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Autism Spectrum Disorders Health Center

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Research Probes Autism's Origins in the Brain

Two studies identify gene mutations that act together to disrupt the brain's wiring before birth


Focusing on the actions of these nine genes, the researchers checked the BrainSpan atlas to see if any were working together at the same time. They found that those genes and others associated with autism worked together at only three distinct places and periods in development. Those corresponded to the deeper layers of the front of the brain between 10 and 24 weeks after conception.

The gene mutations seem to interfere with the development of nerve cells that connect different brain regions.

"We know there's a disruption in the cells' development, but we don't know much more than that," Willsey said. "That's sort of the next step that our lab is addressing. That's what's going to help you progress toward treatment."

For the other study, researchers at the University of California, Los Angeles, took a different approach.

Using the BrainSpan data, they first looked at gene expression in normal brains from eight weeks after conception through 12 months of age. They then mapped hundreds of genes shared by individuals with autism and determined when and where those genes were active in the developing brain. Strikingly, although there were many autism risk genes, they all acted together at just a few points in brain development.

The researchers also compared the activity of autism risk genes to the genes involved in intellectual disability, or low I.Q. Although the conditions share many of the same risk genes, the study found that they were active in different ways at different times, adding more proof that the two conditions are distinct.

Their findings also pointed to a disruption in the brain's wiring, probably because of an error in the development of the brain-connecting nerve cells.

The researchers stressed, however, that the findings probably don't explain all cases of autism.

"These gene mutations definitely contribute to autism in some people," said Neelroop Parikshak, a graduate student at the University of California, Los Angeles, who led the second study. "[But] we don't know how much in a given individual."

Willsey agreed. He said that for the first time, however, these studies show the genetics of autism in action, something that should speed the path to better treatments.

"We feel this is a turning point," he said. "We're taking these genes and being able to tie them to a specific time point and a specific region in the brain, which really allows us to take the next step and follow this up in more detail. It's very exciting."

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