A second generation human haplotype map of over 3.1 million SNPs

Abstract

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.

Significant lethality following liver resection in A20 heterozygous knockout mice uncovers a key role for A20 in liver regeneration

“…For instance, the percentage of homozygous carriers of rs610604 minor allele (prevalent in patients with psoriasis and predicting higher coronary artery disease in diabetic patients) reaches 18% in Europeans and 32-50% in Africans, while the percentage of homozygous carriers of rs661561minor allele (associated with Grave's disease) reaches 37% in Europeans and up to 50% in Asians. 60,61 However, and beyond the use of A20 SNPs as predictive marker of LR, our results mostly reinforce our pursuit of A20-based therapies to promote LR and improve safety of extensive LR for donation or tumor.…”

Investigation of DNA polymorphisms in SMAD genes for genetic predisposition to diabetic nephropathy in patients with type 1 diabetes mellitus

“…cam.ac.uk/clayton/software/stata, accessed 8 August 2008). With the release of Phase II of the International HapMap Project [9], selection of tag SNPs became a cost-effective option. Sample-based genotypes (data release number 20) were downloaded for all variants in genetic regions surrounding SMAD1, SMAD4 and SMAD5.…”

MHC‐dependent mate choice in humans: Why genomic patterns from the HapMap European American dataset support the hypothesis

“…They were originally produced for medical genetics purposes but offer a great opportunity to study the evolutionary forces shaping our genome [20]. So far, two studies have used the HapMap datasets to re-evaluate the role of MHC in human mate choice [21,22].…”