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Bah-uns of Steel - Muscular sheep have gene mutation that banishes fat

By Serena Gordon, Health Scout News

16 September 2002: How would you like to eat whatever you want, and have your body convert almost all of it directly to muscle?

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No problem -- as long as you're a callipyge (cal-ah-PEEJ) sheep. Humans, sadly, will have to wait awhile.

After more than 10 years of searching, scientists have discovered the mutated gene that causes callipyge (which means beautiful buttocks) sheep to have large, muscular rear ends.

This discovery has scientists excited for several reasons. First, they hope that by studying the mutation, they can learn more about how muscle and fat are deposited in the sheep, which might provide clues to how fat and muscle are metabolized in humans. They're also excited because it's given them a whole new way to search for elusive gene defects. Their findings appear in the October issue of Genome Research.

It all started 20 years ago when a Nebraska farmer noticed one of his sheep had a very muscular bottom. "Callipyge sheep are like Arnold Schwarzenegger. They have huge muscles with virtually no fat," says one of the researchers, Randy Jirtle, a professor of radiation oncology at Duke University Medical Center. The animals convert food into muscle 30 percent more efficiently than normal sheep do, he says.

Once the farmer started breeding the sheep, he noticed that only those born to large-bottomed males carried the unusual trait. Because of this, scientists knew they were searching for an imprinted gene -- rare genes that are literally stamped with markings that turn off one parent's gene. Normally, two copies of each gene are inherited -- one from the mother and one from the father. One copy will be dominant and the other recessive, but both will be present. This isn't so with imprinted genes.

Jirtle, along with Brad Freking, a geneticist with the U.S. Department of Agriculture, and their colleagues searched through all of the known genes and turned up nothing that could be responsible for the muscular mutation. Then Freking and his team compared DNA from normal sheep to DNA from the large-bottomed callipyge.

They found 600 distinct markers, which are minute variations, in the gene sequence they examined. Only one, however, was unique to callipyge sheep. What was truly unusual, says Jirtle, is that they found this marker in an area scientists had thought contained no genes, and that such a minor mutation could have such a dramatic effect.

Jirtle says this is the first time scientists have identified a gene through its mutation. Usually, scientists look for genes, and only after a gene is identified do they start searching for its mutations.

This new method of searching for genetic mutations may help scientists solve the mystery of certain disorders, such as autism or bipolar disorder, Jirtle says. By comparing gene sequences in people who have the disorder to people who don't, researchers may be able to zero in on where the mutation is occurring.

"So, we're at the end of the beginning," explains Jirtle, who says the researchers now hope to figure out how this gene causes the change in metabolism, which could ultimately be important in treating obesity.

"[This study] is intriguing from several points of view," says Dr. Richard Re, director of research for the Ochsner Clinic Foundation in New Orleans. "The methodology appears to be atypical, and the sheep have a very interesting system for fat-muscle balance." However, he says it's too soon to know what impact this discovery might have on obesity research in the future.

What To Do

This article from the Harvard University Gazette and this one from the Medical College of Wisconsin look at ways genes may affect human obesity.

SOURCES: Randy Jirtle, Ph.D., Professor, Radiation Oncology, Duke University Medical Center, Durham, N.C., Richard Re, M.D., director, research, Ochsner Clinic Foundation, New Orleans; October 2002 Genome Research

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