The role of mutation rate variation and genetic diversity in the architecture of human disease

Chen Eyre-Walker, Ying and Eyre-Walker, Adam (2014) The role of mutation rate variation and genetic diversity in the architecture of human disease. PLoS ONE, 9. e90166. ISSN 1932-6203

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Evolution, Behaviour and Environment
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Depositing User: Adam Eyre-Walker
Date Deposited: 02 Mar 2014 12:16
Last Modified: 12 Mar 2017 06:49
URI: http://sro.sussex.ac.uk/id/eprint/47655

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