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

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posted on 2023-06-08, 16:48 authored by Ying ChenYing Chen, Adam Eyre-WalkerAdam Eyre-Walker
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

PLoS ONE

ISSN

1932-6203

Publisher

Public Library of Science

Volume

9

Article number

e90166

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2014-03-02

First Open Access (FOA) Date

2014-03-02

First Compliant Deposit (FCD) Date

2014-02-28

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