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Analysis of protein-coding genetic variation in 60,706 humans
- Source :
- Lek, M, Karczewski, K J, Minikel, E V, Samocha, K E, Posthuma, D & Exome Aggregation Consortium, U 2016, ' Analysis of protein-coding genetic variation in 60,706 humans ', Nature, vol. 536, no. 7616, pp. 285-291 . https://doi.org/10.1038/nature19057, Nature, 536(7616), 285-291. Nature Publishing Group, Nature, vol 536, iss 7616
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- SummaryLarge-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) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). The resulting 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 show that this catalogue can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 72% of which have 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.
- Subjects :
- 0301 basic medicine
Proteome
DNA Mutational Analysis
Datasets as Topic
Human genetic variation
GUIDELINES
0302 clinical medicine
Exome Aggregation Consortium
SEQUENCE VARIANTS
Coding region
2.1 Biological and endogenous factors
Exome
Aetiology
MUTATION
Genetics
0303 health sciences
Multidisciplinary
HUMAN-DISEASE
NETWORKS
Multidisciplinary Sciences
Phenotype
Mutation (genetic algorithm)
Science & Technology - Other Topics
Biotechnology
General Science & Technology
Genomics
Computational biology
Biology
DNA sequencing
03 medical and health sciences
Rare Diseases
Clinical Research
Genetic variation
Humans
Genetic Testing
Gene
030304 developmental biology
Science & Technology
Human Genome
HUMAN-POPULATION HISTORY
Genetic Variation
FRAMEWORK
R1
EVOLUTION
030104 developmental biology
DISCOVERY
Sample Size
Generic health relevance
3111 Biomedicine
Genètica humana -- Variació
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Database :
- OpenAIRE
- Journal :
- Lek, M, Karczewski, K J, Minikel, E V, Samocha, K E, Posthuma, D & Exome Aggregation Consortium, U 2016, ' Analysis of protein-coding genetic variation in 60,706 humans ', Nature, vol. 536, no. 7616, pp. 285-291 . https://doi.org/10.1038/nature19057, Nature, 536(7616), 285-291. Nature Publishing Group, Nature, vol 536, iss 7616
- Accession number :
- edsair.doi.dedup.....d62da66cab8b3012619459d5ee3a67d5