo) are calculating the relevant statistics, the appropriate significance levels for these relatively complex series of statistical tests is not yet completely clear.

Author(s)

Karl W Broman, [email protected]

See Also

scantwo, plot.scantwo, max.scantwo, condense.scantwo

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=5)
out.2dim <- scantwo(fake.f2, method="hk")

# All pairs of chromosomes
summary(out.2dim)

# Chromosome pairs meeting specified criteria
summary(out.2dim, thresholds=c(9.1, 7.1, 6.3, 6.3, 3.3))

# Similar, but ignoring the interaction LOD score in the rule
summary(out.2dim, thresholds=c(9.1, 7.1, Inf, 6.3, 3.3))

# Pairs having largest interaction LOD score, if it's > 4
summary(out.2dim, thresholds=c(0, Inf, 4, Inf, Inf), what="int")

# permutation test to get thresholds; run in two batches
#     and then combined with c.scantwoperm
## Not run: operm.2dimA <- scantwo(fake.f2, method="hk", n.perm=500)
operm.2dimB <- scantwo(fake.f2, method="hk", n.perm=500)
operm.2dim <- c(operm.2dimA, operm.2dimB)
## End(Not run)


# estimated LOD thresholds
summary(operm.2dim)

# Summary, citing significance levels and so estimating thresholds
#     from the permutation results
summary(out.2dim, perms=operm.2dim, alpha=rep(0.05, 5))

# Similar, but ignoring the interaction LOD score in the rule
summary(out.2dim, perms=operm.2dim, alpha=c(0.05, 0.05, 0, 0.05, 0.05))

# Similar, but also getting genome-scan-adjusted p-values
summary(out.2dim, perms=operm.2dim, alpha=c(0.05, 0.05, 0, 0.05, 0.05),
        pvalues=TRUE)

LOD thresholds from scantwo permutation results

Description

Print the estimated genome-wide LOD thresholds on the basis of permutation results from scantwo (with n.perm > 0).

Usage

## S3 method for class 'scantwoperm'
summary(object, alpha=c(0.05, 0.10), ...)

Arguments

object

Output from the function scantwo with n.perm > 0.

alpha

Genome-wide significance levels.

...

Ignored at this point.

Details

We take the 1α1-\alpha quantiles of the individual LOD scores.

In the case of X-chr-specific permutations, we use the combined length of the autosomes, LAL_A, and the length of the X chromosome, LXL_X, and calculate the area of the A:A, A:X, and X:X regions as LA2/2L_A^2/2, LALXL_A L_X, and LX2/2L_X^2/2, and then use the nominal significance levels of 1(1α)p1 - (1-\alpha)^p, where pp is the proportional area for that region.

Value

An object of class summary.scantwoperm, to be printed by print.summary.scantwoperm.

Author(s)

Karl W Broman, [email protected]

References

Churchill, G. A. and Doerge, R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.

See Also

scantwo, summary.scantwo, plot.scantwoperm

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=0)

## Not run: operm <- scantwo(fake.f2, n.perm=100, method="hk")
summary(operm)

Print summary of a genetic map

Description

Print summary information about a map object.

Usage

## S3 method for class 'map'
summary(object, ...)
summaryMap(object, ...)

Arguments

object

An object of class map, which is a list of vectors (or, for a sex-specific map, 2-row matrices), each specifying the locations of the markers. The object can also be of class cross, in which case the function pull.map is used to extract the genetic map from the object.

...

Ignored at this point.

Value

An object of class summary.map, which is just a data.frame containing the number of markers, length, the average inter-marker spacing, and the maximum distance between markers, for each chromosome and overall. An attribute sexsp indicates whether the map was sex-specific.

Author(s)

Karl W Broman, [email protected]

See Also

chrlen, pull.map, summary.cross

Examples

data(map10)
summary(map10)

Summarize the results of a two-dimensional genome scan

Description

Summarize the interesting aspects of the results of scantwo; this is the version of summary.scantwo that was included in R/qtl version 1.03 and earlier.

Usage

summaryScantwoOld(object, thresholds = c(0, 0, 0), lodcolumn=1,
                type = c("joint","interaction"), ...)

