  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. 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.
Complex disease gene are predicted to have higher rates of non-synonymous
mutation than non-disease genes, but the opposite pattern is found in Mendelian
disease 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. Our results
suggest that variation in the genic mutation rate and the genetic architecture
of the locus play a minor role in determining whether a gene is associated with
disease.
