A map of human genome variation from population-scale sequencing
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Résumé
The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother–father–child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. This issue of Nature contains the first publication from The 1000 Genomes Project, an international collaboration that will produce an extensive public catalogue of human genetic variation. The plan, in fact, is to sequence about 2,000 unidentified individuals from 20 populations around the world. This first paper presents the results from the project's pilot phase, testing three different strategies for genome-wide sequencing with high-throughput platforms: low-coverage whole-genome sequencing of 179 individuals in three population groups, high-coverage sequencing of two mother–father–child trios, and exon-targeted sequencing of 697 individuals from seven populations. The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.
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La notice
- Revue
- Nature
- Thématique
- Genomics and Rare Diseases
- Domaine
- Biochemistry, Genetics and Molecular Biology
- Établissements canadiens
- Simon Fraser UniversityUniversité de MontréalCentre Hospitalier de l’Université de MontréalMcGill University
- Organismes subventionnaires
- National Center for Research ResourcesNational Institute of Environmental Health SciencesNational Institute of General Medical SciencesNational Human Genome Research InstituteNational Institute of Mental HealthNational High-tech Research and Development ProgramEngineering and Physical Sciences Research CouncilMax-Planck-GesellschaftHoward Hughes Medical InstituteNational Natural Science Foundation of ChinaLouis-Jeantet FoundationDeutsche ForschungsgemeinschaftLeverhulme TrustGovernment of Jiangxi ProvinceBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchNational Institute on Alcohol Abuse and AlcoholismNational Key Research and Development Program of ChinaU.S. National Library of MedicineBritish Heart FoundationDoris Duke Charitable FoundationWellcome TrustTranslational Genomics Research InstituteNational Science FoundationPew Charitable TrustsNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungMedical Research CouncilMinistero dello Sviluppo Economico
- Mots-clés
- 1000 Genomes ProjectGeneticsBiologyGenomeHuman genomeStructural variationHaplotypeReference genomeDNA sequencingGenomicsPopulationAllele frequencyComputational biologySingle-nucleotide polymorphismAlleleGeneGenotype
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