Understanding genetics, treating diabetes; UCSF researcher gets to the roots of autoimmune disease

Alex Marson

Understanding genetics, treating diabetes

UCSF researcher gets to the roots of autoimmune disease

BY KATHLEEN JAY, UCSF Diabetes Center

This week, UCSF researcher Alex Marson, MD/PhD, and his research team published findings that may speed up treatment for autoimmune diseases, such as diabetes, multiple sclerosis and Crohn’s disease. Published in the journal Nature, Marson's paper -- entitled "Genetic and epigenetic fine-mapping of causal autoimmune disease variants" -- identifies a new method for determining the genetic changes that may contribute to autoimmune diseases.

"Our approach identifies causal risk genetic variants for 21 autoimmune diseases, such as diabetes, multiple sclerosis and Crohn’s disease," Marson, a physician who also runs a research lab at the UCSF Diabetes Center, said. "Our hope is that the same technique could be used to help unravel the causes of other complex disorders."

Large-scale genetic studies have previously highlighted hundreds of areas in the genetic code that are linked to autoimmune disease; however, these regions are peppered with multiple base-pair changes, making it hard to work out which are the crucial, disease-causing mutations.

Marson, his research team, and colleagues at the Broad Institute at the Massachusetts Institute of Technology and Harvard, have developed a new algorithm that enables these candidate-causal variants to be teased out.

"The algorithm is very powerful because it incorporates genetic changes -- whereby the DNA sequence is altered -- as well as certain epigenetic influences, which alter gene activity but not the DNA sequence," Marson said.

The study -- which reveals that the most-causal variants are located in genetic regions that do not code for proteins -- suggests that these variants generate their effects through other, unknown mechanisms that affect immune cell function.

"Disease risk tends to be linked to variations in cell-type-specific enhancers involved in the stimulation of immune cells," Marson said. "By taking a genetic approach to studying these variations, our goal is to getting closer to finding a cure for diabetes."

"Alex Marson and his team represent the innovative thinking of the UCSF Diabetes Center," Matthias Hebrok, PhD and director of the Center, said. "His ground-breaking research in genomic research will provide novel clues regarding the defects underlying autoimmune diseases. His work provides novel information for other Diabetes Center investigators to get us closer towards finding a cure for diabetes."

For more information, visit http://diabetes.ucsf.edu.

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