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Ambitious Genetic Analysis of Schizophrenia Points to Early Brain Development

August 2, 2013. Rare mutations found in people with schizophrenia point the finger at genes involved in the early stages of building a brain, reports a study published August 1 in the journal Cell. By combing through the part of the genome that makes proteins, called the exome, Mary-Claire King of the University of Washington in Seattle and colleagues identified mutations in 54 different genes in subjects with schizophrenia. Further analysis indicated that these genes normally work together, particularly in the prenatal stages of brain development.

The findings support the long-standing notion that schizophrenia’s roots lie in early brain development. They also highlight the prefrontal cortex—a region important for complex mental processes—as vulnerable in the disorder.

The study is also noteworthy because it uses biological information to make sense of genetic results. So far, genetic findings in schizophrenia have implicated a diverse lot of genes, making it hard to pin the blame on any one gene. This means different people with schizophrenia could have the disorder for different genetic reasons. But King and colleagues looked to see if the 54 genes fingered in the new study have anything in common by gathering clues about where and when the genes are active in the brain and how they interact with other genes. Fifty of the 54 genes seemingly worked together early in development, with jobs such as making new brain cells, getting them into the correct position in the brain, and wiring them together. This means that the diverse set of genes implicated in schizophrenia may all play a role in disrupting early brain development. (For more details, see the related news story.)—Michele Solis.

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