RT Journal Article
SR Electronic
T1 Analysis of protein-coding genetic variation in 60,706 humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 030338
DO 10.1101/030338
A1 ,
A1 Lek, Monkol
A1 Karczewski, Konrad J
A1 Minikel, Eric V
A1 Samocha, Kaitlin E
A1 Banks, Eric
A1 Fennell, Timothy
A1 O’Donnell-Luria, Anne H
A1 Ware, James S
A1 Hill, Andrew J
A1 Cummings, Beryl B
A1 Tukiainen, Taru
A1 Birnbaum, Daniel P
A1 Kosmicki, Jack A
A1 Duncan, Laramie
A1 Estrada, Karol
A1 Zhao, Fengmei
A1 Zou, James
A1 Pierce-Hoffman, Emma
A1 Cooper, David N
A1 DePristo, Mark
A1 Do, Ron
A1 Flannick, Jason
A1 Fromer, Menachem
A1 Gauthier, Laura
A1 Goldstein, Jackie
A1 Gupta, Namrata
A1 Howrigan, Daniel
A1 Kiezun, Adam
A1 Kurki, Mitja I
A1 Moonshine, Ami Levy
A1 Natarajan, Pradeep
A1 Orozco, Lorena
A1 Peloso, Gina M
A1 Poplin, Ryan
A1 Rivas, Manuel A
A1 Ruano-Rubio, Valentin
A1 Ruderfer, Douglas M
A1 Shakir, Khalid
A1 Stenson, Peter D
A1 Stevens, Christine
A1 Thomas, Brett P
A1 Tiao, Grace
A1 Tusie-Luna, Maria T
A1 Weisburd, Ben
A1 Won, Hong-Hee
A1 Yu, Dongmei
A1 Altshuler, David M
A1 Ardissino, Diego
A1 Boehnke, Michael
A1 Danesh, John
A1 Elosua, Roberto
A1 Florez, Jose C
A1 Gabriel, Stacey B
A1 Getz, Gad
A1 Hultman, Christina M
A1 Kathiresan, Sekar
A1 Laakso, Markku
A1 McCarroll, Steven
A1 McCarthy, Mark I
A1 McGovern, Dermot
A1 McPherson, Ruth
A1 Neale, Benjamin M
A1 Palotie, Aarno
A1 Purcell, Shaun M
A1 Saleheen, Danish
A1 Scharf, Jeremiah
A1 Sklar, Pamela
A1 Sullivan, Patrick F
A1 Tuomilehto, Jaakko
A1 Watkins, Hugh C
A1 Wilson, James G
A1 Daly, Mark J
A1 MacArthur, Daniel G
YR 2015
UL http://biorxiv.org/content/early/2015/10/30/030338.abstract
AB Large-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) sequence data for 60,706 individuals of diverse ethnicities. The resulting catalogue of human genetic diversity has unprecedented resolution, with an average of one variant every eight bases of coding sequence and the presence of widespread mutational recurrence. The deep catalogue of variation provided by the Exome Aggregation Consortium (ExAC) can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 79% of which have no currently established human disease phenotype. Finally, we show 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.