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Discoveries Shed Light on Autism & Psychiatric Disorders

Researchers have used a new approach to identify 33 genes that affect the development of autism and related disorders. Their research suggests that certain changes in these genes predispose to the development of autism, while different changes predispose to psychiatric disorders such as schizophrenia.

“This is a first step in what will be a long journey toward understanding genes underlying the pathophysiology of neurodevelopmental and psychiatric disorders and developing new clinical treatments," says senior author James Gusella, Ph.D., director of the Massachusetts General Hospital Center for Human Genetic Research and a professor of neurogenetics at Harvard Medical School.

The study, appearing online today in the journal Cell, was supported in part by a grant from Autism Speaks, as well as grants from the National Institutes of Health and the Simons Foundation. It involved researchers from 15 institutions in three countries, including Harvard Medical School, Massachusetts General Hospital, the Broad Institute and Brigham and Women's Hospital.

By sequencing the genomes of individuals with abnormal chromosomes and neurodevelopmental abnormalities, the researchers identified the precise points where each gene’s DNA was altered. “As a result, we were able to discover a series of genes that have a strong individual impact on these disorders,” Gusella says. “We also found that many of these genes play a role in diverse clinical situations – from severe intellectual disability to adult-onset schizophrenia – leading to the conclusion that these genes are very sensitive to even subtle perturbations.”

Gusella and his team looked at gene changes known as balanced chromosome abnormalities (BCAs). These involve the movement of entire DNA segments either within the same chromosome or in exchange with segments in other chromosomes with minimal loss or gain of genetic materials. As a result they leave the overall size of the chromosomes unchanged. Several years ago Gusella and colleagues identified developmentally important genes by investigating BCAs. More difficult was the task of identifying where BCAs “break” and disrupt genes.

To get a clearer view of the potential impact of BCAs on autism, the research team took advantage of a new approach developed by Michael Talkowski, Ph.D., the lead author of the Cell paper. It allows sequencing the genome in a way that detects BCA breakpoints. The whole procedure can be accomplished in less than two weeks rather than the many months previously required for full-genome sequencing.

In this study, it associated autism and related disorder with 33 disrupted genes, only 11 of which had been previously linked to autism.

As they compiled their results, the researchers were struck by how many of the BCA-disrupted autism genes had been previously associated with psychiatric disorders. Their findings suggest that, though many of the same genes were involved in the development of different conditions, they were altered in different ways when associated with psychiatric disorders versus neurodevelopmental disorders such as autism.  

“This research underscores the complexity of genetic contribution to these conditions,” says Andy Shih, Ph.D., Autism Speaks vice president for scientific affairs. “They also underscore how at the molecular level, autism and other neurodevelopmental disorders may have commonalities with psychiatric conditions such as schizophrenia, whose symptoms emerge in adolescence and early adulthood. Genetic findings such as these are vital for deepening our understanding of autism, with important implications for how we think about and pursue the development of new treatments and possible prevention.”

Thanks to the support of its families, donors, volunteers and other supporters, Autism Speaks funds a wealth of research advancing the scientific understanding, treatment, and prevention of autism spectrum disorders. You can explore this research using this website’s Grant Search