Study of Mysterious Auto-Immune Diseases

| October 31, 2014 | 0 Comments | Email This Post Email This Post

In autoimmune diseases affecting millions, researchers pinpoint genetic risks, cellular culprits

Scores of autoimmune diseases afflicting one in 12 Americans — ranging from type 1 diabetes, to multiple sclerosis (MS), to rheumatoid arthritis, to asthma — mysteriously cause the immune system to harm tissues within our own bodies. Now, a new study pinpoints the complex genetic origins for many of these diseases, a discovery that may lead to better diagnosis and ultimately to improved treatments.

A team of scientists from UC San Francisco, the Broad Institute of MIT and Harvard, and Yale School of Medicine developed a new mathematical tool to more deeply probe existing DNA databases. In so doing they discovered how certain DNA variations, when inherited, are likely to contribute to disease.

By applying their method to analyzing data from previous studies of 21 different autoimmune diseases, the research team has deepened scientific understanding of the genetic underpinnings of a wide range of these disorders. They also found the specific immune cells most responsible for the diseases. Their study is published online on October 29, 2014 in Nature.

The researchers examined a wealth of data from 39 large-scale studies called genome-wide association studies (GWAS). Teams of scientists in recent years have conducted GWAS — typically enlisting thousands of study participants — to identify large blocks of DNA within the human genome within which genetic variants are implicated as risk factors for common diseases. But examination of GWAS data to date has seldom pointed to altered proteins, as surprisingly few protein-encoding gene variants within these broad swaths of DNA have been associated with the diseases under investigation.

Instead, the genetic risks identified through GWAS more often appear to be associated with DNA variations that do not reside within genes. The nature of this risk has defied understanding until now, fueling a perception that few medical benefits have thus far emerged from large-scale studies of human genetic variation being conducted in the wake of the initial Human Genome Project.

Instead, the genetic risks identified through GWAS more often appear to be associated with DNA variations that do not reside within genes. The nature of this risk has defied understanding until now, fueling a perception that few medical benefits have thus far emerged from large-scale studies of human genetic variation being conducted in the wake of the initial Human Genome Project.

In the new study the researchers found that the presence of specific genetic variants in different autoimmune diseases can alter patterns of activity of genes in particular ways that affect functions of the immune system. This was true despite the fact that the genetic variants are not within genes.   Study of Mysterious Auto-Immune Disease

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