A first-generation linkage disequilibrium map of human chromosome 22

A collection of DNA sequence variants across the genome may be used to test specific genes or regions of the human genome for association with a variety of phenotypes such as disease risk or variable drug response. Detecting association relies on the non-random correlation (“linkage disequilibrium”, LD) of one of the marker alleles with a trait-related variant. We have measured LD along the complete sequence of human chromosome 22. Duplicate genotyping and analysis of 1,504 markers in CEPH reference families at a median spacing of 15kb reveals a highly variable pattern of LD along the chromosome, in which extensive regions of virtually complete LD up to 758 kb in length are interspersed with regions of little or no detectable LD. The LD patterns are replicated in 1,286 overlapping markers genotyped on a panel of unrelated U.K. Caucasians. There is a strong correlation between high LD and low recombination frequency in the extant genetic map, reflecting patterns of historic recombination between ancestral chromosomes that yield conserved blocks of LD in present-day chromosomes. This study demonstrates the feasibility for developing genome-wide maps of LD