Shaking the tree: mapping complex disease genes with linkage disequilibrium

Lancet. 2005 Oct 1;366(9492):1223-34. doi: 10.1016/S0140-6736(05)67485-5.


Much effort and expense are being spent internationally to detect genetic polymorphisms contributing to susceptibility to complex human disease. Concomitantly, the technology for detecting and genotyping single nucleotide polymorphisms (SNPs) has undergone rapid development, yielding extensive catalogues of these polymorphisms across the genome. Population-based maps of the correlations amongst SNPs (linkage disequilibrium) are now being developed to accelerate the discovery of genes for complex human diseases. These genomic advances coincide with an increasing recognition of the importance of very large sample sizes for studying genetic effects. Together, these new genetic and epidemiological data hold renewed promise for the identification of susceptibility genes for complex traits. We review the state of knowledge about the structure of the human genome as related to SNPs and linkage disequilibrium, discuss the potential applications of this knowledge to mapping complex disease genes, and consider the issues facing whole genome association scanning using SNPs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping*
  • Gene Frequency
  • Genetics, Population
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium*
  • Polymorphism, Single Nucleotide