Health Science Reviews

by May Krause

Do you consider yourself a night owl? Do you struggle to fall asleep and wake up early in the morning, hitting the snooze button a few too many times? This may be the cause of a genetic mutation, meaning we now have a medical excuse for missing that 8 am lecture.

Researchers from The Rockefeller University discovered a genetic mutation, altering the timing of the biological clock. The result of this is a common sleep syndrome called delayed sleep phase disorder (DSPD) or “Night Owl Syndrome”.  It is estimated that a whopping 15% of people in the United States struggle with this disorder.

Normally the intrinsic circadian clock promotes 24-hour rhythms, that are essential for daily human activity and body functioning. The 24-hour cycle consists of a negative feedback loop where transcription factors, Clock and Bmal1, produce inhibitors (of the Per and Cry family). These inhibitors gradually repress the transcription factors which are eventually silenced and therefore no longer produce inhibitors. Once all the inhibitors have degraded, the transcription factors regain their maximum potency, thus starting the cycle all over again.

The researchers sequenced the genes that form the mammalian circadian clock from the DNA of a patient thought to have DSPD. A mutation in the CRY1 gene was found, a gene already implicated in the circadian cycle. This gene mutation results in an altered protein expressed leading to the inhibitor being hyperactive. A hyperactive inhibitor causes the activators to be repressed for too long, extending the circadian cycle by at least half an hour.

To test whether the circadian abnormalities in this individual were related to the observed modification of CRY1, information on sleep patterns was obtained from the proband’s family members. The individuals were genotyped for the presence or absence of the candidate allele. Delayed sleep behaviour was found to be common among family members of both sexes and across several generations. This led the researchers to conclude an autosomal-dominant inheritance pattern.

So besides being an easy excuse as to why you overslept, this discovery may lead to the development of drugs in the future based on this mechanism that has been uncovered. Perhaps a drug that would reduce the activity of the hyperactive CRY1 protein in individuals with this disorder. Additionally, I believe that more research should be done around this since the human circadian cycle is known to not only regulate sleep but also hunger and levels of metabolites and hormones. How does the CRY1 mutation in people with DSPD affect this? Hopefully, the answer to this becomes clear soon, but until then I’ll carry on hitting my snooze button a few too many times. 

Reference

Patke, A., Murphy, P. J., Onat, O. E., Krieger, A. C., Özçelik, T., Campbell, S. S., & Young, M. W. (2017). Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder. Cell, 169(2), 203-215.e13. https://doi.org/10.1016/J.CELL.2017.03.027