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Scientists get to the bottom of a big sheep mystery

By Tim Friend, USA Today

16 September 2002: After a 10-year search, scientists have found the gene that causes certain sheep to have big, muscular bottoms. The discovery may sound odd, but experts say it may shed new light on why some people seem destined to be obese while others are natural-born muscular speed skaters. More important, the method used to find the gene also could be used to locate genes for disorders such as autism, bipolar disorder and some cancers, says Randy Jirtle, professor of radiation oncology at Duke University in Durham, N.C.

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During fetal development, the big-bottom gene (called callipyge, Greek for ''beautiful buttocks'') shuts down production of fat cells. With few fat cells, energy is converted into bulky muscle. It is possible a disruption in the same gene or its region in humans could load a person with extra fat cells from birth.

The story of big-bottomed sheep began 20 years ago when a farmer observed a young ram in his flock growing muscular, oversized buttocks, a result of a naturally occurring mutation. He reasoned that if flocks of such sheep could be bred, they would yield more meat per animal. The ram was bred with normal females and, as predicted, they produced big-bottomed lambs, some of them females. But when the big-bottomed females were bred to normal rams: no big bottoms. That defied traditional patterns of inheritance, Jirtle says, but no one knew why.

Ten years ago, scientists began hunting for the big-bottom gene, but traditional methods found nothing. Finally, U.S. Department of Agriculture geneticist Brad Freking, who led this study, obtained DNA from inbred offspring of the original ram, decoded it and compared it with DNA from normal sheep. Among more than 450,000 letters of code, he found a single letter out of place; from that mutation, scientists tracked down the genes. Usually they find a gene first, then look for mutations.

The gene was invisible to standard gene-hunting methods because of the strange inheritance pattern observed 20 years ago. That complex and poorly understood pattern is called imprinting. Normally, people inherit two copies of their genes -- one from the mother, one from the father. That way, if one copy goes bad, the good copy can do the work. With imprinting, only one copy works to begin with; the other copy is essentially bound and gagged. A single mutation can completely knock out gene function.

Imprinting already is associated with at least three serious genetic disorders and is probably linked to many more, including autism, bipolar disorder, schizophrenia and Tourette's syndrome. Scientists have searched for genes for these disorders without any luck. If they start looking with imprinting in mind, the genes might be revealed. The same may hold true for cancer.

As for the big-bottomed sheep, all that muscle and no fat make the meat tough and dry. No one wants to buy them.

''All that meat and not a bite to eat,'' Jirtle laments.