A haplotype map of the human genome

Abstract

A haplotype map of the human genomeThe International HapMap Consortium* Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Genome‐wide association studies of multiple sclerosis

“…The development of genetic maps covering much of the genome led to linkage analyses in extended MS affected families from a number of countries, primarily of European ancestry 23, 24, 25, 26, 27, 28, 29, 30, 31, 32. These validated the HLA association but showed no significant linkage to loci outside the MHC.…”

“…The completion of the human genome sequencing project led to the development of complete catalogues of common genetic variation across the genome, and concomitant technologies to assay these variants in a cost‐effective and high‐throughput manner 25, 26. This technological development enabled the profiling of thousands of samples in a single study and prompted a shift away from family studies, where samples are necessarily limited and ascertainment challenging, to population‐based association studies comparing unrelated cases and controls 27.…”

Characterizing linkage disequilibrium and evaluating imputation power of human genomic insertion-deletion polymorphisms

“…The HapMap consortium used this measurement to describe SNP tagging [29]. Surprisingly, mean max r 2 for indel-SNP was significantly higher than SNP-SNP (Figure 1) for all SNP panels at all distances ( P < 0.05, Mann-Whitney).…”

Translating Lung Function Genome-Wide Association Study (GWAS) Findings

“…The advent of genome-wide association (GWA) studies is attributable to advances in genotyping technology (Syvanen, 2005), the Human Genome Project (Venter et al, 2001) and the completion of the HapMap project (International HapMap, 2005). In GWAS, hundreds of thousands of SNPs in large populations are assayed to determine the co-occurrence of these variants with disease symptoms or with certain trait distribution (Pearson & Manolio, 2008).…”

“…In GWAS, hundreds of thousands of SNPs in large populations are assayed to determine the co-occurrence of these variants with disease symptoms or with certain trait distribution (Pearson & Manolio, 2008). Importantly these SNPs are selected to capture the maximum information on the human genome by using optimised panels that tag haplotype blocks which is made possible by our improved understanding of the human genome, thanks to the initiatives such as HapMap (International HapMap, 2005). Since GWAS is a population-based approach, most GWAS have concentrated on looking for association with common variants (>5%) and they are generally less well designed to evaluate low allele frequency variants (Hirschhorn & Daly, 2005).…”