| 论文题目: | The Landscape of Tolerated Genetic Variation in Humans and Primates |
| 作者: | 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; etc |
| 联系作者: | tomas.marques@upf.edu |
| 发表年度: | 2023 |
| DOI: | doi: 10.1126/science.abn8197 |
| 摘要: | 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 disease |
| 刊物名称: | Science |
| 论文出处: | https://www.science.org/doi/10.1126/science.abn8197 |
| 影响因子: | 56.9(2022IF) |
