fr
Article scientifique
Accès libre
Anglais

An integrated map of genetic variation from 1,092 human genomes

Contributeurs/trices1000 Genomes Project Consortium
Collaborateurs/tricesDermitzakis, Emmanouil
Publié dansNature, vol. 491, no. 7422, p. 56-65
Date de publication2012
Résumé

By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.

Mots-clés
  • Alleles
  • Binding Sites/genetics
  • Conserved Sequence/genetics
  • Continental Population Groups/genetics
  • Evolution, Molecular
  • Genetic Variation/genetics
  • Genetics, Medical
  • Genetics, Population
  • Genome, Human/genetics
  • Genome-Wide Association Study
  • Genomics
  • Haplotypes/genetics
  • Humans
  • Nucleotide Motifs
  • Polymorphism, Single Nucleotide/genetics
  • Sequence Deletion/genetics
  • Transcription Factors/metabolism
Citation (format ISO)
1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. In: Nature, 2012, vol. 491, n° 7422, p. 56–65. doi: 10.1038/nature11632
Fichiers principaux (1)
Article (Published version)
accessLevelPublic
Identifiants
ISSN du journal0028-0836
896vues
665téléchargements

Informations techniques

Création13/01/2015 13:43:00
Première validation13/01/2015 13:43:00
Heure de mise à jour14/03/2023 22:41:04
Changement de statut14/03/2023 22:41:04
Dernière indexation16/01/2024 15:52:14
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack