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dc.contributor.authorLek, Monkol
dc.contributor.authorKarczewski, Konrad J
dc.contributor.authorMinikel, Eric V
dc.contributor.authorSamocha, Kaitlin E
dc.contributor.authorBanks, Eric
dc.contributor.authorFennell, Timothy
dc.contributor.authorO'Donnell-Luria, Anne H
dc.contributor.authorWare, James S
dc.contributor.authorHill, Andrew J
dc.contributor.authorCummings, Beryl B
dc.contributor.authorTukiainen, Taru
dc.contributor.authorBirnbaum, Daniel P
dc.contributor.authorKosmicki, Jack A
dc.contributor.authorDuncan, Laramie E
dc.contributor.authorEstrada, Karol
dc.contributor.authorZhao, Fengmei
dc.contributor.authorZou, James
dc.contributor.authorPierce-Hoffman, Emma
dc.contributor.authorBerghout, Joanne
dc.contributor.authorCooper, David N
dc.contributor.authorDeflaux, Nicole
dc.contributor.authorDePristo, Mark
dc.contributor.authorDo, Ron
dc.contributor.authorFlannick, Jason
dc.contributor.authorFromer, Menachem
dc.contributor.authorGauthier, Laura
dc.contributor.authorGoldstein, Jackie
dc.contributor.authorGupta, Namrata
dc.contributor.authorHowrigan, Daniel
dc.contributor.authorKiezun, Adam
dc.contributor.authorKurki, Mitja I
dc.contributor.authorMoonshine, Ami Levy
dc.contributor.authorNatarajan, Pradeep
dc.contributor.authorOrozco, Lorena
dc.contributor.authorPeloso, Gina M
dc.contributor.authorPoplin, Ryan
dc.contributor.authorRivas, Manuel A
dc.contributor.authorRuano-Rubio, Valentin
dc.contributor.authorRose, Samuel A
dc.contributor.authorRuderfer, Douglas M
dc.contributor.authorShakir, Khalid
dc.contributor.authorStenson, Peter D
dc.contributor.authorStevens, Christine
dc.contributor.authorThomas, Brett P
dc.contributor.authorTiao, Grace
dc.contributor.authorTusie-Luna, Maria T
dc.contributor.authorWeisburd, Ben
dc.contributor.authorWon, Hong-Hee
dc.contributor.authorYu, Dongmei
dc.contributor.authorAltshuler, David M
dc.contributor.authorArdissino, Diego
dc.contributor.authorBoehnke, Michael
dc.contributor.authorDanesh, John
dc.contributor.authorDonnelly, Stacey
dc.contributor.authorElosua, Roberto
dc.contributor.authorFlorez, Jose C
dc.contributor.authorGabriel, Stacey B
dc.contributor.authorGetz, Gad
dc.contributor.authorGlatt, Stephen J
dc.contributor.authorHultman, Christina M
dc.contributor.authorKathiresan, Sekar
dc.contributor.authorLaakso, Markku
dc.contributor.authorMcCarroll, Steven
dc.contributor.authorMcCarthy, Mark I
dc.contributor.authorMcGovern, Dermot
dc.contributor.authorMcPherson, Ruth
dc.contributor.authorNeale, Benjamin M
dc.contributor.authorPalotie, Aarno
dc.contributor.authorPurcell, Shaun M
dc.contributor.authorSaleheen, Danish
dc.contributor.authorScharf, Jeremiah M
dc.contributor.authorSklar, Pamela
dc.contributor.authorSullivan, Patrick F
dc.contributor.authorTuomilehto, Jaakko
dc.contributor.authorTsuang, Ming T
dc.contributor.authorWatkins, Hugh C
dc.contributor.authorWilson, James G
dc.contributor.authorDaly, Mark J
dc.contributor.authorMacArthur, Daniel G
dc.contributor.authorExome Aggregation Consortium
dc.date.accessioned2018-01-11T15:17:55Z
dc.date.available2018-01-11T15:17:55Z
dc.date.issued2016-08-18
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/270516
dc.description.abstractLarge-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.
dc.format.mediumPrint
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectExome Aggregation Consortium
dc.subjectHumans
dc.subjectRare Diseases
dc.subjectProteome
dc.subjectSample Size
dc.subjectDNA Mutational Analysis
dc.subjectPhenotype
dc.subjectGenetic Variation
dc.subjectExome
dc.subjectDatasets as Topic
dc.titleAnalysis of protein-coding genetic variation in 60,706 humans.
dc.typeArticle
prism.endingPage291
prism.issueIdentifier7616
prism.publicationDate2016
prism.publicationNameNature
prism.startingPage285
prism.volume536
dc.identifier.doi10.17863/CAM.17413
dcterms.dateAccepted2016-06-24
rioxxterms.versionofrecord10.1038/nature19057
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-08
dc.contributor.orcidDanesh, John [0000-0003-1158-6791]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/P02811X/1)
pubs.funder-project-idEuropean Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
pubs.funder-project-idBritish Heart Foundation (CH/12/2/29428)
pubs.funder-project-idMedical Research Council (MR/P013880/1)
pubs.funder-project-idUme� University (unknown)
pubs.funder-project-idNHS Blood and Transplant (NHSBT) (WP12-01)
pubs.funder-project-idEuropean Commission (279143)
pubs.funder-project-idNHS Blood and Transplant (NHSBT) (11-01-GEN)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idEuropean Commission (279233)
pubs.funder-project-idEuropean Research Council (268834)
pubs.funder-project-idMRC (MR/J015709/1)
pubs.funder-project-idMRC (MR/J006602/1)
pubs.funder-project-idMRC (MR/J006599/1)
pubs.funder-project-idMedical Research Council (MR/M012816/1)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idBritish Heart Foundation (RG/16/4/32218)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-25)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NIHR BTRU-2014-10024)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1516-29)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
cam.issuedOnline2016-08-17


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International