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Mapping Populations
QTL Mapping
Objective is to identify QTLs that affect
the quantitative trait of interest.
Methods to Detect QTLS
Data Needed for QTL Mapping
y = µ + MG i + e
Sample Data
Input files • cvs format
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Sample Data Sample Data
• Map maker format – genotype data • Map maker format – phenotype data
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plot.missing()
Data Quality Check
• Plot a grid showing
which genotypes
are missing
plot() est.rf()
• Estimate the sex-averaged recombination
• Plots all graphs fraction between all pairs of genetic
together markers
• For a backcross, one can simply count
recombination events. For an intercross or
4-way cross, recombination fractions must
be estimated.
Plot both rf and lod
plot.rf()
Plot rf and lod for Chr 1 only Plot lod only for Chr 2 and 3
scanone()
scanone() scanone(cross, chr, pheno.col=1,
model=c("normal","binary","2part","np"),
• Genome scan with a single QTL method=c("em","imp","hk","ehk","mr","mr-
model, with possible allowance for imp","mr-argmax"), addcovar=NULL, n.perm,)
covariates, using any of several cross – object to be analyzed
possible models for the phenotype chr - optional vector indicating the chromosomes for
and any of several possible which LOD scores should be calculated
numerical methods pheno.col – column number of the phenotype data
addcovar - additive covariates, allowed only for the normal
and binary models
forward
n.perm – the number of permutations
model=
• normal – the standard QTL model for QTL
mapping. The residual phenotypic variation
is assumed to follow a normal distribution
• binary – for binary phenotype, which must
have values 0 and 1. Available for em and mr
methods only
• 2part – when there is a spike in the
phenotype distribution
• np( non-parametric) – an extension of the
Kruskal-Wallis test is used
Single marker ANOVA
method=
• Threshold=3
• mr – single marker regression
o mr – deletes individuals with missing genotype
o mr-imp – fills in missing data using single imputation
o mr-argmax – fills in missing data suing the Vitervi algorithm
• em – maximum likelihood using the Expectation-
maximization (EM) algorithm • Using permutation test
• hk – Haley-Knott regression
• imp – multiple imputation (Sen and Churchill, 2001).
Uses Monte Carlo algorithm instead of EM.
• ehk – extended Haley-Knott method (Feenstra et al.,
2006). An improvement of the hk especially when
epistasis exists between QTLs
Estimating heritability
for each marker Interval Mapping (IM)
forward
Maximum Likelihood Maximum Likelihood
• A test statistic for this method is:
• The likelihood for a given set of parameters
(QTL position and QTL effect) given the Max_Likelihood(reduced model)
LR = −2 ln
observed data on phenotypes and marker Max_Likelihood(full model)
genotypes The reduced model refers to the null-
• The estimates for the parameters are those hypothesis of no QTL effect.
where the likelihood are highest
• Expectation-maximization(EM) method is • The LOD score for a QTL at position c is:
used in the estimation procedure LR(c) LR(c)
LOD(c) = =
2ln10 4.61
Red – EM
Blue - EHK
R/qtl
Interval Mapping
EM, HK, and EHK
calc.genoprob()
Interval mapping
• Maximum likelihood • Calculate QTL probabilities conditional
on the available marker data.
• Needed in most mapping functions
o step – indicates step size in cM at which the
probabilities are to be calculated
o error.prob – assumed genotyping error rate
Permutation test can also be used to get
threshold value for lod scores. Note: genotyping error occurs when the
observed genotype of an individual does not
correspond to the true genotype.
Combining IM results
Interval mapping
• Extended Haley-Knott Regression
blue – em
red – cim
Sample Multiple QTL Mapping
Multiple QTL Mapping output