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Scientists Use New Tool to Track Activity of Autism-linked Genes

Study pinpoints when, where and how autism genes affect brain development; surprising commonalities may guide new therapies
November 21, 2013

A “Top Ten Advances in Autism Research 2013” Selection
See all the year’s “Top Ten” here.

In newly published research, investigators used new technology to track the activity of nine genes strongly linked to autism as these genes exerted their effects during brain development. To their surprise, the researchers found that all nine genes influenced the development of one type of brain cell in one brain region during one specific period of prenatal development.

The study may mark a turning point in how scientists make sense of the hundreds of autism-risk genes discovered in recent years, experts agree. The technique it used may also help pinpoint targets for future autism treatments. The report appears today in the journal Cell.

“This study helps explain how different genetic mutations can converge in time and space to influence a process that ultimately increases risk for autism,” comments Autism Speaks Chief Science Officer Rob Ring. 

Making sense of hundreds of autism-linked genes
In recent years, large-scale gene sequencing projects such as Autism Speaks 10K Genome Project have helped identify hundreds of genetic mutations associated with autism. Today’s report illustrates how scientists can use new technologies to decipher how these diverse gene changes influence brain development.

In their study, the investigators focused on nine genes strongly associated with autism. They investigated their effects using precise maps of gene expression during the development and aging of the human brain. (See graphic below.)

Specifically, they took advantage of BrainSpan, a digital atlas of brain development that maps how and where genes become active in the brain across the lifespan. This type of brain-activity mapping relies on donations of postmortem brain tissue to resources such as Autism BrainNet.

Many genes – one target
To their surprise, the researchers found that all nine genes contributed to abnormalities in one type of brain cell called cortical projection neurons. Moreover, the cell changes occurred in one small brain region – the deep layers of the prefrontal cortex. This brain region, at the front of the brain, is involved in complex decision making and social behavior.

What’s more, the researchers found that all the genes exerted their influence during the middle of prenatal development – three to five months after conception.

"Given the small subset of autism genes we studied, I had no expectation that we would see this degree of convergence," says senior author Matthew State, of the University of California-San Francisco. "This strongly suggests that though there are hundreds of autism risk genes, the number of underlying biological mechanisms will be far fewer.

“This is also a very important clue to advance precision medicine for autism toward the development of personalized and targeted therapies,” Dr. State adds.

Daniel Smith, Autism Speaks senior director of discovery research, comments: “This is a great example of why we do research on the genetic risk factors for autism. It illustrates a path from the identification of a genetic mutation associated with autism to a specific change in the brain that influences development and behavior. Uncovering the precise brain and body mechanisms that go awry during development will aid the discovery of more effective interventions.”

In a related study in the same issue of Cell, UCLA researchers describe mapping the activity of a great many other autism-risk genes in the brain. They, too, found that the genes' activities clustered around the development of particular brain cells or brain pathways during mid-prenatal development.