title: The role of mutation rate variation and genetic diversity in the architecture of human disease.
abstract: BACKGROUND
  We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified.
  
  
  RESULTS
  Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless.
  
  
  CONCLUSIONS
  Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease.
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, United Kingdom.
authors.forename: Ying Chen
authors.initials: YC
authors.lastname: Eyre-Walker
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Eyre-Walker
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005796:Genes; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D059645:Mutation Rate; D020641:Polymorphism, Single Nucleotide