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Two Yale Teams among Science Top 10 for 2005

Yale Medicine Magazine, 2006 - Spring


Genetic mutations linked to brain development and disease were among last year’s leading discoveries.

Two findings by Yale scientists have been included in Science magazine’s list of the 10 leading scientific breakthroughs of 2005. The teams found evidence that both Tourette syndrome (TS) and dyslexia could stem from genetic defects linked to brain development. Their work was among research cited under the category “Miswiring the Brain.” Although the article did not name specific scientists or institutions, it cited “clues about the mechanisms of diverse disorders including schizophrenia, Tourette syndrome, and dyslexia. A common theme seems to be emerging: Many of the genes involved appear to play a role in brain development.”

Matthew W. State, M.D., Ph.D. ’01, the Harris Assistant Professor of Child Psychiatry and assistant professor of genetics, and the senior author of a report in the October 14 issue of Science, led the team that identified for the first time a genetic mutation associated with TS. The gene, which contributes to neuronal growth and communication, accounts for less than 2 percent of TS cases, but its discovery after years of searching offers the best chance yet to penetrate this socially debilitating disease. How the mutations participate with other genetic and environmental factors to increase risk for the disease is unknown. “We hope the clues this gene will give us will have widespread ramifications for understanding the basic biology of this disorder,” said State.

In its search for “that one unusual patient who would lead us to a gene,” State’s team found a child, diagnosed with TS and attention deficit hyperactivity disorder, who had a telltale break on chromosome 13. That clue led researchers to the nearby SLITRK1 (Slit and Trk-like family member 1) gene, which had already been recognized to be active in the developing brains of rodents and to function in neuron growth. When they analyzed the gene from 174 people with TS, they found three individuals with mutations. No mutations of any kind were found in several hundred unaffected people, providing strong evidence that SLITRK1 was contributing to the disease. Studying SLITRK1 gives a starting point, said State, who likened their discovery to a string the researchers can now pull on to start to unravel the rest of the disease.

Another team at the School of Medicine found a genetic link to dyslexia, the reading disorder that affects millions of children and adults. A mutated version of a gene, located on chromosome 6 and called DCDC2, disrupts the formation of brain circuits that make reading possible. The findings deepen the “understanding of how the reading process works on a molecular level,” said Jeffrey R. Gruen, M.D., HS ’84, FW ’88, associate professor of pediatrics and lead author of the study published in a special issue of Proceedings of the National Academy of Sciences in November.

In a study of DNA markers in 153 dyslexic families, Gruen’s team found that up to 20 percent of cases of dyslexia are due to defects in the DCDC2 gene. In the mutated version of the gene, a large regulatory region is deleted. Locating this gene explains, in part, why dyslexia occurs and could lead to early and more accurate diagnoses and more effective educational programs for dyslexic children.

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