The role of mutation rate variation and genetic diversity in the architecture of human disease
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...
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Published in | PloS one Vol. 9; no. 2; p. e90166 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
27.02.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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, 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.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: YEW AEW. Performed the experiments: YEW AEW. Analyzed the data: YEW AEW. Contributed reagents/materials/analysis tools: YEW AEW. Wrote the paper: YEW AEW. Competing Interests: The authors have declared that no competing interests exist. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0090166 |