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Tuesday, October 26, 2021

Column: What makes Tourettes tic?

When neuroscientist Frank Sharp looks at a classroom of elementary-school students he sees the signs of Tourette Syndrome. Kids fidget, they squirm, they tic.

“One in 10 kids have tics in childhood,” Sharp said.

Most fidgety kids get over their tics. They stop drumming their hands on their desks or clicking their tongues.

My brother, John, had a tic that made him roll his eyes up whenever he blinked.

“It was stress related, I think,” John said.

My brother stopped his weird blinking thing around age 10.

But of those kids with tics, one in 100 develop Tourette Syndrome. People with Tourettes are plagued with involuntary verbal and physical tics. It’s a neurological disease that brings physical risks and public embarrassment.

Sharp, a professor of neurology, neuroscience and genetics at UC Davis, wants to stop Tourettes. He studies how the disease interacts with genetics and the immune system.

For Sharp, the science is personal.

Studying Tourettes was never Sharp’s plan. He graduated from UC Davis in 1968 with a degree in engineering. He went on to get his M.D., but he didn’t focus on Tourettes.

Then Sharp had a daughter. As she grew up, Sharp’s priorities changed – his daughter had tics that wouldn’t go away.

Tourettes is frightening for several reasons:

First, the disease is heritable, but it’s not dominant or recessive. Unlike genes for brown eyes or blue eyes, Tourettes will lie dormant for generations then pop up for no reason.

Second, though Tourettes runs in families, it’s invisible in a person’s DNA. Sharp said some people with Tourettes have genetic markers that predict the disease, but not all people with the markers get the disease. There are also plenty of people without genetic markers who still have Tourettes.

Sharp’s research into Tourettes is exciting because he’s looking into a new field called epigenetics. Epigenetics combines how the behavior of genes is affected by a person’s environment.

Epigenetics is tricky to understand. DNA is law. Right?

Nope.

A great example of epigenetics comes from the book Origins, by journalist Annie Murphy Paul. Paul describes a 2003 experiment at Duke University. Researchers took two groups of agouti mice – a strain of mice with a tendency to get diabetes and cancer. They fed one group of mice a regular diet, but the other group got a diet rich in certain nutrients.

At first, there was no change between the test group and the control. The researchers started seeing differences in the third generation of mice. Babies born to mice who had eaten the nutrient-rich diets throughout life were slender and less likely to get diabetes or cancer.

“Their DNA hadn’t changed – they still carried the agouti gene – but their epigenomes had,” writes Murphy Paul. “It was prenatal nutrition that had flipped the switch.”

Epigenetics is also important in cases of heart disease. Heart disease can run in families, but prenatal nutrition also affects health. Higher birth weight means reduced risk of heart disease.

Nature and nurture can work together.

After years of studying Tourettes, Sharp discovered a connection between Tourettes and the way genes copy themselves.

When cells split into new cells, their DNA has to be copied into identical strands. During this process, DNA is spliced into sections. In kids with Tourettes, the splicing step goes wrong. A section of DNA that should code for one protein is split, and the genes produce new proteins.

This splicing problem is heritable, which explains how Tourettes runs in families without actually showing up in genes.

No one’s sure how to stop the splicing errors, but epigenetics is encouraging. The solution could be something like prenatal nutrition, or it could be a lot more complicated. It’ll take a while, but Sharp sees epigenetics as an option for other diseases, like autism and multiple sclerosis.

“I thought the future for autism and Tourettes was dead,” Sharp said. “We have resurrected it.”

MADELINE McCURRY-SCHMIDT wants to answer your science questions in an upcoming column. Got a question about the world? E-mail Madeline at memschmidt@ucdavis.edu.

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