Three studies published in Nature have mapped how DNA variations affect gene activity in individual immune cells, helping explain how some genetic differences may contribute to disease. The research links risk-associated variants to specific cell types and biological processes, and could help guide the development of targeted therapies.
The studies were carried out by researchers from Australia’s Garvan Institute of Medical Research, Murdoch Children’s Research Institute and the University of New South Wales as part of the TenK10K project. They sequenced the genomes of nearly 2,000 people and measured gene activity in almost five million immune cells, using single-cell sequencing to examine patterns at an unusually detailed scale.
The analyses connected genetic risk regions for 16 autoimmune, neurological and cancer-related diseases with different forms of gene regulation in immune cells. Researchers identified nearly 1,500 genes that may contribute to disease, including genes whose effects appear limited to particular immune cell types.
One example involved a genetic variant that increases activity of the OSM gene in natural killer cells and is associated with a higher risk of irritable bowel syndrome. Joseph Powell, who took part in all three studies, said the finding pointed to a specific immune pathway that could potentially be explored as a target for future treatment.
By tracing links from genetic variants to their effects in particular cells and the mechanisms involved, the studies go beyond simply associating DNA differences with disease risk. The researchers say this understanding could help identify new drug targets and, in time, indicate which patients are more likely to respond to a treatment based on their genetic and cellular profiles.
Sources: Focus.it.