In This Article
- The Genome Aggregation Database (gnomAD) Consortium has outlined its first set of discoveries from an extensive database of exomes and genomes from populations around the world
- The gnomAD catalog provides the most comprehensive look into genes' sensitivity to variation and is a resource to support gene discovery in common and rare diseases
- The catalog has implications for improved diagnosis for rare genetic diseases and better evaluation of proposed drug targets in the future
The Genome Aggregation Database (gnomAD) Consortium has been working for the last 8 years to compile and study over 125,000 exomes and 15,000 whole genomes from populations around the world. Recent papers published in Nature, Nature Communications and Nature Medicine, gnomAD Consortium, with co-first and co-senior authors from Massachusetts General Hospital, outline the first set of discoveries from the database.
Konrad Karczewski, PhD, first author on the paper and computational biologist at Broad Institute and Massachusetts General Hospital's Analytic and Translational Genetics Unit, said the gnomAD catalog gives the best look so far at the spectrum of genes' sensitivity to variation and provides a resource to support gene discovery in diseases.
The flagship study, published in Nature, dramatically exceeds all previous catalogs in identifying loss-of-function (LoF) variants, which are genetic changes thought to disrupt the function of protein-coding genes. By comparing the number of these rare variants in each gene with a new model's prediction of their mutation rates, the researchers were able to determine how likely genes are to cause significant disease when distorted by mutations. The resulting classification scheme is able to predict which genes are likely to be involved in diseases such as intellectual disability.
Analyses from the seven papers unveil an expansive list of findings, which have implications for improved diagnosis for rare genetic diseases and better evaluation of proposed drug targets.
Michael Talkowski, PhD, of the Center for Genomic Medicine at Mass General, added that he has learned a great deal by building this catalog in gnomAD, but that they have clearly only scratched the surface of understanding the influence of genome structure on biology and disease.
Learn more about the Analytic and Translational Genetics Unit
Learn more about the Center for Genomic Medicine