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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Format | Journal Article |
Language | English |
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27.02.2014
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Abstract | 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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AbstractList | 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. 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. 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. 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. BACKGROUNDWe 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. RESULTSConsistent 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. CONCLUSIONSOur 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. |
Audience | Academic |
Author | Eyre-Walker, Ying Chen Eyre-Walker, Adam |
AuthorAffiliation | School of Life Sciences, University of Sussex, Brighton, United Kingdom Georgia Institute of Technology, United States of America |
AuthorAffiliation_xml | – name: Georgia Institute of Technology, United States of America – name: School of Life Sciences, University of Sussex, Brighton, United Kingdom |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24587257$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1038_s41467_020_14284_2 crossref_primary_10_7554_eLife_69026 crossref_primary_10_1016_j_tig_2016_01_004 crossref_primary_10_2217_pgs_2020_0039 crossref_primary_10_1080_03235408_2020_1744978 |
Cites_doi | 10.1038/337283a0 10.1371/journal.pgen.1000071 10.1101/gr.106666.110 10.1038/nature11632 10.1038/nature04072 10.1101/gr.098947.109 10.1038/ng917 10.1093/molbev/msp314 10.1016/S0168-9525(02)02669-0 10.1038/nrg2526 10.1186/gb-2004-5-7-r47 10.1038/nrg3098 10.1093/genetics/134.4.1289 10.1073/pnas.0912402107 10.1016/j.cell.2012.11.019 10.1038/embor.2012.165 10.1016/j.cub.2008.04.074 10.1101/gr.3461105 10.1126/science.1222794 10.1093/nar/gkh330 10.1098/rspb.2006.3720 10.1093/genetics/156.1.297 10.1086/375657 10.1038/ng.363 10.1017/S0016672300014634 10.1002/humu.21616 10.1534/genetics.111.132654 10.1016/S0378-1119(03)00772-8 10.1186/gb-2008-9-4-r76 |
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Copyright | COPYRIGHT 2014 Public Library of Science 2014 Eyre-Walker, Eyre-Walker. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2014 Eyre-Walker, Eyre-Walker 2014 Eyre-Walker, Eyre-Walker |
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Notes | 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. |
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References | 23146897 - EMBO Rep. 2012 Dec;13(12):1123-9 16136131 - Nature. 2005 Sep 1;437(7055):69-87 8375663 - Genetics. 1993 Aug;134(4):1289-303 20103589 - Genome Res. 2010 Apr;20(4):447-57 18464896 - PLoS Genet. 2008 May;4(5):e1000071 19966280 - Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):139-44 21953857 - Hum Mutat. 2012 Jan;33(1):136-43 21954163 - Genetics. 2011 Dec;189(4):1389-402 19204717 - Nat Rev Genet. 2009 Mar;10(3):195-205 20026481 - Mol Biol Evol. 2010 May;27(5):1077-86 22955828 - Science. 2012 Sep 7;337(6099):1190-5 23128226 - Nature. 2012 Nov 1;491(7422):56-65 12127766 - Trends Genet. 2002 Jul;18(7):337-40 15020709 - Nucleic Acids Res. 2004;32(5):1731-7 2911369 - Nature. 1989 Jan 19;337(6204):283-5 18571414 - Curr Biol. 2008 Jun 24;18(12):883-9 18447906 - Genome Biol. 2008;9(4):R76 19287383 - Nat Genet. 2009 Apr;41(4):393-5 16140990 - Genome Res. 2005 Sep;15(9):1222-31 12053178 - Nat Genet. 2002 Jul;31(3):241-7 21969038 - Nat Rev Genet. 2011 Nov;12(11):756-66 17134994 - Proc Biol Sci. 2007 Jan 7;274(1606):1-10 20686123 - Genome Res. 2010 Nov;20(11):1503-11 12740762 - Am J Hum Genet. 2003 Jun;72(6):1527-35 23260136 - Cell. 2012 Dec 21;151(7):1431-42 14585509 - Gene. 2003 Oct 30;318:169-75 15239832 - Genome Biol. 2004;5(7):R47 4407212 - Genet Res. 1974 Feb;23(1):23-35 10978293 - Genetics. 