TY - JOUR
T1 - Recombination affects accumulation of damaging and disease-associated mutations in human populations
AU - Hussin, Julie G.
AU - Hodgkinson, Alan
AU - Idaghdour, Youssef
AU - Grenier, Jean Christophe
AU - Goulet, Jean Philippe
AU - Gbeha, Elias
AU - Hip-Ki, Elodie
AU - Awadalla, Philip
N1 - Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/4/28
Y1 - 2015/4/28
N2 - Many decades of theory have demonstrated that, in non-recombining systems, slightly deleterious mutations accumulate non-reversibly, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion; however, it is not clear the extent to which damaging mutations accumulate along chromosomes with highly variable rates of crossing over. Using high-coverage sequencing data from over 1,400 individuals in the 1000 Genomes and CARTaGENE projects, we show that recombination rate modulates the distribution of putatively deleterious variants across the entire human genome. Exons in regions of low recombination are significantly enriched for deleterious and disease-associated variants, a signature varying in strength across worldwide human populations with different demographic histories. Regions with low recombination rates are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effects on health, a phenomenon likely affecting disease susceptibility in humans.
AB - Many decades of theory have demonstrated that, in non-recombining systems, slightly deleterious mutations accumulate non-reversibly, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion; however, it is not clear the extent to which damaging mutations accumulate along chromosomes with highly variable rates of crossing over. Using high-coverage sequencing data from over 1,400 individuals in the 1000 Genomes and CARTaGENE projects, we show that recombination rate modulates the distribution of putatively deleterious variants across the entire human genome. Exons in regions of low recombination are significantly enriched for deleterious and disease-associated variants, a signature varying in strength across worldwide human populations with different demographic histories. Regions with low recombination rates are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effects on health, a phenomenon likely affecting disease susceptibility in humans.
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U2 - 10.1038/ng.3216
DO - 10.1038/ng.3216
M3 - Article
C2 - 25685891
AN - SCOPUS:84925871417
SN - 1061-4036
VL - 47
SP - 400
EP - 404
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -