New methods
for linkage disequilibrium fine mapping of quantitaive trait loci
Simon Boitard,
Jihad Abdallah, Brigitte Mangin, Hubert de Rochambeau, Christine Cierco
INRA, Toulouse
Linkage
disequilibrium is the non-random allelic association between different
loci. Recently, it has been advocated as a powerful tool to refine gene
location estimates, thanks to its ability to incorporate the effects of
a large number of past generations of recombination. In localizing
mendelian disease genes in human populatiions, this approach has
already been succesfull. But more research work is still needed to
determine its utility for fine mapping Quantitative Trait Loci (QTL) in
animal populations. My talk gives some new insights on this question.
I first present an interval mapping method for QTL. Following Xiong and
Guo (1997), we use a maximum likehood approach and model the joint
history of the quantitative trait locus and two flanking markers as a
stochastic process. Since we deal with QTL, we can't assume as they do
that one of the trait alleles is rare, and this brings us to derive the
expected haplotype frequencies in a slightly different way. We compare
our method with other existing ones under several simulation scenarios.
Mean square errors of the QTL location estimates are significantly
smaller than those obatined with Abdallah et al (2004)'s method, and
similar to those obtained by Meuwissen and Goddart (2000). And our
method is much faster than this last one.
Finally I propose a different way of evaluating the likehood above,
based on a diffusion approximation of the Wright Fisher model. It gives
a more precise estimate of the likehood, taking account of the
stochasticity of haplotype frequency evolution over generations. It
applies to many kinds of populations.