The landscape of tolerated genetic variation in humans and primates.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
02 06 2023
02 06 2023
Historique:
medline:
5
6
2023
pubmed:
1
6
2023
entrez:
1
6
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37262156
doi: 10.1126/science.abn8197
pmc: PMC10713091
mid: NIHMS1919567
doi:
Types de publication
Dataset
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabn8153Subventions
Organisme : NIA NIH HHS
ID : P30 AG012836
Pays : United States
Organisme : NICHD NIH HHS
ID : R24 HD044964
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM089753
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007748
Pays : United States
Organisme : NIH HHS
ID : P40 OD024628
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : CommentIn
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