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 Exome Aggregation Consortium
A1 Monkol Lek
A1 Konrad J Karczewski
A1 Eric V Minikel
A1 Kaitlin E Samocha
A1 Eric Banks
A1 Timothy Fennell
A1 Anne H O’Donnell-Luria
A1 James S Ware
A1 Andrew J Hill
A1 Beryl B Cummings
A1 Taru Tukiainen
A1 Daniel P Birnbaum
A1 Jack A Kosmicki
A1 Laramie Duncan
A1 Karol Estrada
A1 Fengmei Zhao
A1 James Zou
A1 Emma Pierce-Hoffman
A1 David N Cooper
A1 Mark DePristo
A1 Ron Do
A1 Jason Flannick
A1 Menachem Fromer
A1 Laura Gauthier
A1 Jackie Goldstein
A1 Namrata Gupta
A1 Daniel Howrigan
A1 Adam Kiezun
A1 Mitja I Kurki
A1 Ami Levy Moonshine
A1 Pradeep Natarajan
A1 Lorena Orozco
A1 Gina M Peloso
A1 Ryan Poplin
A1 Manuel A Rivas
A1 Valentin Ruano-Rubio
A1 Douglas M Ruderfer
A1 Khalid Shakir
A1 Peter D Stenson
A1 Christine Stevens
A1 Brett P Thomas
A1 Grace Tiao
A1 Maria T Tusie-Luna
A1 Ben Weisburd
A1 Hong-Hee Won
A1 Dongmei Yu
A1 David M Altshuler
A1 Diego Ardissino
A1 Michael Boehnke
A1 John Danesh
A1 Roberto Elosua
A1 Jose C Florez
A1 Stacey B Gabriel
A1 Gad Getz
A1 Christina M Hultman
A1 Sekar Kathiresan
A1 Markku Laakso
A1 Steven McCarroll
A1 Mark I McCarthy
A1 Dermot McGovern
A1 Ruth McPherson
A1 Benjamin M Neale
A1 Aarno Palotie
A1 Shaun M Purcell
A1 Danish Saleheen
A1 Jeremiah Scharf
A1 Pamela Sklar
A1 Patrick F Sullivan
A1 Jaakko Tuomilehto
A1 Hugh C Watkins
A1 James G Wilson
A1 Mark J Daly
A1 Daniel G MacArthur
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.