UCSF researcher, Dr. Ying-Hui Fu, and her team have discovered the first gene involved in regulating the optimal length of human sleep.

“Short term and chronic disruptions in the length of optimal sleep can have serious consequences on cognition, mood and physical health, including cancer and endocrine function,” says Dr. Fu, UCSF professor of neurology.

Yu and her team identified a mutated gene in two members of an extended family that allowed the carriers to thrive on just six hours of sleep per day, versus the normal eight to eight-and-a-half hours that studies have shown to be optimal. The gene, known as hDEC2, is a transcription factor that represses expression of certain other genes and is implicated in the regulation of circadian rhythms. Working from this discovery, the scientists genetically engineered fruit flies and mice to express the mutated gene and study the impact.

The mice were fitted with EEG (electroencephalography) and EMG (electromyography) monitors to track their reduced nonREM and REM sleep, and the frequency of the fruit flies night-time movements were tracked using infrared light. As expected, the genetically modified participants slept less than the control organisms.

Additionally, the mutated mice were better able to compensate for the consequences sleep deprivation than the normal mice in the study.

“These changes in sleep homeostasis in the mutant mice could provide an explanation for why human subjects with the mutation are able to live unaffected by shorter amounts of sleep throughout their lives,” says Fu.

The next step, she says, is determining the DEC2’s precise role. “We know the gene encodes a protein that is a transcriptional repressor and we know it makes the repressor’s activity weaker. But we don’t know if the weaker repressor is directly related to the shorter amount of sleep, because proteins can have many functions. It could be the protein functions as part of a larger transcriptional machinery, not necessarily as a repressor.”

DEC2 could be involved in modulating “sleep quantity” alone, or it could be mediating both “sleep quantity” and “wakefulness-behavioral drive,” according to Fu. The latter drive, she says, is critical for the procurement of food, shelter, and mates and could be more potent in individuals with this mutation.

“The mouse model also provides an opportunity to investigate whether there are other behaviors or physiological conditions associated with a short sleep syndrome,” says Fu. She suspects there will be.

http://news.ucsf.edu/releases/first-human-gene-implicated-in-regulating-...