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UCSF study offers insight into human circadian rhythms

particular family, the first report of a human circadian rhythm gene. (Science, Jan. 12, 2001).

The breadth of the knowledge coming out of the current study is somewhat unique, says Ptaceck. "I'm not aware of another study that has gone from the human to the fly to the mouse in a single study. It demonstrates of the combined power of human molecular genetics research and studies in animals."

The study began with the scientists isolating, or cloning, the mutant gene responsible for causing FASPS in five members of an extended family. The gene is known as casein kinase1 delta (ck1 delta); the mutated form is designated CK1 delta-T44A. They made the discovery by taking blood samples of the individuals and then using linkage analysis to hone in on the region of DNA within the chromosomes most likely to reveal the relevant gene, based on what was known about other genetic markers related to circadian rhythms. The gene was found on chromosome 17. (The mutated form was compared to the gene in family members who did not have FASPS.)

Next, they determined that, in a test tube, the activity of the enzyme (CK1 delta) encoded by the mutated gene was decreased.

Finally, to explore the effect of the genetic mutation on circadian activity, the scientists inserted the mutated human gene into the nerve cells of the circadian clock in the fruit fly Drosophila melanogaster and the mouse. Scientists have learned much about human gene function by studying animals, given the many genes that have been conserved through evolution, and both animals have been a key source of information regarding the genetic and molecular biology of circadian rhythms.

As expected, the transgenic mice displayed the same abnormal sleeping pattern seen in the human cases of FASPS, as measured in the decrease in their wheel-running activity.

Unexpectedly, however, the result was the opposite in the transgenic flies, as displayed by its extended locomotor activity.
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
30-Mar-2005


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