A mutant gene behind an "early bird" sleep disorder has been identified by American researchers. Approximately three-tenths of a percent of the world's population has familial advanced sleep phase syndrome (FASPS), according to the researchers. People with this "time-shift" trait have body clocks that are out of sync with most of the world. Researchers say they have found the genetic culprit for this rare sleep disorder.
People with this sleep disorder do not suffer from sleep deprivation. Rather, they consistently fall asleep at an early hour and then wake up well before dawn.
Often those with FASPS adjust their schedules to this. In fact, many people with this sleep disorder are proud that they can use the time to get things done without daylight distractions. However, others are bothered by such a time-shift. The problem can be serious enough to reduce their ability to keep a job or function normally in society.
Researchers at the University of California at San Francisco and Howard Hughes Medical Institute discovered that the mutation responsible for FASPS lies in a mutant gene, CKIdelta. The sleep-shifting mutation they found is in "a gene that was not previously shown in mammals to be a circadian rhythm gene," said HHMI neurologist Dr. Louis Ptacek in a UCSF news release.
This gene which controls the production of a protein is now believed to play an important role in regulating circadian rhythm. The researchers studied three generations of a family in which five people were affected by FASPS. DNA samples showed that those with abnormal sleeping patterns shared a particular sequence in a gene that the others did not.
They made the discovery by taking blood samples of the individuals and then using linkage analysis to hone in on the region of DNA within the chromosomes most likely to reveal the relevant gene, based on what was known about other genetic markers related to circadian rhythms. The gene was found on chromosome 17. The mutated form was compared to the gene in family members who did not have FASPS.
Researchers found that those with FASPS also suffered from migraines and asthma. This finding suggests that these symptoms may be part of the same syndrome.
Researchers have not found the direct mechanism by which this CKIdelta affects a person's sleep cycle. The mutant gene behaves differently in different species. The gene was tested in human mice and fruit flies.
"These results show that the gene is a central component of the mammalian circadian clock," the researchers wrote in the science journal Nature. Ptacek said, "The discovery of the gene opens the window just a crack, but it could let in a lot of light for probing the neurobiology of the brain. It is possible that insights into how the human clock works will allow treatment of other circadian problems like jet lag or shift work."
Dr. Ying-hui Fu, lead author of the paper in Nature, said in the news release: "Evidence suggests that circadian rhythms may have a fundamental role in numerous behaviors. As the enzyme produced by the gene modulates many proteins, we may test for its impact on learning and memory too."
The researchers also suggest that the mammalian and fly clock may have different regulatory mechanisms. They believe that further studies will demonstrate how this mutant gene works in different settings and genetic backgrounds.
Ultimately, Fu said she and her colleagues hope their research will lead to a better understanding of how the human clock ticks and controls behavior. Such knowledge may lead to therapeutic treatments for everything from sleep disorders to potentially related ailments such as depression and cancer.
