EVOLUTION AND GLOBAL DISTRIBUTION OF HALOTYPES

Yale University, New Haven CT

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Abstract

During the past several years linkage disequilibrium has become increasingly used as a tool in cloning disease genes, fine mapping of loci, prenatal diagnosis, disease association studies, and studies of population relationships and divergence. Yet little is known about the distribution and intensity of disequilibrium either across the genome, within a population, or across populations for a particular locus. This project will collect haplotype data and measure disequilibrium for 400 locus-population combinations--at 200 multisite loci distributed across the genome in 20 populations from around the world in order to investigate (in conjunction with Project 4 and the Scientific Core) some of the population-specific factors (effective population size, admixture, etc.) and locus-specific factors (genomic location (telomere, centromere, mid-arm) and mutation type (single base changes, short tandem repeat)) that affect linkage disequilibrium. Haplotypes at each locus will consist of at least three physically mapped polymorphisms, usually with one short tandem repeat polymorphism and two or more single nucleotide polymorphisms. Knowledge of the ancestral and derived states of the SNPs (from studies of other primates) will help define the evolutionary histories of the SNP-based haplotypes. Inclusion of the STRPs within these frameworks of SNPs will provide data informative for relative mutation rate studies. They systematic effects of recombination are deliberately minimized in this project by limiting the molecular length of the haplotypes examined to about 30 kb; the effects of population history and locus will thus be spot-lighted.