Article
The mutational constraint spectrum quantified from variation in 141,456 humans.
Nature - 1 May 2020
Karczewski Konrad J, Francioli Laurent C, Tiao Grace, Cummings Beryl B, Alföldi Jessica, Wang Qingbo, Collins Ryan L, Laricchia Kristen M, Ganna Andrea, Birnbaum Daniel P, Gauthier Laura D, Brand Harrison, Solomonson Matthew, Watts Nicholas A, Rhodes Daniel, Singer-Berk Moriel, England Eleina M, Seaby Eleanor G, Kosmicki Jack A, Walters Raymond K, Tashman Katherine, Farjoun Yossi, Banks Eric, Poterba Timothy, Wang Arcturus, Seed Cotton, Whiffin Nicola, Chong Jessica X, Samocha Kaitlin E, Pierce-Hoffman Emma, Zappala Zachary, O'Donnell-Luria Anne H, Minikel Eric Vallabh, Weisburd Ben, Lek Monkol, Ware James S, Vittal Christopher, Armean Irina M, Bergelson Louis, Cibulskis Kristian, Connolly Kristen M, Covarrubias Miguel, Donnelly Stacey, Ferriera Steven, Gabriel Stacey, Gentry Jeff, Gupta Namrata, Jeandet Thibault, Kaplan Diane, Llanwarne Christopher, Munshi Ruchi, Novod Sam, Petrillo Nikelle, Roazen David, Ruano-Rubio Valentin, Saltzman Andrea, Schleicher Molly, Soto Jose, Tibbetts Kathleen, Tolonen Charlotte, Wade Gordon, Talkowski Michael E, Neale Benjamin M, Daly Mark J, MacArthur Daniel G
Abstract excerpt
Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be...
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