The landscape of tolerated genetic variation in humans and primates.
bioRxiv
; 2023 May 02.
Article
em En
| MEDLINE
| ID: mdl-37205491
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 human. We show that these variants can be inferred to have non-deleterious effects in human 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. One Sentence Summary:
Deep learning classifier trained on 4.3 million common primate missense variants predicts variant pathogenicity in humans.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos