The landscape of tolerated genetic variation in humans and primates

Resource type
Journal article
Creator (person)
Gao, Hong
Hamp, Tobias
Ede, Jeffrey
Schraiber, Joshua G
McRae, Jeremy
Singer-Berk, Moriel
Yang, Yanshen
Dietrich, Anastasia S D
Fiziev, Petko P
Kuderna, Lukas F K
Sundaram, Laksshman
Wu, Yibing
Adhikari, Aashish
Field, Yair
Chen, Chen
Batzoglou, Serafim
Aguet, Francois
Lemire, Gabrielle
Reimers, Rebecca
Balick, Daniel
Janiak, Mareike C
Kuhlwilm, Martin
Orkin, Joseph D
Manu, Shivakumara
Valenzuela, Alejandro
Bergman, Juraj
Rousselle, Marjolaine
Silva, Felipe Ennes
Agueda, Lidia
Blanc, Julie
Gut, Marta
de Vries, Dorien
Goodhead, Ian
Harris, R. Alan
Raveendran, Muthuswamy
Jensen, Axel
Chuma, Idriss S
Horvath, Julie E
Hvilsom, Christina
Juan, David
Frandsen, Peter
de Melo, Fabiano R
Bertuol, Fabrà­cio
Byrne, Hazel
Sampaio, Iracilda
Farias, Izeni
do Amaral, Joà£o Valsecchi
Messias, Mariluce
da Silva, Maria N F
Trivedi, Mihir
Rossi, Rogerio
Hrbek, Tomas
Andriaholinirina, Nicole
Rabarivola, Clément J
Zaramody, Alphonse
Jolly, Clifford J
Phillips-Conroy, Jane
Wilkerson, Gregory
Abee, Christian
Simmons, Joe H
Fernandez-Duque, Eduardo
Kanthaswamy, Sree
Shiferaw, Fekadu
Wu, Dongdong
Zhou, Long
Shao, Yong
Zhang, Guojie
Keyyu, Julius D
Knauf, Sascha
Le, Minh D
Lizano, Esther
Merker, Stefan
Navarro, Arcadi
Bataillon, Thomas
Nadler, Tilo
Khor, Chiea Chuen
Lee, Jessica
Tan, Patrick
Lim, Weng Khong
Kitchener, Andrew C
Zinner, Dietmar
Gut, Ivo
Melin, Amanda
Guschanski, Katerina
Schierup, Mikkel Heide
Beck, Robin M D
Umapathy, Govindhaswamy
Roos, Christian
Boubli, Jean P
Lek, Monkol
Sunyaev, Shamil
O’Donnell-Luria, Anne
Rehm, Heidi L
Xu, Jinbo
Rogers, Jeffrey
Marques-Bonet, Tomas
Farh, Kyle Kai-How
Date published
June 2, 2023
Abstract
Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
Journal title
Science
Volume
380
Issue
6648
Publisher
American Association for the Advancement of Science (AAAS)
ISSN
0036-8075
eISSN
1095-9203
Date accepted
December 31, 2021
Official URL
Related URL
Rights statement
In Copyright
DOI
Keywords