Arguments

object

An object of class scantwo, the output of the function scantwo.

thresholds

A vector of length three, giving LOD thresholds for the joint LOD, interaction LOD and single-QTL conditional LOD. Negative threshold values are taken relative to the maximum joint, interaction, or individual QTL LOD, respectively.

lodcolumn

If the scantwo results contain LOD scores for multiple phenotypes, this argument indicates which to use in the summary.

type

Indicates whether to pick peaks with maximal joint or interaction LOD.

...

Ignored at this point.

Details

For each pair of chromosomes, the pair of loci for which the LOD score (either joint or interaction LOD, according to the argument type) is a maximum is considered. The pair is printed only if its joint LOD score exceeds the joint threshold and either (a) the interaction LOD score exceeds its threshold or (b) both of the loci have conditional LOD scores that are above the conditional LOD threshold, where the conditional LOD score for locus q1q_1, LOD(q1q2)LOD(q_1 | q_2), is the log10\log_{10} likelihood ratio comparing the model with q1q_1 and q2q_2 acting additively to the model with q2q_2 alone.

In the case the results of scanone are not available, the maximum locus pair for each chromosome is printed whenever its joint LOD exceeds the joint LOD threshold.

The criterion used in this summary is due to Gary Churchill and Śaunak Sen, and deserves careful consideration and possible revision.

Value

An object of class summary.scantwo.old, to be printed by print.summary.scantwo.old. Pairs of loci meeting the specified criteria are printed, with their joint LOD, interaction LOD, and the conditional LOD for each locus, along with single-point P-values calculated by the χ2\chi^2 approximation. P-values are printed as log10(P)-\log_{10}(P).

If the input scantwo object does not include the results of scanone, the interaction and conditional LOD thresholds are ignored, and all pairs of loci for which the joint LOD exceeds its threshold are printed, though without their conditional LOD scores.

Author(s)

Hao Wu; Karl W Broman, [email protected]; Brian Yandell

See Also

summary.scantwo, scantwo, plot.scantwo, max.scantwo

Examples

data(fake.f2)

fake.f2 <- calc.genoprob(fake.f2, step=5)
out.2dim <- scantwo(fake.f2, method="hk")

# All pairs of loci
summaryScantwoOld(out.2dim)

# Pairs meeting specified criteria
summaryScantwoOld(out.2dim, c(7, 3, 3))

# Pairs with both conditional LODs > 2
summaryScantwoOld(out.2dim,c(0,1000,2))

# Pairs with interaction LOD is above 3
summaryScantwoOld(out.2dim,c(0,3,1000))

Switch the order of markers on a chromosome

Description

Switch the order of markers on a specified chromosome to a specified new order.

Usage

switch.order(cross, chr, order, error.prob=0.0001,
                    map.function=c("haldane","kosambi","c-f","morgan"),
                    maxit=4000, tol=1e-6, sex.sp=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

The chromosome for which the marker order is to be switched. Only one chromosome is allowed. (This should be a character string referring to the chromosomes by name.)

order

A vector of numeric indices defining the new marker order. The vector may have length two more than the number of markers, for easy in use with the output of the function ripple.

error.prob

Assumed genotyping error rate (passed to est.map).

map.function

Map function to be used (passed to est.map).

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

Value

The input cross object, but with the marker order on the specified chromosome updated, and with any derived data removed (except for recombination fractions, if present, which are not removed); the genetic map for the relevant chromosome is re-estimated.

Author(s)

Karl W Broman, [email protected]

See Also

flip.order, ripple, clean.cross

Examples

data(fake.f2)
fake.f2 <- switch.order(fake.f2, 1, c(1,3,2,4:7))

Switch alleles at selected markers

Description

Switch alleles at selected markers in a cross object.

Usage

switchAlleles(cross, markers, switch=c("AB", "CD", "ABCD", "parents"))

Arguments

cross

An object of class cross. See read.cross for details.

markers

Names of markers whose alleles are to be switched.

switch

For a 4-way cross, indicates how to switch the alleles (A for B, C for D, both A for B and C for D), or both A for C and B for D (parents).

Details

For a backcross, we exchange homozygotes (AA) and heterozygotes (AB).

For doubled haploids and recombinant inbred lines, we exchange the two homozygotes.

For an intercross, we exchange the two homozygotes, and exchange C (i.e., not AA) and D (i.e., not BB). (The heterozygotes in an intercross are left unchanged.)

