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Mapping heart disease

Researchers uncover genes that may dramatically affect heart health

Though heart disease is a major cause of disability and death, very little is understood about its genetic underpinnings.

Recently, an international team of investigators at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Sanford-Burnham Medical Research Institute (Sanford-Burnham) and other organizations shed new light on the subject.

Studying Drosophila (fruit flies), the team investigated 7061 genes and built a detailed map that shows how a portion of these genes contribute to heart function and disease. Importantly, the researchers identified many genes that had not previously been associated with heart disease. The research is being published as the cover story in the April 2 issue of Cell.

Using RNAi technology—which selectively knocks out genes so researchers can study their function—the team found nearly 500 genes that when inhibited cause flies to experience heart problems while under stress. In particular, the team found that a protein complex called CCR4-Not has a role in heart function. Turning off CCR4-Not complex genes caused heart muscle abnormalities (cardiomyopathies) in both flies and mice. These findings provide new insights into human health, as a common mutation in the human NOT3 gene is associated with a heart condition that often leads to lethal arrhythmias or sudden cardiac death.

"Our work on flies has identified a possible cause of human heart disease that the human genetic screens had missed," said co-lead researcher Dr. Josef Penninger, of IMBA.

The creation of this genetic map is only the beginning. The researchers identified many genes with no known function that may, when malfunctioning, predispose humans to heart disease. Much work needs to be done to determine the mechanisms by which these genes influence heart health.

"We already established that genes responsible for making the heart in fruit flies have a similar role in humans; and now we find that many of the genes that help the heart maintain normal function also prevent heart disease in humans," said co-lead researcher Rolf Bodmer, Ph.D., director of the Development and Aging program at Sanford-Burnham.

This international team included lead scientists from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (Vienna, Austria), Sanford-Burnham Medical Research Institute and Akita University (Japan). They were assisted by researchers at Tokyo Medical and Dental University, Toronto General Hospital, Keio University School of Medicine (Japan), Strand Life Sciences (Bangalore, India), New York University, Institute of Human Genetics (Munich, Germany), General Central Hospital (Bolzano, Italy) and the University of Lübeck (Germany).

About Sanford-Burnham Medical Research Institute

Sanford-Burnham Medical Research Institute (formerly Burnham Institute for Medical Research) is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.

Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation.

Josh Baxt | EurekAlert!
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