文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

Analysis of protein-coding genetic variation in 60,706 humans.

作者信息

Lek Monkol, Karczewski Konrad J, Minikel Eric V, Samocha Kaitlin E, Banks Eric, Fennell Timothy, O'Donnell-Luria Anne H, Ware James S, Hill Andrew J, Cummings Beryl B, Tukiainen Taru, Birnbaum Daniel P, Kosmicki Jack A, Duncan Laramie E, Estrada Karol, Zhao Fengmei, Zou James, Pierce-Hoffman Emma, Berghout Joanne, Cooper David N, Deflaux Nicole, DePristo Mark, Do Ron, Flannick Jason, Fromer Menachem, Gauthier Laura, Goldstein Jackie, Gupta Namrata, Howrigan Daniel, Kiezun Adam, Kurki Mitja I, Moonshine Ami Levy, Natarajan Pradeep, Orozco Lorena, Peloso Gina M, Poplin Ryan, Rivas Manuel A, Ruano-Rubio Valentin, Rose Samuel A, Ruderfer Douglas M, Shakir Khalid, Stenson Peter D, Stevens Christine, Thomas Brett P, Tiao Grace, Tusie-Luna Maria T, Weisburd Ben, Won Hong-Hee, Yu Dongmei, Altshuler David M, Ardissino Diego, Boehnke Michael, Danesh John, Donnelly Stacey, Elosua Roberto, Florez Jose C, Gabriel Stacey B, Getz Gad, Glatt Stephen J, Hultman Christina M, Kathiresan Sekar, Laakso Markku, McCarroll Steven, McCarthy Mark I, McGovern Dermot, McPherson Ruth, Neale Benjamin M, Palotie Aarno, Purcell Shaun M, Saleheen Danish, Scharf Jeremiah M, Sklar Pamela, Sullivan Patrick F, Tuomilehto Jaakko, Tsuang Ming T, Watkins Hugh C, Wilson James G, Daly Mark J, MacArthur Daniel G

机构信息

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

出版信息

Nature. 2016 Aug 18;536(7616):285-91. doi: 10.1038/nature19057.

DOI:10.1038/nature19057
PMID:27535533
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5018207/
Abstract

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/5fa49e414c60/nihms798561f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/9e99e01ee73c/nihms798561f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/f814f14e9a6d/nihms798561f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/adc0cefd6f2d/nihms798561f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/46e7d67f6eb2/nihms798561f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/c140f17e85e0/nihms798561f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/99bf5af20bf6/nihms798561f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/683e07086777/nihms798561f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/f79ea9a2ad83/nihms798561f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/9d8741fbf9c6/nihms798561f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/5fa49e414c60/nihms798561f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/9e99e01ee73c/nihms798561f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/f814f14e9a6d/nihms798561f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/adc0cefd6f2d/nihms798561f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/46e7d67f6eb2/nihms798561f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/c140f17e85e0/nihms798561f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/99bf5af20bf6/nihms798561f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/683e07086777/nihms798561f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/f79ea9a2ad83/nihms798561f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/9d8741fbf9c6/nihms798561f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d518/5018207/5fa49e414c60/nihms798561f5.jpg

相似文献

[1]
Analysis of protein-coding genetic variation in 60,706 humans.

Nature. 2016-8-18

[2]
Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Genome Med. 2017-2-6

[3]
Diagnosing rare diseases after the exome.

Cold Spring Harb Mol Case Stud. 2018-12-17

[4]
A deep catalogue of protein-coding variation in 983,578 individuals.

Nature. 2024-7

[5]
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Am J Hum Genet. 2017-1-5

[6]
Using high-resolution variant frequencies to empower clinical genome interpretation.

Genet Med. 2017-5-18

[7]
ExAC project pins down rare gene variants.

Nature. 2016-8-18

[8]
Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke: The NHLBI Exome Sequence Project.

JAMA Neurol. 2015-7

[9]
Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes.

Gut. 2012-4-28

[10]
A global reference for human genetic variation.

Nature. 2015-10-1

引用本文的文献

[1]
Associations of Rare Variants in the Gene with Bipolar Disorder in Chinese Population.

Neuropsychiatr Dis Treat. 2025-8-29

[2]
Variant classification of hereditary cancer genes is affected by genomic underrepresentation of admixed populations.

Mol Genet Genomics. 2025-9-3

[3]
Persistent Tic Disorders Are Associated With 17q12 Duplications.

Res Sq. 2025-8-19

[4]
Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty.

Res Sq. 2025-8-21

[5]
Identification of the potential pathogenicity of a VUS in the ASL gene associated with argininosuccinic aciduria in an Iranian family.

Mol Biol Rep. 2025-8-29

[6]
Established Cancer Predisposition Genes in Single and Multiple Cancer Diagnoses.

JAMA Oncol. 2025-8-28

[7]
A Case of Infantile Epileptic Spasms Syndrome with the Mutation and Review of βII-Spectrin Variants.

Genes (Basel). 2025-7-29

[8]
Heterozygous variants in affect hearing, vision, cardiac, and immune function.

Elife. 2025-8-27

[9]
Increasing pathogenic germline variant diagnosis rates in precision medicine: current best practices and future opportunities.

Hum Genomics. 2025-8-22

[10]
Epilepsy in NHS actin remodeling regulator gene (NHS) and genotype-phenotype correlations.

Pediatr Res. 2025-8-15

本文引用的文献

[1]
Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.

Nature. 2017-4-12

[2]
Health and population effects of rare gene knockouts in adult humans with related parents.

Science. 2016-4-22

[3]
Quantifying prion disease penetrance using large population control cohorts.

Sci Transl Med. 2016-1-20

[4]
The human gene damage index as a gene-level approach to prioritizing exome variants.

Proc Natl Acad Sci U S A. 2015-11-3

[5]
Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data.

PLoS Genet. 2015-10-8

[6]
A global reference for human genetic variation.

Nature. 2015-10-1

[7]
The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.

Am J Hum Genet. 2015-8-6

[8]
Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans.

Science. 2015-5-8

[9]
Developing medicines that mimic the natural successes of the human genome: lessons from NPC1L1, HMGCR, PCSK9, APOC3, and CETP.

J Am Coll Cardiol. 2015-4-21

[10]
Large-scale whole-genome sequencing of the Icelandic population.

Nat Genet. 2015-3-25

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索