Comparing 240 mammalian genomes helps geneticists identify disease mutations

Reviewed by Emily Henderson, B.Sc.November 11, 2020

A large international consortium led by scientists from Uppsala University and the Broad Institute of MIT and Harvard sequenced the genome of 130 mammals and analyzed the data along with 110 existing genomes to allow scientists to identify which locations are important in DNA. . This new information can help both research into disease mutations in humans and the best way to preserve endangered species. The study is published in Nature.

When scientists and doctors want to understand which mutations give rise to diseases such as cancer, heart disease or schizophrenia, they compare the genomes of many matched patients and controls. They often find tens to hundreds of regions that predispose to disease. These regions generally do not overlap the genes, but are located outside the genes and each region can contain hundreds of mutations among which it is difficult to identify the one predisposing to disease.

During evolution, most positions in DNA change many times at random. If a location has not changed in 100 million years (since the first mammal), it is very likely that that specific location has an important function in the genome. With the help of this concept, evolutionary constraint, it is much easier to find the regulatory elements that govern when, where and how much of a protein is made up of a gene.

Comparing the genomes of the 240 mammals will help geneticists identify mutations that lead to human disease. “

Professor Kerstin Lindblad-Toh of Uppsala University, SciLifeLab and Broad Institute of MIT and Harvard

In addition to understanding the human genome, all of these genomes together, sampled extensively among mammals, can be used to study how specific species adapt to different environments. For example, some otters have thick, water-resistant coats and some mice, but not all, have adapted to hibernation. These animal traits can help us understand human traits such as metabolic diseases.

With climate change and more animal habitats influenced by human activities, it becomes increasingly important to defend endangered species. Traditionally, scientists study many individuals in different populations of a species to understand the genetic diversity that exists in it. This is important in understanding how to protect specific species. In this study, animals on the IUCN (International Union for Conservation of Nature) Red List of Endangered Species had less variation in their genome, which is consistent with their endangered status.

“We hope that our extensive dataset, available to all scientists around the world, will be used to understand disease genetics and biodiversity protection,” says Lindblad-Toh.