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

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

Research output: Contribution to journalArticlepeer-review


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
Issue number4
StatePublished - Apr 28 2015

ASJC Scopus subject areas

  • Genetics


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