Called imprinted genes because they are literally stamped with markings that inactivate one parent's copy, such genes are quite rare and unusual in the way they operate. They often work only in specific tissues and at defined intervals during an animal's development, said Susan Murphy, Ph.D., a Duke University Medical Center co-author.
"Finding imprinted genes can depend on when and where in the body you search for them," said Murphy. "If you look for an imprinted gene in a mature animal when that gene is only expressed during fetal development, then you may miss it entirely."
The researchers sought an imprinted gene because the big-bottomed sheep inherited a functional copy of the mutated gene from their father alone -- the mother's copy is turned off. Silencing of one parental copy is characteristic of imprinted genes.
For 10 years, the researchers searched likely regions where the callipyge gene and its mutation might reside; namely, in known genes on sheep chromosome 18, according to previous research. But their efforts turned up intact genes with no mutations. Finally, the team of researchers tried a novel approach.
They compared a specific DNA sequence from inbred offspring of the original big-bottomed sheep against the DNA of normal sheep to look for minute genetic variations, called "markers." While they found 600 distinct "markers," only one was unique to the callipyge sheep: a single base change from A to G in the DNA sequence. Further testing showed this mutation alone clearly gave rise to the sheep's big-bottom stature.
Yet the mutation appeared to reside in a "gene desert," where no known gene had previously been mapped, said Freking. Interestingly, when they compared this sequence in the sheep to the same region of humans and mice, they found that the DNA sequences surrounding the callipyge mutation were highly similar in all three species.
"The more similar the region, the more l
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Contact: Rebecca Levine
levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
16-Sep-2002