Linkage disequilibrium in the human genome

• Published in: Nature (London) Vol. 411; no. 6834; pp. 199 - 204
• Main Authors: Reich, David E, Cargill, Michele, Bolk, Stacey, Ireland, James, Sabeti, Pardis C, Richter, Daniel J, Lavery, Thomas, Kouyoumjian, Rose, Farhadian, Shelli F, Ward, Ryk, Lander, Eric S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 10.05.2001; Nature Publishing Group
• Subjects: Alleles; Bias; Biological and medical sciences; Chromosome Mapping - methods; Chromosomes; Classical genetics, quantitative genetics, hybrids; Computer Simulation; Continental Population Groups - genetics; Disease; Europe - ethnology; Experiments; Founder Effect; Fundamental and applied biological sciences. Psychology; Genetic Diseases, Inborn - genetics; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genomics; Haplotypes; Haplotypes - genetics; Heterozygote; Human; Humans; Linkage Disequilibrium - genetics; Models, Genetic; Nigeria; Phylogeny; Polymorphism, Single Nucleotide - genetics; Recombination, Genetic - genetics; Regions; Reproducibility of Results; Selection, Genetic; single nucleotide polymorphisms; Time Factors; United States; United States; North America; America; Genetic mapping; Human; Genetic marker; Linkage equilibrium; Genome
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35075590

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.