Discovering a genetic mutation is not a typical fantasy, but for Jesse Abelson, a former post-baccalaureate student at Yale, it was — and it recently became a reality that has led to advances in the study of Tourette’s Syndrome.
“It is the mutation that geneticists dream about,” Abelson said.
Yale researchers, led by Dr. Matthew State GRD ’01 of the Yale Child Study Center, published their results identifying a gene involved in Tourette’s Syndrome in the Oct. 14, 2005, issue of Science. This is the first time scientists have found a genetic mutation directly linked to Tourette’s.
“Tourette’s Syndrome is a disease that we have known for about 20 years has a genetic component, but it has been very hard to find those genes,” State said. “It’s what’s called a complex disorder, where multiple genes affect the disorder. We’ve had a very difficult time in identifying any specific gene.”
State, the senior author, said his lab has been pursuing research to identify genes involved in Tourette’s Syndrome for about eight years. Though the researchers discovered a gene involved in Tourette’s Syndrome, State said the lab did not find the only gene involved in Tourette’s.
Psychiatry professor Robert King, who is medical director of the Tourette’s clinic at the Child Study Center, said Tourette’s Syndrome is a misunderstood disease, often exaggerated by movies such as “Deuce Bigalow: Male Gigolo.”
“It’s characterized by motor and vocal tics, primarily in the early childhood,” King said. “The estimates are that as much as half a percent of kids may have it. Coprolalia [shouting out curses] is more the exception than the rule.”
King said Tourette’s cannot be narrowly classified.
“Both motor and vocal tics can be more complex … such as people having to repeat some phrases,” King said. “In a fair number of cases, it’s often associated with obsessions and compulsions. In kids, it’s often associated with ADHD.”
With these cases in mind, the scientists used genetic samples from patients with TS and tried to attach a genetic component to these traits.
Instead of first finding similarities in these, the researchers focused on identifying an individual with both TS and a chromosomal abnormality. This led them to probe the abnormal break point in the chromosome, where a section of the chromosome had been flip-flopped.
“Close by this spot were three genes, one of which looked like a good candidate for Tourette’s Syndrome,” State said.
Searching for the same gene in the genome of 174 other individuals with TS revealed three individuals with the same mutation. Given the vastness of the genome, State said, the corresponding mutations were significant, creating shock amongst the scientists. He said Abelson had to overcome much of his colleagues’ disbelief when he identified the frame-shift mutation.
“He stuck with his guns,” State said. “Sometimes scientific discovery is about when you identify something that doesn’t completely makes sense to you, you don’t pass on it. He just pursued it.”
The frame-shift mutation affected protein production and the binding of microRNA, a type of RNA that helps regulate protein production. Graduate student Kenneth Kwan played a crucial role in this discovery, State said.
Scientists remain uncertain of the ultimate impact of the research.
“In terms of how characteristic it is of the Tourette’s population as a whole, the jury is still out,” King said.
Still, State said, the research furthers the study of Tourette’s Syndrome.
“Even if this gene is responsible in only a small number of people,” he said, “the biology might be applicable to a large number of people by knowing what cells are involved.”