Scientists on Wednesday unveiled patterns in the largest catalogue of human genetic variation yet assembled, highlighting mutations mistakenly blamed for causing rare diseases and others that may play an unexpected role in ill health.
Diving deep into the human gene pool, a 100-strong team of researchers two years ago built a library of more than 10 million variants in exomes. These are a small part of the human genome, accounting for no more than 2% of DNA, but are crucially important.
Exomes consist of the coding portions of genes – the stretches of DNA that express proteins, the basic building blocks of the human body and its functions. Flaws can have a cascade effect, leading to disease.
A study, published in the journal Nature, is the first analysis of the database – and confirms a rich potential for pinpointing inherited causes of disease. The new resource “is invaluable”, said senior author Daniel MacArthur, co-director of medical and population genetics at the Broad Institute of MIT and Harvard.
“It gives us the ability to discover rare variants and offers an unparalleled window into the roots of rare genetic diseases.” Most genetic variations – people each have tens of thousands – are benign.
But without a near-complete library of the possible permutations of human DNA, it is very hard for scientists, or doctors treating patients, to pick out the harmful ones and link them to specific conditions. The Exome Aggregation Consortium database, compiled from dozens of previous studies, seeks to fill this gap. It includes detailed profiles of the protein-coding genes from more than 60 000 people.
“The goal was to create a dataset that could be used as a reference for the variation present in the general population,” MacArthur said. “Physicians can look up a genetic variation found in their patients and understand how common it is.”