Exploring haplotype sharing methods in general and isolated populations todetect gene(s) of a complex genetic trait

We applied a new haplotype sharing method to the simulated Genetic Analysis Workshop 12 data for both isolated and general populations without knowled ge of the disease model, using affection status as phenotype and three diff erent sample sizes. The highest peak for the mean sharing of the haplotypes was found in the isolated population for the markers D06G034 and D06G035, which flank the candidate genes located on chromosome 6, with -log(10)(p) v alues of 2.9 and 7.0 in the moderate and large study samples, respectively. The whole genome screen detected three further loci with -log(10)(p) value s of 3.0, which turned out to be false positives. None of the true gene loc i were detected in the general population even in the largest sample. The t est of linkage disequilibrium based on excess haplotype sharing over the li nkage equilibrium expectation revealed z-values one order of magnitude high er in the isolated than in the general population. This approach appears to be promising for mapping genes of complex diseases depending on population characteristics. (C) 2001 Wiley-Liss, Inc.