Simultaneous fine mapping of closely linked epistatic quantitative trait loci using combined linkage disequilibrium and linkage with a general pedigreeSang Hong Lee and Julius H.J. van der Werf
The Institute for Genetics and Bioinformatics, School of Rural Science and Agriculture, University of New England, Armidale, NSW 2351, Australia
(Received 21 June 2007; accepted 21 September 2007 ; published online 10 April 2008)
Abstract - Causal mutations and their intra- and inter-locus interactions play a critical role in complex trait variation. It is often not easy to detect epistatic quantitative trait loci (QTL) due to complicated population structure requirements for detecting epistatic effects in linkage analysis studies and due to main effects often being hidden by interaction effects. Mapping their positions is even harder when they are closely linked. The data structure requirement may be overcome when information on linkage disequilibrium is used. We present an approach using a mixed linear model nested in an empirical Bayesian approach, which simultaneously takes into account additive, dominance and epistatic effects due to multiple QTL. The covariance structure used in the mixed linear model is based on combined linkage disequilibrium and linkage information. In a simulation study where there are complex epistatic interactions between QTL, it is possible to simultaneously map interacting QTL into a small region using the proposed approach. The estimated variance components are accurate and less biased with the proposed approach compared with traditional models.
Key words: fine-mapping / multiple QTL / epistasis / dominance / reversible jump MCMC
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© INRA, EDP Sciences 2008