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Last of known genes identified in complex obesity syndrome

By comparing three different species' genomes and adding some good old-fashioned genetic analysis, scientists have uncovered the identity of the last of eight genes known to contribute to Bardet-Biedl syndrome, a rare disorder characterized by a combination of some otherwise common problems, including obesity, learning difficulties, diabetes and asthma.

The identification of the BBS3 gene ends the search for primary BBS-causing genes in families studied for years by a team of scientists from the United States, Canada and the United Kingdom. However, the scientists are still hunting for other, less obvious genetic influences in these families.

Writing in the Aug. 15 advance online section of Nature Genetics, the international team reports that BBS3 is actually a gene formerly known as ARL6. Importantly, ARL6 is the first BBS culprit to belong to a family of genes and proteins with a known function, opening the door to figuring out what's really happening in people with the condition.

"We can use BBS3/ARL6 and its known function -- binding the molecule GTP -- as a great place to start to unravel the details of the other BBS proteins," says Nicholas Katsanis, Ph.D., assistant professor in Johns Hopkins' McKusick-Nathans Institute of Genetic Medicine. "And understanding BBS may provide important insight for understanding obesity, learning difficulties and other BBS-related problems that also appear in the general population."

Family studies had managed to link BBS3 to a region of chromosome 3, but getting to the gene had proven challenging. Now, by taking advantage of their recent discovery that faulty cellular structures called cilia are behind the problems seen in BBS patients, the researchers were able to zero in on the disease-causing gene.

Cilia are found on many different types of cells and can either act like antennae, sensing important signals, or help push fluid or mucous around, such as in the lungs. Some B
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
15-Aug-2004


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