Analysis of protein-coding genetic variation in 60,706 humans
Monkol Lek, Konrad J. Karczewski, Daniel G. MacArthur · Exome Aggregation Consortium (ExAC); first authors Lek and Karczewski, senior/corresponding author Daniel G. MacArthur. Listed in Nature as Lek M, Karczewski KJ, Minikel EV, et al.
Summary
The Exome Aggregation Consortium (ExAC) aggregates and jointly analyzes high-quality exome sequencing data from 60,706 individuals of diverse ancestries, producing the largest catalogue of human protein-coding variation at the time. The dataset reveals roughly one variant per eight exonic bases and provides direct evidence of widespread mutational recurrence. It enables improved estimation of gene-level intolerance to loss-of-function variation and refines the interpretation of pathogenic variants in clinical genetics.
Key findings
- Catalogued protein-coding variation across 60,706 exomes, averaging about one variant every eight bases of the exome.
- Identified 3,230 genes nearly depleted of predicted protein-truncating variants, ~72% of which had no established disease phenotype.
- Provided evidence for widespread mutational recurrence and a resource that reclassified many previously reported pathogenic variants.
Subjects & keywords
Cite this paper
Monkol Lek, Konrad J. Karczewski, & Daniel G. MacArthur [Exome Aggregation Consortium (ExAC); first authors Lek and Karczewski, senior/corresponding author Daniel G. MacArthur. Listed in Nature as Lek M, Karczewski KJ, Minikel EV, et al.] (2016). Analysis of protein-coding genetic variation in 60,706 humans. Nature. https://doi.org/10.1038/nature19057
@article{lek2016analysis,
author = {Monkol Lek and Konrad J. Karczewski and Daniel G. MacArthur and {Exome Aggregation Consortium (ExAC); first authors Lek and Karczewski, senior/corresponding author Daniel G. MacArthur. Listed in Nature as Lek M, Karczewski KJ, Minikel EV, et al.}},
title = {Analysis of protein-coding genetic variation in 60,706 humans},
journal = {Nature},
year = {2016},
doi = {10.1038/nature19057},
url = {https://doi.org/10.1038/nature19057}
}