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New strategy could uncover genes at the root of psychiatric illnesses
Date:7/10/2014

Understanding the basis of psychiatric disorders has been extremely challenging because there are many genetic variants that may increase risk but are insufficient to cause disease. Now investigators reporting in the July 3rd issue of the Cell Press journal Cell Stem Cell describe a strategy that may help reveal how such "subthreshold" genetic risks interact with other risk factors or environmental exposures to affect the development of the nervous system. Their research pinpoints a genetic variant that may predispose individuals to schizophrenia.

The work takes advantage of a recently developed technology that allows skin cells from patients to be reprogrammed into induced pluripotent stem cells (iPSCs) that can then generate any cell type in the body. Through this technology, scientists obtained stem cells from individuals with a genetic abnormality that confers increased susceptibility to schizophrenia, and they observed deficits during nerve development that could be traced to a specific gene called CYFIP1, which helps maintain a nerve cell's structure. The team then blocked the expression of this gene in developing mouse embryos and noticed defects in the formation of the cerebral cortex, a brain region that plays an important role in consciousness.

Next, the scientists turned to human genetic studies to see how CYFIP might interact with other factors. They found that mutations in two genes within a cellular pathway linked to CYFIP1 led to a significantly increased risk of schizophrenia. The findings support the theory that multiple factors within the same pathway may interact to affect one's risk for psychiatric disorders.

"We were able to use a set of cutting-edge tools to gain insight into a critical cellular process for normal brain development, the dysregulation of which may be a manifestation of a genetic predisposition for schizophrenia," says senior author Dr. Guo-li Ming, of Johns Hopkins University School
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Contact: Mary Beth O'Leary
moleary@cell.com
617-397-2802
Cell Press
Source:Eurekalert  

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