Linkage disequilibrium in the human genome

Nature. 2001 May 10;411(6834):199-204. 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Bias
  • Chromosome Mapping / methods*
  • Computer Simulation
  • Europe / ethnology
  • Founder Effect
  • Genetic Diseases, Inborn / genetics
  • Genome, Human*
  • Haplotypes / genetics
  • Heterozygote
  • Humans
  • Linkage Disequilibrium / genetics*
  • Models, Genetic
  • Nigeria
  • Phylogeny
  • Polymorphism, Single Nucleotide / genetics*
  • Racial Groups / genetics
  • Recombination, Genetic / genetics
  • Reproducibility of Results
  • Selection, Genetic
  • Time Factors
  • United States