For a 4-way cross, we consider the argument switch, and the exchanges among the genotypes are more complicated.

Value

The input cross object, with alleles at selected markers switched.

Author(s)

Karl W Broman, [email protected]

See Also

checkAlleles, est.rf, geno.crosstab

Examples

data(fake.f2)
geno.crosstab(fake.f2, "D5M391", "D5M81")

# switch homozygotes at marker D5M391
fake.f2 <- switchAlleles(fake.f2, "D5M391")

geno.crosstab(fake.f2, "D5M391", "D5M81")

## Not run: fake.f2 <- est.rf(fake.f2)
checkAlleles(fake.f2)

## End(Not run)

Convert a table of marker positions to a map object.

Description

Convert a data frame with marker positions to a map object.

Usage

table2map(tab)

Arguments

tab

A data frame with two columns: chromosome and position. The row names are the marker names.

Value

A map object: a list whose components (corresponding to chromosomes) are vectors of marker positions.

Author(s)

Karl W Broman, [email protected]

See Also

map2table, pull.map, est.map

Examples

tab <- data.frame(chr=c(1,1,1,1,2,2,2,2,3,3,3,3),
                  pos=c(0,2,4,8,0,2,4,8,0,2,4,8))
rownames(tab) <- paste0("marker", 1:nrow(tab))

map <- table2map(tab)

List genotypes with large error LOD scores

Description

Prints those genotypes with error LOD scores above a specified cutoff.

Usage

top.errorlod(cross, chr, cutoff=4, msg=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

cutoff

Only those genotypes with error LOD scores above this cutoff will be listed.

msg

If TRUE, print a message if there are no apparent errors.

Value

A data.frame with 4 columns, whose rows correspond to the genotypes that are possibly in error. The four columns give the chromosome number, individual number, marker name, and error LOD score.

Author(s)

Karl W Broman, [email protected]

See Also

calc.errorlod, plotGeno, plotErrorlod

Examples

data(hyper)

# Calculate error LOD scores
hyper <- calc.errorlod(hyper,error.prob=0.01)

# Print those above a specified cutoff
top.errorlod(hyper,cutoff=4)

Determine the total number of markers

Description

Determine the total number of markers in a cross or map object.

Usage

totmar(object)

Arguments

object

An object of class cross (see read.cross for details) or map (see sim.map for details).

Value

The total number of markers in the input.

Author(s)

Karl W Broman, [email protected]

See Also

read.cross, plot.cross, summary.cross, nind, nchr, nmar, nphe

Examples

data(fake.f2)
totmar(fake.f2)
map <- pull.map(fake.f2)
totmar(map)

Transformation of the phenotypes in a cross object

Description

Transform phenotypes in a cross object; by default use a logarithmic transformation, though any function may be used.

Usage

transformPheno(cross, pheno.col=1, transf=log, ...)

Arguments

cross

An object of class cross. See read.cross for details.

pheno.col

A vector of numeric indices or character strings (indicating phenotypes by name) of phenotypes to be transformed.

transf

The function to use in the transformation.

...

Additional arguments, to be passed to transf.

Value

The input cross object with the transformed phenotypes

Author(s)

Danny Arends [email protected]

See Also

mqmscan, scanone

Examples

data(multitrait)

# Log transformation of all phenotypes
multitrait.log <- transformPheno(multitrait, pheno.col=1:nphe(multitrait))

# Square-root transformation of all phenotypes
multitrait.sqrt <- transformPheno(multitrait, pheno.col=1:nphe(multitrait),
                                  transf=sqrt)

Test all possible positions for a marker

Description

Try all possible positions for a marker, keeping all other markers fixed, and evaluate the log likelihood and estimate the chromosome length.

