A collection of research articles and related content from the gnomAD Consortium describing and analysing human genetic variation.
The human genome comprises both our protein-coding genes and the regulatory information that controls when, and to what extent, those genes are expressed. While humans mostly share the same repertoire of genes and regulatory elements, the underlying sequences are as diverse as the people on Earth; each individual’s genome is unique. To reflect this diversity and to capture the extent of variation among a large group of individuals on an unprecedented scale, the Genome Aggregation Database (gnomAD) has aggregated 15,708 whole genomes and 125,748 exomes (the protein-coding part of the genome). Analyses of this rich resource have created a catalogue of the different types of variation present, and revealed their potential functional impact and how this information could help to identify disease-causing mutations and to prioritize potential drug targets.
This collection showcases articles from the gnomAD consortium describing and analysing the spectrum of genetic variation across this dataset, including an editorial and News & Views.
gnomAD at a glance
A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.
Analysis of predicted loss-of-function variants from 125,748 human exomes and 15,708 whole genomes in the Genome Aggregation Database (gnomAD) provides a roadmap for human ‘knockout’ studies and a guide for future research into disease biology and drug-target selection.
A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.
A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.
Analysis of large genomic datasets, including gnomAD, reveals that partial LRRK2 loss of function is not strongly associated with diseases, serving as an example of how human genetics can be leveraged for target validation in drug discovery.
Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.
Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.
Landmark study identifies the genes that it seems people can and cannot live without and highlights ongoing challenges in making data sets more representative of the world’s population.
A massive genome-sequencing and analysis effort has produced the most comprehensive sets of data and tools for understanding human genetic variation so far. The resource will be invaluable to biologists of every stripe.