2000 Sep;156(1):297-304 FA Kondrashov (ref9) 2004; 32 MJ Lercher (ref28) 2002; 18 B Charlesworth (ref6) 1993; 134 B Charlesworth (ref7) 2009; 10 ref2 L Duret (ref26) 2008; 4 H Ellegren (ref22) 2007; 274 C Park (ref23) 2012; 13 CL Chen (ref18) 2010; 20 A Hodgkinson (ref11) 2012; 33 R Blekhman (ref16) 2008; 18 NG Smith (ref8) 2003; 318 S Tyekucheva (ref24) 2008; 9 G McVicker (ref20) 2010; 20 MT Maurano (ref21) 2012; 337 I Hellmann (ref27) 2003; 72 (ref13) 2005; 437 MW Nachman (ref14) 2000; 156 KH Wolfe (ref25) 1989; 337 H Huang (ref10) 2004; 5 I Hellmann (ref3) 2005; 15 (ref15) 2012; 491 TI Gossmann (ref4) 2011; 189 A Kong (ref17) 2002; 31 JA Stamatoyannopoulos (ref30) 2009; 41 CJ Pink (ref29) 2010; 27 A Hodgkinson (ref1) 2011; 12 RS Hansen (ref19) 2010; 107 JJ Michaelson (ref12) 2012; 151 J Maynard Smith (ref5) 1974; 23 |
References_xml | – volume: 337 start-page: 283 year: 1989 ident: ref25 article-title: Mutation rates differ among regions of the mammalian genome publication-title: Nature doi: 10.1038/337283a0 contributor: fullname: KH Wolfe – volume: 4 start-page: e1000071 year: 2008 ident: ref26 article-title: The impact of recombination on nucleotide substitutions in the human genome publication-title: PLoS Genet doi: 10.1371/journal.pgen.1000071 contributor: fullname: L Duret – volume: 20 start-page: 1503 year: 2010 ident: ref20 article-title: Genomic signatures of germline gene expression publication-title: Genome research doi: 10.1101/gr.106666.110 contributor: fullname: G McVicker – volume: 491 start-page: 56 year: 2012 ident: ref15 article-title: An integrated map of genetic variation from 1,092 human genomes publication-title: Nature doi: 10.1038/nature11632 – volume: 437 start-page: 69 year: 2005 ident: ref13 article-title: Initial sequence of the chimpanzee genome and comparison with the human genome publication-title: Nature doi: 10.1038/nature04072 – volume: 20 start-page: 447 year: 2010 ident: ref18 article-title: Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes publication-title: Genome Res doi: 10.1101/gr.098947.109 contributor: fullname: CL Chen – volume: 31 start-page: 241 year: 2002 ident: ref17 article-title: A high-resolution recombination map of the human genome publication-title: Nat Genet doi: 10.1038/ng917 contributor: fullname: A Kong – volume: 27 start-page: 1077 year: 2010 ident: ref29 article-title: Timing of replication is a determinant of neutral substitution rates but does not explain slow Y chromosome evolution in rodents publication-title: Mol Biol Evol doi: 10.1093/molbev/msp314 contributor: fullname: CJ Pink – volume: 18 start-page: 337 year: 2002 ident: ref28 article-title: Human SNP variability and mutation rate are higher in regions of high recombination publication-title: Trends Genet doi: 10.1016/S0168-9525(02)02669-0 contributor: fullname: MJ Lercher – volume: 10 start-page: 195 year: 2009 ident: ref7 article-title: Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation publication-title: Nat Rev Genet doi: 10.1038/nrg2526 contributor: fullname: B Charlesworth – volume: 5 start-page: R47 year: 2004 ident: ref10 article-title: Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes publication-title: Genome biology doi: 10.1186/gb-2004-5-7-r47 contributor: fullname: H Huang – volume: 12 start-page: 756 year: 2011 ident: ref1 article-title: Variation in the mutation rate across mammalian genomes publication-title: Nature Reviews Genetics doi: 10.1038/nrg3098 contributor: fullname: A Hodgkinson – volume: 134 start-page: 1289 year: 1993 ident: ref6 article-title: The effect of deleterious mutations on neutral molecular variation publication-title: Genetics doi: 10.1093/genetics/134.4.1289 contributor: fullname: B Charlesworth – volume: 107 start-page: 139 year: 2010 ident: ref19 article-title: Sequencing newly replicated DNA reveals widespread plasticity in human replication timing publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.0912402107 contributor: fullname: RS Hansen – ident: ref2 – volume: 151 start-page: 1431 year: 2012 ident: ref12 article-title: Whole-genome sequencing in autism identifies hot spots for de novo germline mutation publication-title: Cell doi: 10.1016/j.cell.2012.11.019 contributor: fullname: JJ Michaelson – volume: 13 start-page: 1123 year: 2012 ident: ref23 article-title: Genomic evidence for