Press Release

Department of Human Genetics
Eccles Institute of Human Genetics
University of Utah

RELEASE DATE: 30 Aug. 1999

contact:
Connie Barth -- (801) 585-6135
Louis J. Ptacek, M.D. -- 801-581-3993

SALT LAKE CITY, Utah -- Most of us rise, sleep, work, and play as directed by our biological clocks, which fit nicely into a 24-hour day. A few people live with a drastically different schedule dictated by their genes. Researchers at the University of Utah have identified the first-known inherited disorder of human circadian rhythms, or biological clocks, thus offering a glimpse into our clockworks.

In Nature Medicine’s September 1999 issue, Howard Hughes Medical Institute Investigator Louis Ptácek and neurologist Christopher Jones describe their study of three families with an unusual sleep pattern, called familial advanced sleep-phase syndrome (FASPS), which is an inherited form of a more common sleep disorder.

Although such conditions were predicted based on studies of circadian rhythm mutations in mice and fruit flies, this study is the first to identify such a variation in a human circadian rhythm. "The significance of this research is in moving from the fly and the mouse to the human," says Ptácek.

Once the gene responsible for FASPS is isolated and cloned, work currently being pursued by Ptácek and Jones, its role in the biological processes directed by circadian rhythms can be determined.

It’s been 28 years since the first circadian rhythm mutation was identified: a fruit fly with a longer-than-normal clock period. Human mutations have been much harder to identify because circadian rhythms are thought to be determined by a complex mix of genetics and environment. Sleeping patterns, for example, vary within a normal range, with some people preferring mornings and some preferring evenings.

FASPS, on the other hand, overrides socio-cultural norms. Persons with this disorder tend to go to bed and get up 3-4 hours earlier than someone with a more typical clock. The length of a day, according to their clock, is less than 24 hours. Thus, for people with FASPS, 6 p.m. is the biological equivalent of 10 p.m. Individuals with FASPS get up as early as 1 a.m. to a world they describe as "cold, dark, and lonely," says Ptácek. To adjust their schedule to a 24 hour day is much more difficult than for someone with a typical clock.

Treatments for FASPS, although it is not necessarily debilitating, are only a small part of the possible implications of this research. "We can think of major disasters, such as Three Mile Island, where a conflict of sleep patterns and work schedules may have contributed to the accident. But we can also think of everyday problems such as traffic accidents and insomnia. Even school schedules can be difficult for children who can’t get up early in the morning," Ptácek notes. His team aims to first identify the gene for FASPS, then use it to develop a broader understanding of the workings of the biological clock.

Research on FASPS was conducted at the University of Utah Eccles Institute of Human Genetics, the Sleep Disorders Center and the General Clinical Research Center, and at Cornell University. Research was funded in part by a grant from the National Institutes of Health.