MAPPING OF COMPLEX TRAITS BY SINGLE-NUCLEOTIDE POLYMORPHISMS

Molecular geneticists are developing the third-generation human genome map with single-nucleotide polymorphisms (SNPs), which can be assayed via chip-based microarrays. One use of these SNP markers is the abili ty to locate loci that may be responsible for complex traits, via link age/linkage-disequilibrium analysis. Ln this communication, we describ e a semiparametric method for combined linkage/linkage-disequilibrium analysis using SNP markers. Asymptotic results are obtained for the es timated parameters, and the finite-sample properties are evaluated via a simulation study. We also applied this technique to a simulated gen ome-scan experiment for mapping a complex trait with two major genes. This experiment shows that separate linkage and linkage-disequilibrium analyses correctly detected the signals of both major genes; but the rates of false-positive signals seem high.When linkage and linkage-dis equilibrium signals were combined, the analysis yielded much stronger and clearer signals for the presence of two major genes than did two s eparate analyses.