Circadian Rhythms

A Family of Larks

Science's STKE  13 Feb 2001:
Vol. 2001, Issue 69, pp. tw7
DOI: 10.1126/stke.2001.69.tw7

Familial advanced sleep-phase syndrome is inherited autosomally. These individuals have unusual sleep cycles and wake up abnormally early each morning. In one such family, Toh et al. report that this characteristic is due to a single nucleotide mutation in the human Per2 homolog of the Drosophila period gene; this blocks phosphorylation by casein kinase I. In a satisfying parallel with studies in animals, a deficit in such phosphorylation shortens the animal's circadian period, because of altered function of PER in the molecular feedback loops that make up the circadian clock. This striking effect of a genetic polymorphism on human behavior paves the way to understanding the basis of human variation in daily rhythms.

K. L. Toh, C. R. Jones, Y. He, E. J. Eide, W. A Hinz, D. M. Virshup, L. J. Ptácek, Y.-H. Fu, An hPer2 phosphorylation site mutation in familial advanced sleep-phase syndrome. Science 291, 1040-1043 (2001). [Abstract] [Full Text]