title: Recombination affects accumulation of damaging and disease-associated mutations in human populations.
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.
authors: 1] Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. [2] CARTaGENE Project, Sainte-Justine University Hospital, Montreal, Quebec, Canada.
authors: Julie G
authors: JG
authors: Hussin
authors: 1] Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. [2] CARTaGENE Project, Sainte-Justine University Hospital, Montreal, Quebec, Canada.
authors: Alan
authors: A
authors: Hodgkinson
authors: 1] Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. [2] CARTaGENE Project, Sainte-Justine University Hospital, Montreal, Quebec, Canada.
authors: Youssef
authors: Y
authors: Idaghdour
authors: Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors: Jean-Christophe
authors: JC
authors: Grenier
authors: CARTaGENE Project, Sainte-Justine University Hospital, Montreal, Quebec, Canada.
authors: Jean-Philippe
authors: JP
authors: Goulet
authors: Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors: Elias
authors: E
authors: Gbeha
authors: Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors: Elodie
authors: E
authors: Hip-Ki
authors: 1] Sainte-Justine University Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. [2] CARTaGENE Project, Sainte-Justine University Hospital, Montreal, Quebec, Canada.
authors: Philip
authors: P
authors: Awadalla
mesh_terms: D000818:Animals; D003434:Crossing Over, Genetic; D004249:DNA Damage / Q000235:genetics; D004194:Disease / Q000235:genetics*; D019143:Evolution, Molecular; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D059645:Mutation Rate; D002679:Pan troglodytes; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*; D011995:Recombination, Genetic / Q000502:physiology*