Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS Genet. 2013;9(9):e1003815. doi: 10.1371/journal.pgen.1003815. Epub 2013 Sep 26.

Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans.

Author information

1
Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.

Erratum in

  • PLoS Genet. 2014 Feb;10(2):e1004260. Grenier, Jean-Cristophe [corrected to Grenier, Jean-Christophe].

Abstract

Whole-exome or gene targeted resequencing in hundreds to thousands of individuals has shown that the majority of genetic variants are at low frequency in human populations. Rare variants are enriched for functional mutations and are expected to explain an important fraction of the genetic etiology of human disease, therefore having a potential medical interest. In this work, we analyze the whole-exome sequences of French-Canadian individuals, a founder population with a unique demographic history that includes an original population bottleneck less than 20 generations ago, followed by a demographic explosion, and the whole exomes of French individuals sampled from France. We show that in less than 20 generations of genetic isolation from the French population, the genetic pool of French-Canadians shows reduced levels of diversity, higher homozygosity, and an excess of rare variants with low variant sharing with Europeans. Furthermore, the French-Canadian population contains a larger proportion of putatively damaging functional variants, which could partially explain the increased incidence of genetic disease in the province. Our results highlight the impact of population demography on genetic fitness and the contribution of rare variants to the human genetic variation landscape, emphasizing the need for deep cataloguing of genetic variants by resequencing worldwide human populations in order to truly assess disease risk.

PMID:
24086152
PMCID:
PMC3784517
DOI:
10.1371/journal.pgen.1003815
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center