Press Release

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

RELEASE DATE: 4 Jan. 2001

contact:
Connie Barth -- (801) 585-6135

SALT LAKE CITY, Utah -- Jan. 4 -- Last year’s finding by University of Utah scientists of an unusual, inherited sleep pattern in humans received wide notice as the first-known human circadian rhythm disorder. An expanded research team has now found the genetic cause and a possible biochemical mechanism for Familial Advanced Sleep-Phase Syndrome (FASPS), the first human behavior with a clear genetic cause for which a gene has been identified. The study is to be published in the February 2 edition of the journal Science.

FASPS is not really a disease, per se, but a strikingly different sleep pattern caused by a single, dominant gene. Persons with FASPS have a faster biological clock that makes them feel sleepy at 7 p.m. and ready to wake up at 2 a.m. The discovery of the FASPS gene represents a landmark in behavioral genetics. Previous reports on FASPS discussed possible medical applications of this research, including treatments for ASPS, a non-inherited sleep disorder that affects one third of elderly people, and for individuals with jet-lag and who work graveyard shifts. Identification of a genetic cause for our sleep patterns is also a societal issue that may necessitate changes in public policy or established schedules such as school schedules.

Identification of human behavior genes is usually more complex than disease genes because of the difficulty of identifying and classifying human behaviors. While diagnosing individuals with a certain disease can be a straightforward process, identifying clear-cut categories of human behavior -- such as one’s tendency to get up early -- is not. "Human behaviors are more susceptible to changes caused by our environment than are diseases," says Ying-Hui Fu, Ph.D., a lead author of the study.

To address this complication, Fu’s colleague Dr. Christopher Jones used a well-established medical method for categorizing the patients in the study as either "morning larks" or "night owls" on a numeric scale. This classification enabled Fu and neurologist Louis Ptácek, M.D., to search for shared gene mutations in affected individuals.

The gene search was aided by data from the Drosophila (fruit fly) genome sequencing project, a part of the Human Genome Project. Other researchers had previously identified genes in Drosophila that caused circadian rhythm disorders, so Fu and Ptácek were interested to see whether mutations in a corresponding human gene caused FASPS. They found that to be the case: the human gene that causes FASPS, named per2, is similar to the Period gene in Drosophila, which was the first gene to be discovered with an effect on the circadian rhythm in any animal.

Examination of the gene sequence of the mutated per2 showed a simple point mutation that caused a glycine amino acid -- a small, uncharged molecule -- to be substituted for a serine amino acid -- a larger and more reactive molecule -- in the per2 protein. Along with collaborator Dr. David Virshup, Fu and Ptácek examined the biochemical consequences of the FASPS mutation and are now investigating how this change creates a disruption in human circadian rhythms.

Ying-Hui Fu, Ph.D., is an associate professor of Neurobiology and Anatomy and a researcher in the Eccles Institute of Human Genetics. Louis Ptácek, M.D., is an associate professor of Neurology and Human Genetics and an investigator with the Howard Hughes Medical Institute. Christopher Jones, M.D., is with the University Hospital Sleep Disorders Center and David Virshup, M.D. is with the Huntsman Cancer Institute’s Center for Children. This work was funded in part by the National Institute of Health, the National Center for Research Resources, and the Howard Hughes Medical Institute.