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New Gene Responsible for Average Sleep Duration Found

Sleep & Relaxation Sleep & Relaxation

The genetics of circadian rhythms have been well studied yet less is known about other types of genes that regulate how much sleep our bodies require.

One research team studied several members of a family who require significantly less sleep than average, functioning normally on only six hours of sleep. They identified a previously unknown gene that they believe has a direct impact on how much someone sleeps. The family whose DNA led to the identification of this gene is one of several being studied by the co-lead authors (Louis Ptáček, a neurologist and geneticist Ying-Hui Fu, both at the University of California, San Francisco). The gene, ADRB1, was identified using genetic linkage studies and whole-exome sequencing, which revealed a novel and very rare variant.

The first step in deciphering the role of the gene variant involved studying its protein in the test tube. “We wanted to determine if these mutations caused any functional alterations compared with the wild type,” Fu said. “We found that this gene codes for ß1-adrenergic receptor, and that the mutant version of the protein is much less stable, altering the receptor’s function. This suggested it was likely to have functional consequences in the brain.”

The researchers then conducted several experiments in mice carrying a mutated version of the gene. They found that these mice slept on average 55 minutes less than normal mice. (Humans with the gene sleep two hours less than average.) Further analysis showed that the gene was expressed at high levels in the dorsal pons, a part of the brain stem involved in subconscious activities such as respiration and eye movement as well as sleep.

Additionally, they discovered that normal ADRB1 neurons in this region were more active not only during wakefulness, but also during REM sleep. However, they were quiet during non-REM sleep. Furthermore, they found that the mutant neurons were more active than normal neurons, likely contributing to the short sleep behavior.

The researchers plan to study the function of the ADRB1 protein in other parts of the brain. They also are looking at other families for additional genes that are likely to be important. “Sleep is complicated,” Ptáček noted. “We don’t think there’s one gene or one region of the brain that’s telling our bodies to sleep or wake. This is only one of many parts.”

Fu adds that the work may eventually have applications for developing new types of drugs to control sleep and wakefulness. “Sleep is one of the most important things we do,” she said. “Not getting enough sleep is linked to an increase in the incidence of many conditions, including cancer, autoimmune disorders, cardiovascular disease and Alzheimer’s.”

Shi, et al. “A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors.” Neuron, 2019; DOI: 10.1016/j.neuron.2019.07.026.