Usage

tryallpositions(cross, marker, chr, error.prob=0.0001,
                map.function=c("haldane","kosambi","c-f","morgan"),
                m=0, p=0, maxit=4000, tol=1e-6, sex.sp=TRUE,
                verbose=TRUE)

Arguments

cross

An object of class cross. See read.cross for details.

marker

Character string with name of the marker to move about.

chr

A vector specifying which chromosomes to test for the position of the marker. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

error.prob

Assumed genotyping error rate used in the calculation of the penetrance Pr(observed genotype | true genotype).

map.function

Indicates whether to use the Haldane, Kosambi, Carter-Falconer, or Morgan map function when converting genetic distances into recombination fractions. (Ignored if m > 0.)

m

Interference parameter for the chi-square model for interference; a non-negative integer, with m=0 corresponding to no interference. This may be used only for a backcross or intercross.

p

Proportion of chiasmata from the NI mechanism, in the Stahl model; p=0 gives a pure chi-square model. This may be used only for a backcross or intercross.

maxit

Maximum number of EM iterations to perform.

tol

Tolerance for determining convergence.

sex.sp

Indicates whether to estimate sex-specific maps; this is used only for the 4-way cross.

verbose

If TRUE, print information on progress.

Value

A data frame (actually, an object of class "scanone", so that one may use plot.scanone, summary.scanone, etc.) with each row being a possible position for the marker. The first two columns are the chromosome ID and position. The third column is a LOD score comparing the hypotheses that the marker is in that position versus the hypothesis that it is not linked to that chromosome.

In the case of a 4-way cross, with sex.sp=TRUE, there are two additional columns with the estimated female and male genetic lengths of the respective chromosome, when the marker is in that position. With sex.sp=FALSE, or for other types of crosses, there is one additional column, with the estimated genetic length of the respective chromosome, when the marker is in that position.

The row names indicate the nearest flanking markers for each interval.

Author(s)

Karl W Broman, [email protected]

See Also

droponemarker, est.map, ripple, est.rf, switch.order, movemarker

Examples

data(fake.bc)
tryallpositions(fake.bc, "D7M301", 7, error.prob=0, verbose=FALSE)

Maximum distance between genotyped markers

Description

Calculates, for each individual on each chromosome, the maximum distance between genotyped markers.

Usage

typingGap(cross, chr, terminal=FALSE)

Arguments

cross

An object of class cross. See read.cross for details.

chr

Optional vector indicating the chromosomes to consider. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

terminal

If TRUE, just look at terminal typing gaps (from the terminal markers to the first typed marker).

Details

We consider not just the distances between internal genotypes, but also distances from the beginning of the chromosome to the first typed marker, and similarly for the end of the chromosome. (The start and end of a chromosome are taken to be the locations of the initial and final markers.) If terminal=TRUE, we look only at those beginning and end distances.

Value

A matrix with rows corresponding to individuals and columns corresponding to chromosomes. (If there is just one chromosome, it is a numeric vector rather than a matrix.)

Author(s)

Karl W Broman, [email protected]

See Also

ntyped, nmissing, locateXO

Examples

data(hyper)
plot(typingGap(hyper, chr=5),
     ylab="Maximum gap between typed markers (cM)",
     ylim=c(0, diff(range(pull.map(hyper,chr=5)[[1]]))))

plot(typingGap(hyper, chr=4),
     ylab="Maximum gap between typed markers (cM)",
     ylim=c(0, diff(range(pull.map(hyper,chr=4)[[1]]))))

plot(typingGap(hyper, chr=4, terminal=TRUE),
     ylab="Maximum gap between chr end and typed marker (cM)",
     ylim=c(0, diff(range(pull.map(hyper,chr=4)[[1]]))))

Write data for a QTL experiment to a file

Description

Data for a QTL experiment is written to a file (or files).

Usage

write.cross(cross, format=c("csv", "csvr", "csvs", "csvsr",
                            "mm", "qtlcart", "gary", "qtab",
                            "mapqtl", "tidy"),
            filestem="data", chr, digits=NULL, descr)

Arguments

cross

An object of class cross. See read.cross for details.

format

Specifies whether to write the data in comma-delimited, rotated comma-delimited, Mapmaker, QTL Cartographer, Gary Churchill's, QTAB, MapQTL format.

filestem

A character string giving the first part of the output file names (the bit before the dot). In Windows, use forward slashes ("/") or double backslashes ("\\") to specify directory trees.

chr

A vector specifying for which chromosomes genotype data should be written. This should be a vector of character strings referring to chromosomes by name; numeric values are converted to strings. Refer to chromosomes with a preceding - to have all chromosomes but those considered. A logical (TRUE/FALSE) vector may also be used.

digits

Number of digits to which phenotype values and genetic map positions should be rounded. If NULL (the default), they are not rounded.

descr

Character string description; used only with format="qtab".

