Linkage Disequilibrium and the Mapping of Human Disease Genes

Abstract

The potential value of haplotypes defined by several single nucleotide polymorphisms has attracted recent interest. With sufficient linkage disequilibrium (LD), haplotypes could be used in association studies to map common alleles that might influence the susceptibility to common diseases, as well as for reconstructing the evolution of the genome. It has been proposed that a globally useful resource need only be based on high frequency variants, identified from a few modest samples. Rapid progress has been made in quantifying the pattern of human LD and haplotypes defined by such common variants within and among populations. However, the quality and utility of the proposed LD-based resource could be seriously compromised if important sampling and analytical factors are overlooked in its design. The LD map should be based on adequately justified criteria defined by sound population genetic principles.