Brett Smith for redOrbit.com – Your Universe Online
Genetic mutations are thought to drive many autoimmune diseases in humans and a large international team of researchers has just identified 21 genetic variants that directly connect to different autoimmune diseases, according to a newly-published report in the journal Nature.
In the study, researchers used a complex mathematical tool to generate maps of various cell types that combine to foster disease-causing genetic variants.
“These findings give new insight into the cause of multiple sclerosis and other autoimmune diseases,” study author David A. Hafler, a professor of neurology and immunobiology at Yale, said in a recent statement.
For the study, scientists analyzed a wealth of information from 39 large-scale research endeavors called genome-wide association studies (GWAS). Groups of scientists in the past few years have performed GWAS, normally recruiting thousands of volunteers, to look at large blocks of DNA inside the human genome within which disease-causing genetic variants may exist. However, study of GWAS information to date has rarely indicated altered proteins, as remarkably few protein-encoding gene variants within these extensive swaths of DNA have been linked with the diseases being studied.
The study team noted that the genetic risks discovered via GWAS more frequently appear to be linked with DNA variants sitting outside of genes, fueling a notion that few medical benefits emerge from large-scale scientific studies of disease-causing genetic variation.
To unlock evidence of disease-causing variants, the scientists created software and used state-of-the-art sequencing methods to probe “epigenetic” characteristics of particular immune cells, in which there is gene activity without variations to the DNA sequence in the affected genes.
The study team found that relevant changes connected with autoimmune diseases take place in functional pieces of DNA known as “enhancers.”
While present within cells as long, stringy molecules, DNA can flex back onto itself with support from the chromosome’s structural proteins – which allows one component of DNA to connect to another. Enhancers fold in this manner to bind to DNA switches that turn genes on. Generally speaking, the enhancers recognized in the new study as playing a part in autoimmune disease were DNA series that did not go with DNA-sequence motifs thought to be vital to enhancers, and had not earlier been seen as possessing any functional purpose before, the researchers said.
“Once again, research is revealing new meaning in the world of DNA once thought of as junk — short, seemingly random DNA sequences that in fact serve meaningful roles in human physiology,” said study author Dr. Alex Marson, a genomics expert at the University of California, San Francisco.
“The genetic changes that cause autoimmune diseases are subtle. They rarely alter protein function and, as such, have been difficult to study,” added co-author Bradley Bernstein, a professor of pathology at Massachusetts General Hospital. “Here we combined new genetic and epigenetic methods to understand how these genetic changes alter immune function and cause disease.”
The researchers were also able to strongly connect the cause of MS to the immune system, and not a genetic source in the nervous system.
“This is highly consistent with the new multiple sclerosis treatments that work on the immune system, suggesting that we finally have a good handle as to the underlying causes of MS,” Hafler said.