Missing gene leads to missing sleep


Williams with a tray full of her research subjects.

Photo by Daniel R. Burke

Having trouble falling asleep? The problem may lie in your genes.

At least that’s what recent research on fruit flies indicates.

A group of researchers headed by Julie Williams, Howard Hughes Medical Institute research associate in Penn’s Department of Neurobiology, have discovered that a gene known as Nf1 is responsible for maintaining circadian rhythm — sending the signals the body’s master clock uses to govern rest and activity.

Researchers had already known that the Nf1 gene plays an important role in regulating the growth of tumors. The gene takes its name from the fact that without it, humans develop a condition known as neurofibromatosis, in which tumors grow unchecked, often leading to cancer before adulthood.

Williams’ team established that in the Drosophila fruit fly, the Nf1 gene is required to send signals from the flies’ circadian clock along the protein pathway that leads to other body parts, and that the pathway used in the fruit fly is the same as the one the gene uses in humans.

But, she noted, “People who had worked on Nf1 in mammals were dismissive of our work with fruit flies.” They thought that the phenomena the fruit-fly researchers identified were different from what happened in mammals. As it turns out, the phenomena are quite similar. In fruit flies as in mammals, the absence of Nf1 leads to size abnormalities, learning disabilities and sleep disorders.

As team members presented their findings at conferences, the feedback they got gave anecdotal support to that parallel. “We heard a lot of anecdotal reports from physicians that their patients reported some kind of sleep disturbance,” she said. “And when I presented the same paper, a San Francisco neurologist said that he uses sleep [disorders] as a diagnostic for [neurofibromatosis].”

The Penn research confirms this anecdotal evidence. “We found that [the fruit flies’] clocks were functioning normally, but without Nf1, the clock could not send signals,” Williams said.

The results further demonstrate the usefulness of Drosophila as a research subject for human ailments. “Fruit flies are extremely useful for studying human disease,” Williams said. “They’re simpler, their lifespan and reproductive cycle is shorter, and the tools we have to manipulate their genes are more sophisticated than the ones we have for mammals.

“You can do similar things in mice, but it takes longer and it’s harder to do.”

It also suggests that further study of the phenomenon in mammals is warranted. “The next step is that clinicians should look at this in humans.”

Williams does not see this research as leading to a genetic treatment for sleep disorders in the near term.

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Originally published on October 11, 2001