Details

Comma-delimited formats: a single csv file is created in the formats "csv" or "csvr". Two files are created (one for the genotype data and one for the phenotype data) for the formats "csvs" and "csvsr"; if filestem="file", the two files will be names "file_gen.csv" and "file_phe.csv". See the help file for read.cross for details on these formats.

Mapmaker format: Data is written to two files. Suppose filestem="file". Then "file.raw" will contain the genotype and phenotype data, and "file.prep" will contain the necessary code for defining the chromosome assignments, marker order, and inter-marker distances.

QTL Cartographer format: Data is written to two files. Suppose filestem="file". Then "file.cro" will contain the genotype and phenotype data, and "file.map" will contain the genetic map information. Note that cross types are converted to QTL Cartographer cross types as follows: riself to RF1, risib to RF2, bc to B1 and f2 to RF2.

Gary's format: Data is written to six files. They are:
"geno.data" - genotype data;
"pheno.data" - phenotype data;
"chrid.dat" - the chromosome identifier for each marker;
"mnames.txt" - the marker names;
"markerpos.txt" - the marker positions;
"pnames.txt" - the phenotype names

QTAB format: See documentation.

MapQTL format: See documentation.

Tidy format: Data is written to three files, "stem_gen.csv", "stem_phe.csv", and "stem_map.csv" (where stem is taken from the filestem argument.

Author(s)

Karl W Broman, [email protected]; Hao Wu; Brian S. Yandell; Danny Arends; Aaron Wolen

See Also

read.cross

Examples

## Not run: data(fake.bc)

# comma-delimited format
write.cross(fake.bc, "csv", "Data/fakebc", c(1,5,13))

# rotated comma-delimited format
write.cross(fake.bc, "csvr", "Data/fakebc", c(1,5,13))

# split comma-delimited format
write.cross(fake.bc, "csvs", "Data/fakebc", c(1,5,13))

# split and rotated comma-delimited format
write.cross(fake.bc, "csvsr", "Data/fakebc", c(1,5,13))

# Mapmaker format
write.cross(fake.bc, "mm", "Data/fakebc", c(1,5,13))

# QTL Cartographer format
write.cross(fake.bc, "qtlcart", "Data/fakebc", c(1,5,13))

# Gary's format
write.cross(fake.bc, "gary", c(1,5,13))
## End(Not run)

Get x-axis locations in scanone plot

Description

Get x-axis locations for given cM positions on given chromosomes in a plot from plot.scanone)

Usage

xaxisloc.scanone(out, thechr, thepos, chr, gap=25)

Arguments

out

An object of class "scanone", as output by scanone. This must be identical to what was used in the call to plot.scanone.

thechr

Chromosome IDs at which x-axis locations are to be determined.

thepos

Chromosome positions at which x-axis locations are to be determined.

chr

Optional vector specifying which chromosomes were plotted. This must be identical to what was used in the call to plot.scanone.

gap

Gap separating chromosomes (in cM). This must be identical to what was used in the call to plot.scanone.

Details

This function allows you to identify the x-axis locations in a plot of genome scan results, produced by plot.scanone. This is useful for adding annotations, such as text or arrows.

The arguments out, chr, and gap must match what was used in the call to plot.scanone.

The arguments thechr and thepos indicate the genomic positions for which x-axis locations are desired. If they both have length > 1, they must have the same length. If one has length > 1 and one has length 1, the one with length 1 is expanded to match.

Value

A numeric vector of x-axis locations.

Author(s)

Karl W Broman, [email protected]

See Also

plot.scanone, add.threshold

Examples

data(hyper)

hyper <- calc.genoprob(hyper)
out <- scanone(hyper, method="hk")
plot(out, chr=c(1, 4, 6, 15))

# add arrow and text to indicate peak LOD score
mxout <- max(out)
x <- xaxisloc.scanone(out, mxout$chr, mxout$pos, chr=c(1,4,6,15))
arrows(x+30, mxout$lod, x+5, mxout$lod, len=0.1, col="blue")
text(x+35, mxout$lod, "the peak", col="blue", adj=c(0, 0.5))