Recombination affects accumulation of damaging and disease-associated mutations in human populations

Julie G. Hussin, Alan Hodgkinson, Youssef Idaghdhour, Jean Christophe Grenier, Jean Philippe Goulet, Elias Gbeha, Elodie Hip-Ki, Philip Awadalla

    Research output: Contribution to journalArticle

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)400-404
    Number of pages5
    JournalNature Genetics
    Volume47
    Issue number4
    DOIs
    StatePublished - Jan 1 2015

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    Genetic Recombination
    Mutation
    Chromosomes
    Population
    Essential Genes
    Disease Susceptibility
    Human Genome
    Exons
    Demography
    Genome
    Health

    ASJC Scopus subject areas

    • Genetics

    Cite this

    Hussin, J. G., Hodgkinson, A., Idaghdhour, Y., Grenier, J. C., Goulet, J. P., Gbeha, E., ... Awadalla, P. (2015). Recombination affects accumulation of damaging and disease-associated mutations in human populations. Nature Genetics, 47(4), 400-404. https://doi.org/10.1038/ng.3216

    Recombination affects accumulation of damaging and disease-associated mutations in human populations. / Hussin, Julie G.; Hodgkinson, Alan; Idaghdhour, Youssef; Grenier, Jean Christophe; Goulet, Jean Philippe; Gbeha, Elias; Hip-Ki, Elodie; Awadalla, Philip.

    In: Nature Genetics, Vol. 47, No. 4, 01.01.2015, p. 400-404.

    Research output: Contribution to journalArticle

    Hussin, JG, Hodgkinson, A, Idaghdhour, Y, Grenier, JC, Goulet, JP, Gbeha, E, Hip-Ki, E & Awadalla, P 2015, 'Recombination affects accumulation of damaging and disease-associated mutations in human populations', Nature Genetics, vol. 47, no. 4, pp. 400-404. https://doi.org/10.1038/ng.3216
    Hussin JG, Hodgkinson A, Idaghdhour Y, Grenier JC, Goulet JP, Gbeha E et al. Recombination affects accumulation of damaging and disease-associated mutations in human populations. Nature Genetics. 2015 Jan 1;47(4):400-404. https://doi.org/10.1038/ng.3216
    Hussin, Julie G. ; Hodgkinson, Alan ; Idaghdhour, Youssef ; Grenier, Jean Christophe ; Goulet, Jean Philippe ; Gbeha, Elias ; Hip-Ki, Elodie ; Awadalla, Philip. / Recombination affects accumulation of damaging and disease-associated mutations in human populations. In: Nature Genetics. 2015 ; Vol. 47, No. 4. pp. 400-404.
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