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

Casals Ferran, Hodgkinson Alan, Hussin Julie, Idaghdour Youssef, Bruat Vanessa, de Maillard Thibault, Grenier Jean-Christophe, Gbeha Elias, Hamdan Fadi F., Girard Simon, Spinella Jean-François, Larivière Mathieu, Saillour Virginie, Healy Jasmine, Fernández Isabel, Sinnett Daniel, Michaud Jacques L., Rouleau Guy A., Haddad Elie, Le Deist Françoise et Awadalla Philip. (2013). Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans. PloS Genetics, 9, (9), e100381.

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URL officielle: https://dx.doi.org/doi:10.1371/journal.pgen.100381...

Résumé

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.

Type de document:Article publié dans une revue avec comité d'évaluation
Volume:9
Numéro:9
Pages:e100381
Version évaluée par les pairs:Oui
Date:2013
Sujets:Sciences de la santé > Sciences médicales > Génétique
Département, module, service et unité de recherche:Départements et modules > Département des sciences fondamentales
Mots-clés:population genetics, human genomes, polymorphism, mutation, founder population, exome sequencing, disease
Déposé le:28 août 2019 01:04
Dernière modification:28 août 2019 01:04
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