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Gene that makes people 'early to bed and early to rise' demystified

The recent discovery that a mutant "clock" gene made some people "early to bed and early to rise," a condition known as familial advanced sleep phase syndrome (FASPS), offered one of the first glimpses into the genetic basis of sleep in humans. Now, researchers report in the Jan. 12, 2007 issue of the journal Cell, published by Cell Press, new evidence that helps to explain just how their bodies' natural alarm clocks get set to such an early wake-up time.

In studies of mice carrying the human FASPS gene, the researchers found that the mutant version of the Period 2 (Per2) clock gene--which is crucial for resetting the body's central clock in response to light--cannot be chemically modified by another enzyme that controls it. That failure leads to a reduction in the number of copies of the Per2 "message," and the characteristic shifted sleep pattern.

Eventually, such insight into the factors influencing people's so-called circadian, or daily, rhythm might lead to therapies that could adjust the body's clock in those suffering from conditions including jet lag or shift work sleep disorder, according to the researchers.

"This study highlights the power of natural human mutations to uncover things [about the circadian clock] that we might not otherwise have learned, or that we might have misunderstood before," said Howard Hughes Investigator Louis Ptácek, of the University of California, San Francisco.

"Most of the information we've had about these clock genes has been based on the Drosophila model and Per2 knockout mice," which lack the Per2 clock gene altogether, added study author Ying-Hui Fu, who is also at UCSF.

Based on those studies, "everybody had thought a short or long period depended on a change in protein stability," she said. "That's how we thought the system should work. But this paper shows that is not the case. It comes back instead to the transcription level as the most important step."

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Source:Cell Press


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