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Gene Regulates Sleep Length

Researchers have found a genetic mutation associated with waking up early. The discovery is a major step in understanding how the body controls sleep.

It's clear that our body needs sleep. Lack of sleep affects the way we think, behave, form memories and perform at work and school. People who get less sleep also have higher rates of obesity, heart disease, high blood pressure and diabetes.

The timing and duration of sleep varies between people. These tendencies run in families, suggesting they have a genetic basis. Although genes affecting sleep duration have been identified in some organisms, until now no similar human gene has been found.

A research team led by Dr. Ying-Hui Fu at the University of California at San Francisco sought out genes associated with short sleep duration in people. The scientists sequenced the DNA of candidate genes from families, searching for genetic links to extremely early wake up times. Their work was supported in part by NIH's National Heart, Lung and Blood Institute (NHLBI) and National Institute of Mental Health (NIMH).

In the August 14, 2009, issue of Science, they reported finding a mutation in a gene called hDEC2 in a family with 2 extremely early risers. A single DNA sequence change causes a switch from proline to arginine in the 385th amino acid of the DEC2 protein. Family members who carried this mutation slept an average of 6.25 hours, while noncarriers in the family averaged over 8 hours. The carriers naturally woke up earlier than noncarriers, even though they fell asleep at around the same time.

Mice have an equivalent gene, mDec2, that's known to be a component of the circadian clock, the system that coordinates our body's rhythms with periods of day and night. The researchers found that mice, as well as other mammals, normally have a proline at that position.

To confirm that the DEC2 mutation causes shorter sleep duration, the researchers created transgenic mice that carried hDEC2 genes instead of their own mDec2. Mice carrying the arginine version, they found, were awake about 8% longer during their light period (when mice usually sleep) than those carrying the proline version. The researchers saw a similar effect in fruit flies when they gave the flies the mutant gene.

These mice now provide a model for probing the effects of sleep on physical and mental health. This research could lead to a better understanding of why some people need to sleep longer than others. Eventually, it may yield insights into potential new therapies for sleep disorders.

—by Harrison Wein, Ph.D.