People tend to go to bed early and get up early people called “lark”, and the later the more mental people called “night owls”. Scientists have found that this difference in lifestyle habits is the result of a genetic mutation. Researchers at Rockefeller University found that a genetic variant, CRY1, slows down the body’s biological clock – the circadian clock – which normally determines when you feel sleepy each night and when you are ready to wake up. ready to wake up. People who carry this “night owl” mutation have a longer circadian cycle than most people, keeping them awake late into the night, the team reported April 6 in the journal Cell. Corresponding author Professor Michael W. Young, head of the Genetics Laboratory at Rockefeller University, noted, “This genetic variant has a greater impact than other sleep disorder-related mutations that are seen in only a few families.” This latest study shows that this mutation may be carried by one in 75 people in some populations. Diagnosing “night owls” Sleep disorders – from insomnia to narcolepsy – can make people vulnerable to chronic diseases, including diabetes, obesity and depression. People who self-classify as “night owls” are often diagnosed with delayed sleep phase syndrome (DSPD). Their 24-hour sleep-wake cycle is delayed, leaving them energized long after most people have slept. Sleeping late has its downside: Most people with DSPD are forced to wake up before their bodies tell them to in order to get to work or school on time, leading not only to insomnia in the first half of the night, but also to daytime fatigue. Letting the sleep cycle run free Young’s lab has been studying circadian biological clocks for more than three decades and has identified a number of genes that are associated with keeping flies, humans and other animals eating and sleeping on time. To find out if mutations in known circadian genes are associated with DSPD, Young and Alina Patke, assistant researcher, first author and co-corresponding author of the paper, collaborated with sleep researchers at Weill Cornell Medical College. Subjects were asked to spend two weeks in an experimental residence that was isolated from all information related to changes in circadian time, where they ate, drank and slept at their complete discretion. The researchers also collected skin cells from each individual. Most people follow a sleep-wake cycle of about 24 hours when they are in such a free environment. However, the researchers were intrigued by one DSPD subject who not only slept late, but whose cycle was about 30 minutes longer than others. In addition, the cycle of changes in body temperature and hormone levels that accompany the circadian biological clock – including melatonin, which helps regulate sleep – was also delayed. “In most people, melatonin levels start to rise at about 9 or 10 p.m.,” Young said. Young said, “In this DSPD patient, that didn’t happen until 2 a.m. or 3 a.m.” One patient points the way When the researchers tested the DNA of this DSPD patient, they found a variation: a mutation in CRY1, a gene known to be associated with the circadian cycle. In a healthy biological clock, a series of genes turn on and off in a 24-hour cycle. During some parts of this cycle, proteins encoded by CRY1 are generally responsible for repressing some of these genes. But Young and Patke found that the mutation found in this patient made the CRY1 protein more active than usual, causing other biological clock genes to stay off for longer. Image credit: The journal Cell The researchers further tested other members of the patient’s family and found that five relatives had this mutation in CRY1. They all also had manifestations of DSPD or had a history of persistent sleep problems. Young’s team then searched large genetic databases around the world to determine the prevalence of CRY1 mutations. Through Turkish collaborators, they identified for the first time many unrelated families and dozens of Turks carrying CRY1 mutations. After contacting these individuals and conducting interviews and questionnaires, the researchers confirmed that 38 people carrying the mutation had altered sleep behavior, while none of their relatives without the CRY1 mutation had abnormal sleep patterns. Finally, after screening for the CRY1 mutation in a large genetic database, Young’s team calculated that one in 75 people of non-Finnish European descent carried at least one copy of the DSPD mutation. This mutation is dominant, meaning that it only takes one copy to cause a sleep disorder. LiveScience reports that one of the study’s authors, Patke, is a “night owl” herself, but she tested herself and found no CRY1 mutation, so she thinks there may be other genetic factors. She believes there may be other genetic factors. The researchers said they are unsure of the benefits of testing for CRY1 mutations in people with DSPD. “Just finding the cause doesn’t immediately solve the problem.” Patke says, “but it’s not inconceivable that someone might develop a drug based on this mechanism in the future.” Right now, many people with DSPD are able to control their sleep cycles by following a strict schedule and going to bed before their bodies need them, Young says. “It’s kind of like quitting smoking, and there are things we can do to help with that before turning to medications.” He added that bright light exposure during the day seemed to help some patients. The team has planned future studies to explore whether the CRY1 mutation also affects the metabolic cycle in DSPD patients, since the human biological clock cycle is known to regulate not only sleep but also hunger as well as metabolite and hormone levels.