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dc.contributor.authorAltshuler, David Matthew
dc.contributor.authorLander, Eric Steven
dc.contributor.authorAmbrogio, Lauren
dc.contributor.authorBloom, Toby
dc.contributor.authorCibulskis, Kristian
dc.contributor.authorFennell, Tim J.
dc.contributor.authorGabriel, Stacey B.
dc.contributor.authorJaffe, David B.
dc.contributor.authorShefler, Erica
dc.contributor.authorSougnez, Carrie L.
dc.contributor.authorLee, Charles
dc.contributor.authorMills, Ryan Edward
dc.contributor.authorShi, Xinghua
dc.contributor.authorDaly, Mark Joseph
dc.contributor.authorDePristo, Mark A.
dc.contributor.authorBall, Aaron D.
dc.contributor.authorBanks, Eric
dc.contributor.authorBrowning, Brian L.
dc.contributor.authorGarimella, Kiran V.
dc.contributor.authorGrossman, Sharon Rachel
dc.contributor.authorHandsaker, Robert E
dc.contributor.authorHanna, Matt
dc.contributor.authorHartl, Chris
dc.contributor.authorKernytsky, Andrew M.
dc.contributor.authorKorn, Joshua M.
dc.contributor.authorLi, Heng
dc.contributor.authorMaguire, Jared R.
dc.contributor.authorMcCarroll, Steven A.
dc.contributor.authorNemesh, James C.
dc.contributor.authorMcKenna, Aaron
dc.contributor.authorPhilippakis, Anthony Andrew
dc.contributor.authorPoplin, Ryan E.
dc.contributor.authorPrice, Alkes
dc.contributor.authorRivas, Manuel A.
dc.contributor.authorSabeti, Pardis Christine
dc.contributor.authorSchaffner, Stephen
dc.contributor.authorShlyakhter, Ilya
dc.date.accessioned2011-11-02T19:20:29Z
dc.date.issued2010
dc.identifier.citationDurbin, Richard M., David Altshuler, Gonçalo R. Abecasis, David R. Bentley, Aravinda Chakravarti, Andrew G. Clark, Francis S. Collins et al. 2010. A map of human genome variation from population-scale sequencing. Nature 467(7319): 1061-1073.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.issn1476-4687en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5339502
dc.description.abstractThe 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.en_US
dc.description.sponsorshipOrganismic and Evolutionary Biologyen_US
dc.description.sponsorshipOther Research Uniten_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/nature09534en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/20981092en_US
dash.licenseOAP
dc.subjectwide associationen_US
dc.subjectgene-expressionen_US
dc.subjectgene-expressionen_US
dc.subjectrecombination hotspotsen_US
dc.subjectmeiotic recombinationen_US
dc.subjectgenotype imputationen_US
dc.subjectrare variantsen_US
dc.subjecthaplotype mapen_US
dc.subjectnucleotideen_US
dc.subjectdiseasesen_US
dc.titleA Map of Human Genome Variation from Population Scale Sequencingen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNatureen_US
dash.depositing.authorSabeti, Pardis Christine
dc.date.available2011-11-02T19:20:29Z
dash.affiliation.otherThe Broad Institute of MIT and Harvarden_US
dash.affiliation.otherHarvard Medical School, Department of Geneticsen_US
dash.affiliation.otherHarvard Medical School, Department of Pathologyen_US
dash.affiliation.otherHarvard School of Public Health, Department of Epidemiologyen_US
dash.affiliation.otherHarvard School of Public Health, Departments of Epidemiology and Biostatisticsen_US
dc.identifier.doi10.1038/nature09534*
dash.authorsorderedfalse
dash.contributor.affiliatedPhilippakis, Anthony Andrew
dash.contributor.affiliatedMills, Ryan Edward
dash.contributor.affiliatedShi, Xinghua
dash.contributor.affiliatedGrossman, Sharon
dash.contributor.affiliatedShlyakhter, Ilya
dash.contributor.affiliatedSchaffner, Stephen
dash.contributor.affiliatedLee, Charles
dash.contributor.affiliatedHandsaker, Robert
dash.contributor.affiliatedMcCarroll, Steven
dash.contributor.affiliatedPrice, Alkes
dash.contributor.affiliatedLi, Heng
dash.contributor.affiliatedSabeti, Pardis
dash.contributor.affiliatedLander, Eric
dash.contributor.affiliatedDaly, Mark
dash.contributor.affiliatedAltshuler, David


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