We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10–30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations. The International HapMap Consortium has produced a second-generation version of its remarkable haplotype map of the human genome. The Phase II HapMap charts human genetic variation even more extensively than the original, tripling of the number of genetic markers included. The original HapMap was instrumental in making large-scale genome-wide association studies possible. An indication of how this type of work will be extended with 'HapMap2' is presented in this issue: Sabeti et al. build on previous work detecting signs of positive natural selection on human genes. With many more markers now available, they have discovered three examples of apparent population-specific selection based on geographic area — involving gene pairs linked to Lassa virus in West Africa, skin pigmentation in Europe and hair follicle development in Asia — and they speculate on how these may relate to human biology. A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

A second generation human haplotype map of over 3.1 million SNPs