• Home
  1. Home
  2. A systematic survey of loss-of-function variants in human protein-coding genes
Scientific article
OA Policy
English

A systematic survey of loss-of-function variants in human protein-coding genes

Contributors

MacArthur, Daniel G; Montgomery, Stephen; Dermitzakis, Emmanouil

Published in

Science, vol. 335, no. 6070, p. 823-828

Publication date

2012

Abstract

Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.

Keywords

  • Disease/genetics
  • Gene Expression
  • Gene Frequency
  • Genetic Variation
  • Genome, Human
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Proteins/genetics
  • Selection, Genetic

UNIGE affiliation entities

UNIGE research groups

Funding

  • Autre - Jeantet

Citation (ISO format)

MACARTHUR, Daniel G, MONTGOMERY, Stephen, DERMITZAKIS, Emmanouil. A systematic survey of loss-of-function variants in human protein-coding genes. In: Science, 2012, vol. 335, n° 6070, p. 823–828. doi: 10.1126/science.1215040

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0036-8075
1118views
1282downloads

Technical informations

Creation

15/12/2013 23:21:00

First validation

15/12/2013 23:21:00

Update

14/03/2023 20:43:31

Status update

14/03/2023 20:43:31

Last indexation

30/10/2024 15:23:17
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated