An evolutionary framework for common diseases: the ancestral-susceptibility model

Trends Genet. 2005 Nov;21(11):596-601. doi: 10.1016/j.tig.2005.08.007. Epub 2005 Sep 8.

Abstract

Unlike rare mendelian diseases, which are due to new mutations (i.e. derived alleles), several alleles that increase the risk to common diseases are ancestral. Moreover, population genetics studies suggest that some derived alleles that protect against common diseases became advantageous recently. These observations can be explained within an evolutionary framework in which ancestral alleles reflect ancient adaptations to the lifestyle of ancient human populations, whereas the derived alleles were deleterious. However, with the shift in environment and lifestyle, the ancestral alleles now increase the risk of common diseases in modern populations. In this article, we develop an explicit evolutionary model and use population genetics simulations to investigate the expected haplotype structure and type of disease-association signals of ancestral risk alleles.

Publication types

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

MeSH terms

  • Alleles
  • Evolution, Molecular*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genetics, Population*
  • Humans
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide