Monday, September 30, 2013

Fwd: Whole-Exome Sequencing Reveals a Rapid Change in the Frequency of Rare Functional Variants in a Founding Population of Humans

Our rare variants in the light of artefacts. Occam's razor of discovery.
Fwd: please follow footer link

Whole-Exome Sequencing Reveals a Rapid Change in the Frequency of Rare Functional Variants in a Founding Population of Humans: "

by Ferran Casals, Alan Hodgkinson, Julie Hussin, Youssef Idaghdour, Vanessa Bruat, Thibault de Maillard, Jean-Cristophe Grenier, Elias Gbeha, Fadi F. Hamdan, Simon Girard, Jean-François Spinella, Mathieu Larivière, Virginie Saillour, Jasmine Healy, Isabel Fernández, Daniel Sinnett, Jacques L. Michaud, Guy A. Rouleau, Elie Haddad, Françoise Le Deist, Philip Awadalla


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."

(Via PLOS Genetics.)