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Researchers unlock disease information hidden in genome's control circuitry
Date:9/5/2012

Researchers at the University of Washington have determined that the majority of genetic changes associated with more than 400 common diseases and clinical traits affect the genome's regulatory circuitry. These are the regions of DNA that contain instructions dictating when and where genes are switched on or off. Most of these changes affect circuits that are active during early human development, when body tissues are most vulnerable.

By creating extensive blueprints of the control circuitry, the research also exposed previously hidden connections between different diseases. These connections may explain common clinical features, as well as offer a new approach for pinpointing the specific types of cells and tissues that either cause or are most affected by a particular disease. The findings provide a major paradigm shift for understanding the genetic causes of disease, and open new avenues for development of diagnostics and treatments. The findings appear in the Sept. 5 online issue of Science.

"Genes occupy only a tiny fraction of the genome, and most efforts to map the genetic causes of disease were frustrated by signals that pointed away from genes. Now we know that these efforts were not in vain, and that the signals were in fact pointing to the genome's 'operating system' -- the instructions for which are hidden in millions of locations around the genome," said Dr. John A. Stamatoyannopoulos, associate professor of genome sciences and medicine at the UW. "The findings provide a new lens through which to view the role of genetics and genome function in disease."

The human genome's control circuitry is encoded in millions of regulatory regions -- short DNA sequences that are scattered throughout the 98 percent of the genome that does not specify the protein product of a gene. Specialized proteins, called regulatory factors, recognize specific DNA sequences in these regulatory regions, thereby creating switches
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Contact: Leila Gray
leilag@uw.edu
206-543-3620
University of Washington
Source:Eurekalert  

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