QTL Mapping in R - Pennsylvania State UniversityMarch 16, 2010 QTL Mapping in R 7/ 19 0 20 40 60 80...

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QTL Mapping in R March 16, 2010

Transcript of QTL Mapping in R - Pennsylvania State UniversityMarch 16, 2010 QTL Mapping in R 7/ 19 0 20 40 60 80...

Page 1: QTL Mapping in R - Pennsylvania State UniversityMarch 16, 2010 QTL Mapping in R 7/ 19 0 20 40 60 80 100 0.0 0.5 1.0 1.5 2.0 Covariates chosen near the QTLs Map position (cM) lod Ghost

QTL Mapping in R

March 16, 2010

Page 2: QTL Mapping in R - Pennsylvania State UniversityMarch 16, 2010 QTL Mapping in R 7/ 19 0 20 40 60 80 100 0.0 0.5 1.0 1.5 2.0 Covariates chosen near the QTLs Map position (cM) lod Ghost

Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

R qtl

library(qtl)

R Library: qtl

sim.map: constructs a genetic map

sim.cross: simulates marker, QTL, and phenotype data

calc.genoprob: calculates conditional probabilities

scanone: produces a QTL map OR performs permutation tests

summary.scanone: identify QTLs and calculatie permutation thresholds

add.threshold: adds a permutation threshold to QTL plot

cim: performs composite interval mapping

find.marker: finds a marker near a specified position

pull.geno: extracts genotype data from a given marker

The residual phenotypic variation is normally distributed with variance 1.QTL effect: difference between the homozygote and the heterozygote

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

Ghost QTL

set.seed(1)

n<-200

map<-sim.map(len=100,n.mar=21,include.x=FALSE,eq.spacing=TRUE)

cross<-sim.cross(map,model = rbind(c(1,22,1),c(1,73,1)), type="bc",n.ind=n)

crossB<-calc.genoprob(cross,step=1)

est<-scanone(crossB)

plot(est,lwd=4,main="Simulated Backcross")

perm1<-scanone(crossB,chr=1,n.perm=500)

thresh<-summary(perm1,alpha=.05)[1]

thresh

add.threshold(est,perm=perm1,col="orange",lwd=4)

abline(v=22,col="magenta",lwd=4)

abline(v=73,col="magenta",lwd=4)

[1] 1.822760

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

Ghost QTL

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

Ghost QTL

est.cim.10 <- cim(crossB, n.marcovar=4, window=10)

est.cim.20 <- cim(crossB, n.marcovar=4, window=20)

plot(est,est.cim.10,est.cim.20,col=c("black","red","blue"),lwd=3,lty=1:3)

add.threshold(est,perm=perm1,col="orange",lwd=4)

abline(v=22,col="magenta",lwd=4)

abline(v=73,col="magenta",lwd=4)

axis(1,at=22,line=-1)

axis(1,at=73,line=-1)

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Map position (cM)

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Page 7: QTL Mapping in R - Pennsylvania State UniversityMarch 16, 2010 QTL Mapping in R 7/ 19 0 20 40 60 80 100 0.0 0.5 1.0 1.5 2.0 Covariates chosen near the QTLs Map position (cM) lod Ghost

Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

Why we need the window

mar1<- find.marker(crossB,1,22)

mar2<- find.marker(crossB,1,73)

g1<-pull.geno(crossB)[,mar1]

g2<-pull.geno(crossB)[,mar2]

est2<-scanone(crossB, addcovar=cbind(g1,g2))

plot(est2,lwd=3,main="Covariates chosen near the QTLs")

add.threshold(est2,perm=perm1,col="orange",lwd=3)

abline(v=22,col="magenta",lwd=4)

abline(v=73,col="magenta",lwd=4)

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Page 8: QTL Mapping in R - Pennsylvania State UniversityMarch 16, 2010 QTL Mapping in R 7/ 19 0 20 40 60 80 100 0.0 0.5 1.0 1.5 2.0 Covariates chosen near the QTLs Map position (cM) lod Ghost

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Map position (cM)

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

The Dataset hyper

data(hyper)

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

[1] 250

[1] 2

[1] 20

[1] 174

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 X

22 8 6 20 14 11 7 6 5 5 14 5 5 5 11 6 12 4 4 4

summary(hyper)

Backcross

No. individuals: 250

No. phenotypes: 2

Percent phenotyped: 100 100

No. chromosomes: 20

Autosomes: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

X chr: X

Total markers: 174

No. markers: 22 8 6 20 14 11 7 6 5 5 14 5 5 5 11 6 12 4 4 4

Percent genotyped: 47.7

Genotypes (%): BB:50.2 BA:49.8March 16, 2010 QTL Mapping in R 9 / 19

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot(hyper)

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Markers

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Missing genotypes

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Genetic map

bp

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female male

sex

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot.missing(hyper, reorder=TRUE)

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Missing genotypes

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

More Commands

plot(hyper)

plot.missing(hyper)

plot.map(hyper)

plot.pheno(hyper, pheno.col=1)

plot.map(hyper, chr=c(1, 4, 6, 7, 15), show.marker.names=TRUE)

plot.missing(hyper, reorder=TRUE)

hyper <- drop.nullmarkers(hyper)

totmar(hyper)

hyper <- est.rf(hyper)

newmap <- est.map(hyper, error.prob=0.01)

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot.rf(hyper)

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Pairwise recombination fractions and LOD scores

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot.map(hyper, newmap)

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Comparison of genetic maps

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

More Commands

hyper <- replace.map(hyper, newmap)

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

top.errorlod(hyper)

chr id marker errorlod

1 16 50 D16Mit171 15.999625

2 16 54 D16Mit171 15.999625

3 16 81 D16Mit5 8.914991

4 16 24 D16Mit5 8.914991

5 16 71 D16Mit5 8.914991

6 16 34 D16Mit5 8.914991

7 13 42 D13Mit78 7.999967

8 13 42 D13Mit148 7.880965

9 16 50 D16Mit5 4.914965

10 16 54 D16Mit5 4.914965

id<-top.errorlod(hyper)$id

plot.info(hyper,chr=c(1,4))

info <- plot.info(hyper)

summary(info)

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot.geno(hyper, chr=16, ind=id)

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Location (cM)

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot.info(hyper)

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

plot.info(hyper,chr=13)

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Ghost QTL Composite Interval Mapping Mouse Hypertension Plant Data

Importing Data

mydata <- read.cross("csv",

"/Users/berg/Documents/courses/phs 516/slides/lecture 6",

"plantdata.csv",genotypes=c("A","H"))

summary(mydata)

Backcross

No. individuals: 200

No. phenotypes: 28

Percent phenotyped: 100 100 100 100 100 100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100 100 100 100 100 100

No. chromosomes: 11

Autosomes: 1 2 3 4 5 6 7 8 9 10 11

Total markers: 231

No. markers: 21 21 21 21 21 21 21 21 21 21 21

Percent genotyped: 100

Genotypes (%): AA:49.7 AB:50.3

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