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Title: Simultaneous Fine Mapping of Multiple Closely Linked Quantitative Trait Loci Using Combined Linkage Disequilibrium and Linkage With a General Pedigree
Contributor(s): Lee, Sang Hong  (author); Van Der Werf, JH  (author)orcid 
Publication Date: 2006
DOI: 10.1534/genetics.106.057653
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Abstract: Within a small region (e.g., <10 cM), there can be multiple quantitative trait loci (QTL) underlying phenotypes of a trait. Simultaneous fine mapping of closely linked QTL needs an efficient tool to remove confounded shade effects among QTL within such a small region. We propose a variance component method using combined linkage disequilibrium (LD) and linkage information and a reversible jump Markov chain Monte Carlo (MCMC) sampling for model selection. QTL identity-by-descent (IBD) coefficients between individuals are estimated by a hybrid MCMC combining the random walk and the meiosis Gibbs sampler. These coefficients are used in a mixed linear model and an empirical Bayesian procedure combines residual maximum likelihood (REML) to estimate QTL effects and a reversible jump MCMC that samples the number of QTL and the posterior QTL intensities across the tested region. Note that two MCMC processes are used, i.e., an (internal) MCMC for IBD estimation and an (external) MCMC for model selection. In a simulation study, the use of the multiple-QTL model clearly removes the shade effects between three closely linked QTL located at 1.125, 3.875, and 7.875 cM across the region of 10 cM, using 40 markers at 0.25-cM intervals. It is shown that the use of combined LD and linkage information gives much more useful information compared to using linkage information alone for both single- and multiple-QTL analyses. When using a lower marker density (11 markers at 1-cM intervals), the signal of the second QTL can disappear. Extreme values of past effective size (resulting in extreme levels of LD) decrease the mapping accuracy.
Publication Type: Journal Article
Source of Publication: Genetics, 173(4), p. 2329-2337
Publisher: Genetics Society of America
Place of Publication: United States of America
ISSN: 1943-2631
Fields of Research (FoR) 2008: 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics)
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article

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