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Gene Mutation Helps Explain How Our Body Clock is Set

Published on September 19, 2014 in Cornerstone Blog · Last updated 4 months 1 week ago


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Most of us have failed to get enough sleep on a few occasions. Maybe it was as a college student studying for final exams, or as a new parent consoling an infant who is teething. Remember how you dragged through the next day in a bad mood and unable to focus?

Yet, a few people who are considered to be natural “short sleepers” seem to function well under the same sleep-deprived circumstances. Researchers at The Children’s Hospital of Philadelphia are investigating why some of us seem to need more sleep than others.

In a study published in the August issue of SLEEP, the study team described a new gene variant associated with short sleep and resistance to sleep deprivation in humans. Their findings support the hypothesis that genes related to circadian rhythms, in particular DEC2, can affect not only the timing of sleep, but also the magnitude of sleep homeostasis and sleep architecture.

Circadian rhythms control the biological clocks in our bodies. Homeostasis includes both short-term and long-term measures that the body uses to control and maintain an optimal internal environment.

“We found DEC2 is not only a circadian gene, but it is also related to homeostasis,” said Renata Pellegrino, PhD, senior research associate in the Center for Applied Genomics at The Children’s Hospital of Philadelphia, who collaborated on the study with an international study team. “That is why we are so excited. This gene could explain sleep length and how we respond to sleep deprivation, or why some of us sleep for a certain number of hours a night and others don’t.”

The researchers sequenced circadian clock genes in a cohort of healthy young adult twin pairs with no chronic conditions. Out of 200 twins, they identified a DEC2 mutation in one sibling who during baseline testing slept an average of five hours per night — more than an hour shorter than his twin brother who did not carry the gene.

The study team performed a series of cognitive performance tests to see how attentive each brother was after spending 38 hours without sleep in the sleep lab. The twin with the gene mutation performed better on psychomotor vigilance compared to his brother.

During unrestricted recovery sleep for one night following the 38 hours without sleep, the twins underwent electroencephalography that showed their brains’ electroactivity throughout the major sleep phases — Stages 1, 2, 3, 4 and REM. Stage 3 is characterized by Delta waves, which are high amplitude brain waves associated with deep, restful sleep. Stage 3 sleep also is related to maintaining homeostasis after sleep deprivation or wakefulness. The twin with the DEC2 mutation made more Delta waves and stayed in Stage 3 sleep longer than his brother.

The researchers went a step further to investigate how the DEC2 mutation interacted with other circadian clock genes. They discovered that the variant appears to alter the molecular mechanisms that set the duration of sleep that individuals need.

In the future, Dr. Pellegrino and her colleagues plan to form collaborations with researchers in other countries to see how common this variant is in other populations. They also would like to discover how the genes not only affect the brain, but also other body systems.

“True short sleepers in general are very resistant to sleep deprivation,” Dr. Pellegrino said. “They are very motivated and ready to go, so maybe the mutation protects you cognitively. But is there a price for that? We still don’t know the other metabolic effects.”

The study involved a collaboration among researchers from The Children’s Hospital of Philadelphia; the University of Pennsylvania School of Medicine; the Philadelphia Veterans Affairs Medical Center; Washington State University; Universidade Federal de Sao Paulo, Brazil; and Koc University, Istanbul, Turkey. The research was supported in part by grants from the National Heart, Lung, and Blood Institute, and the Institutional Development Fund from the Center for Applied Genomics at CHOP.