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Researchers identify cause of 'early bird' sleep disorder

A few rare people who consistently nod off early, then wake up wide-eyed much before dawn, can blame a newly-found mutant gene for their sleep troubles, Howard Hughes Medical Institute researchers announced today.

This odd "time-shift" trait -- called familial advanced sleep phase syndrome (FASPS) -- was studied in one affected family by neurologist Louis J. Ptacek, a Howard Hughes Medical Institute researcher, and Ying-Hui Fu, at the University of California, San Francisco. Their report appears in the March 31, 2005, issue of the journal Nature.

The sleep-shifting mutation they found is in "a gene that was not previously shown in mammals to be a circadian rhythm gene," Ptacek explained. It's not yet clear how the mutant gene works to shift people's sleep time, their circadian rhythm, he added. But follow-on experiments in fruit flies and mice yielded results that are intriguing.

When the mutant gene was inserted into the flies, for example, it did the opposite of what was seen in the human family: it lengthened circadian rhythm. Yet in genetically engineered mice, the same gene change made the mice early risers -- mimicking what was seen in humans with FASPS.

So, studies of all three organisms -- flies, mice and humans -- "will help us understand the similarities and differences" in how the gene works in different settings, in different genetic backgrounds, he said. Experiments can be done in mice and flies, with results applying to humans, while the studies of humans can inform what's being seen in the flies and mice.

In addition, "these results show that the gene is a central component of the mammalian circadian clock, and suggest that mammalian and fly clocks may have different regulatory mechanisms, despite the highly conserved nature of their individual components," the research team wrote in Nature. Such studies may help unravel some of the fundamental mysteries of how circadian rhythms are established and maintained in creatures that
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
30-Mar-2005


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