Linkage disequilibrium interval mapping of quantitative trait loci.
BACKGROUND
For many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed to deal with simply inherited disease traits. However, locating quantitative trait loci is statistically more challenging and considerable research is needed to provide robust and computationally efficient methods.


RESULTS
Under a three-locus Wright-Fisher model, we derived approximate expressions for the expected haplotype frequencies in a population. We considered haplotypes comprising one trait locus and two flanking markers. Using these theoretical expressions, we built a likelihood-maximization method, called HAPim, for estimating the location of a quantitative trait locus. For each postulated position, the method only requires information from the two flanking markers. Over a wide range of simulation scenarios it was found to be more accurate than a two-marker composite likelihood method. It also performed as well as identity by descent methods, whilst being valuable in a wider range of populations.


CONCLUSIONS
Our method makes efficient use of marker information, and can be valuable for fine mapping purposes. Its performance is increased if multiallelic markers are available. Several improvements can be developed to account for more complex evolution scenarios or provide robust confidence intervals for the location estimates.
Unité de Biométrie et Intelligence Artificielle, Institut National de la Recherche Agronomique, BP 52627, 31326 Castanet-Tolosan Cedex, France. simon.boitard@toulouse.inra.fr
Simon
S
Boitard
Jihad
J
Abdallah
Hubert
H
de Rochambeau
Christine
C
Cierco-Ayrolles
Brigitte
B
Mangin
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008962:Models, Theoretical; D040641:Quantitative Trait Loci
D005819:Genetic Markers