Rare gene variants linked to inflammatory bowel disease

October 10, 2011

(Medical Xpress) -- An international team of scientists, including researchers from Karolinska Institutet, have identified several rare gene variants that predispose to IBD (Inflammatory Bowel Disease). The study provides new insights into disease pathogenesis, and suggests next-generation sequencing may speed hoped-for personalized treatment of common complex disorders.

Common chronic diseases such as , hypertension, obesity, diabetes, asthma, rheumatoid arthritis, inflammatory bowel disease and many others show , and hundreds of have been recently identified. DNA variants associated with modestly increased risk can be frequently found in the general population, but the pathogenetic relevance of rare genetic changes is often unknown in these complex disorders.

Accurate sequencing of the entire has become feasible with the recent advent of next-generation sequencing, and a large International team of scientists, including researchers from Karolinska Institutet, have now used this approach to seek for rare DNA variants in 56 genes known to predispose to Crohn's disease (CD), one of the two major forms of IBD together with ulcerative colitis. In their study, the genomic regions containing these genes have been re-sequenced in 350 Crohn's disease patients and 350 healthy controls, and several newly identified rare variants further tested for their risk effects in 16054 Crohn's disease patients, 12153 ulcerative colitis patients and 17575 controls from different countries.

"The results suggest that, even in the same gene, rare and common DNA variants are both important in determining one's risk to , with rare variants possibly more deleterious", says Associate Professor Mauro D'Amato at the Department of Biosciences and Nutrition, Karolinska Institutet, who led the Swedish part of the investigation. "This observation, should it become commonplace in complex diseases, may mean additional variants are to be routinely searched for in individual patients. With the cost of human genome sequencing rapidly decreasing, we should be well equipped for future clinical applications and improved diagnostics."

Crohn's disease and ulcerative colitis manifest as chronic inflammation of the gastrointestinal tract, with life-long symptoms including abdominal pain, diarrhea, rectal bleeding, ulcers, weight loss and debility. More than 1% of the general population is affected, there is currently no cure and surgery is often necessary in the most severe cases.

The study was published in the top-ranking journal Nature Genetics, and stems from an International collaboration of several laboratories in Europe and USA, and the contribution of the International IBD Genetic Consortium (IIBDGC). Corresponding authors are Dr Manuel Rivas and Associate Professor Mark Daly from the Broad Institute of Harvard and MIT in the US.

Explore further: New genetic markers for ulcerative colitis identified

More information: Rivas MA, Beaudoin M, Gardet A, et al., Nature Genetics (2011) online 9 October.

Related Stories

New genetic markers for ulcerative colitis identified

January 4, 2009

An international team led by University of Pittsburgh School of Medicine researchers has identified genetic markers associated with risk for ulcerative colitis. The findings, which appear today as an advance online publication ...

Research team identifies genes linked to ulcerative colitis

March 17, 2010

A study of the human genome led by Cedars-Sinai researchers has now identified genes linked to ulcerative colitis, offering clues as to what causes the condition and potential avenues for new therapies to treat the disease.

30 new gene variants linked to Crohn's disease

November 22, 2010

An international team of scientists, including researchers from Karolinska Institutet, Sweden, have found 30 new gene variants associated with the risk of Crohns disease. The results of the study provide valuable insight ...

The heritability of Crohn's disease better understood

December 17, 2010

A University of Liege GIGA-Research Unit team has discovered new particular genetic mutations which influence hereditary predisposition to Crohn's disease, a chronic inflammatory disease of the bowel. The rare variants discovered ...

Recommended for you

Stop the rogue ADAM gene and you stop asthma

July 21, 2016

Scientists at the University of Southampton have discovered a potential and novel way of preventing asthma at the origin of the disease, a finding that could challenge the current understanding of the condition.

Scientists reveal cellular clockwork underlying inflammation

August 27, 2015

Researchers at the Virginia Bioinformatics Institute at Virginia Tech have uncovered key cellular functions that help regulate inflammation—a discovery that could have important implications for the treatment of allergies, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.