RT Journal Article
SR Electronic
T1 Recombination impacts damaging and disease mutations accumulation in human populations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 006064
DO 10.1101/006064
A1 Julie G. Hussin
A1 Alan Hodgkinson
A1 Youssef Idaghdour
A1 Jean-Christophe Grenier
A1 Jean-Philippe Goulet
A1 Elias Gbeha
A1 Elodie Hip-Ki
A1 Philip Awadalla
YR 2014
UL http://biorxiv.org/content/early/2014/06/08/006064.abstract
AB Many decades of theory have demonstrated that in non-recombining systems, slightly deleterious mutations accumulate non-reversibly1, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion2, however it is not clear the extent to which these processes operate along recombining chromosomes with highly variable rates of crossing over. Using high coverage sequencing data from over 1400 individuals, we show that recombination rate modulates the genomic distribution of putatively deleterious variants across the entire human genome. We find that exons in regions of low recombination are significantly enriched for deleterious and disease variants, a signature that varies in strength across worldwide human populations with different demographic histories. As low recombining regions are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effect on health, this phenomenon likely affects disease susceptibility in humans.