UA's Arizona Respiratory Center Receives $250,000 Grant to Study Genetic Basis of Circadian Rhythm Sleep Disorders

August 2004/Vol. 20 / No. 6

UA's Arizona Respiratory Center Receives $250,000 Grant to Study
Genetic Basis of Circadian Rhythm Sleep Disorders

You probably know "night owls," people not ready to fall asleep until the wee hours of the morning. And, you may know "larks," early risers who wake before the sun comes up and are ready for bed right after dinner. People with extremely early or extremely late sleep times may suffer from Circadian Rhythm Sleep Disorder (CRSD).

In CRSD a person's circadian system makes it difficult for them to sleep at the time they wish to schedule. A prevalent condition, CRSD often results in diminished quality of life, depression, impaired health and a greater risk of having accidents.

There is evidence to indicate that CRSD is under genetic control, as approximately 50 percent of the people with this disorder have close family members with a similar trait. Yet, little is known about the nature and prevalence of the changes in DNA sequence that are responsible for the inheritable component of this condition.

With a $250,000 grant-assist from the National Institutes of Health (NIH), researchers at the Arizona Respiratory Center are collaborating with scientists at the University of California in San Diego (UCSD) to systematically study the genetic variants associated with this disorder. In the first phase of this three-year study, researchers at UCSD, under the direction of Daniel Kripke, MD, professor of psychiatry, will recruit 200 participants with delayed sleep phase systems, "night owls." Once a participant has met all of the clinical criteria, a small blood sample will be drawn and DNA preserved for future testing. This sample will be shipped to the Arizona Respiratory Center for analysis.

Photo by Martha Lochert
Dr. Walt Klimecki adjusts one of the robots in the Analytical Genetics Lab at the Arizona Respiratory Center. His laboratory processes tens of thousands of genetic tests per day.

Genetic analysis aimed at determining which of the nearly 30,000 human genes are responsible for the inherited component of CRSD will be conducted at the Analytical Genetics Laboratory (AGL) at the Arizona Respiratory Center, under the direction of Walt Klimecki, DVM, PhD, assistant research professor of medicine.

"Remarkable breakthroughs in our understanding of the cell biology that controls circadian rhythm make the circadian control system an outstanding model for studying how naturally occurring variation in DNA sequence among people can dramatically alter something as basic as sleep scheduling," says Dr. Klimecki.

"This project underscores the value of state-of-the-art, genomics laboratories, not only to the University of Arizona, but to the larger scientific community. While Dr. Kripke's group is world-renowned for its clinical studies of sleep disorders, it did not have the capability to conduct a large-scale genetics study. The Analytical Genetics Lab, unique at the University of Arizona in its ability to process "test-tube" reactions for human genetic analysis at a very high throughput, was able to deliver the genetics and computational expertise necessary to make this large-scale project competitive enough to secure NIH funding."

By discovering which genes are associated with CRSD, this study will lay the groundwork for better clinical diagnostics for this condition, as well as new therapies aimed at specific genes.

AHSC Fact: The Arizona Respiratory Center was designated the first Center of Excellence at the UA College of Medicine in 1971.

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