elevated mutation rates in highly expressed genes publication-title: EMBO reports doi: 10.1038/embor.2012.165 contributor: fullname: C Park – volume: 18 start-page: 883 year: 2008 ident: ref16 article-title: Natural selection on genes that underlie human disease susceptibility publication-title: Curr Biol doi: 10.1016/j.cub.2008.04.074 contributor: fullname: R Blekhman – volume: 15 start-page: 1222 year: 2005 ident: ref3 article-title: Why do human diversity levels vary at a megabase scale? publication-title: Genome Res doi: 10.1101/gr.3461105 contributor: fullname: I Hellmann – volume: 337 start-page: 1190 year: 2012 ident: ref21 article-title: Systematic localization of common disease-associated variation in regulatory DNA publication-title: Science doi: 10.1126/science.1222794 contributor: fullname: MT Maurano – volume: 32 start-page: 1731 year: 2004 ident: ref9 article-title: Bioinformatical assay of human gene morbidity publication-title: Nucleic acids research doi: 10.1093/nar/gkh330 contributor: fullname: FA Kondrashov – volume: 274 start-page: 1 year: 2007 ident: ref22 article-title: Characteristics, causes and evolutionary consequences of male-biased mutation publication-title: Proc Biol Sci doi: 10.1098/rspb.2006.3720 contributor: fullname: H Ellegren – volume: 156 start-page: 297 year: 2000 ident: ref14 article-title: Estimate of the mutation rate per nucleotide in humans publication-title: Genetics doi: 10.1093/genetics/156.1.297 contributor: fullname: MW Nachman – volume: 72 start-page: 1527 year: 2003 ident: ref27 article-title: A neutral explanation for the correlation of diversity with recombination rates in humans publication-title: Am J Hum Genet doi: 10.1086/375657 contributor: fullname: I Hellmann – volume: 41 start-page: 393 year: 2009 ident: ref30 article-title: Human mutation rate associated with DNA replication timing publication-title: Nat Genet doi: 10.1038/ng.363 contributor: fullname: JA Stamatoyannopoulos – volume: 23 start-page: 23 year: 1974 ident: ref5 article-title: The hitch-hiking effect of a favourable gene publication-title: Genet Res doi: 10.1017/S0016672300014634 contributor: fullname: J Maynard Smith – volume: 33 start-page: 136 year: 2012 ident: ref11 article-title: The large scale distribution of somatic mutations in cancer genomes publication-title: Human Mutation doi: 10.1002/humu.21616 contributor: fullname: A Hodgkinson – volume: 189 start-page: 1389 year: 2011 ident: ref4 article-title: Quantifying the variation in the effective population size within a genome publication-title: Genetics doi: 10.1534/genetics.111.132654 contributor: fullname: TI Gossmann – volume: 318 start-page: 169 year: 2003 ident: ref8 article-title: Human disease genes: patterns and predictions publication-title: Gene doi: 10.1016/S0378-1119(03)00772-8 contributor: fullname: NG Smith – volume: 9 start-page: R76 year: 2008 ident: ref24 article-title: Human-macaque comparisons illuminate variation in neutral substitution rates publication-title: Genome Biol doi: 10.1186/gb-2008-9-4-r76 contributor: fullname: S Tyekucheva |
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Snippet | 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... 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... BACKGROUNDWe 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... 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... 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... |
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SubjectTerms | Analysis of Variance Animals Architecture Biology Chimpanzees Consortia Deoxyribonucleic acid Disease Divergence DNA Gene expression Genes Genetic aspects Genetic Association Studies Genetic diversity Genetic Predisposition to Disease Genetic Variation Genomes Genomics Humans Life sciences Loci Medical research Mutation Mutation Rate Mutation rates Polymorphism, Single Nucleotide Population Predictions Variation |
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Title | The role of mutation rate variation and genetic diversity in the architecture of human disease |
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