Genetic Analysis Reveals Clues to Autism's Roots: Diverse Disorder Has Common Molecular Changes in Brain

By Sanders, Laura | Science News, June 18, 2011 | Go to article overview
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Genetic Analysis Reveals Clues to Autism's Roots: Diverse Disorder Has Common Molecular Changes in Brain


Sanders, Laura, Science News


Though autism and related conditions vary widely from person to person, shared brain changes may be at the root of these afflictions.

Changes in the behavior of genes important for brain-cell development and function contribute to the poorly understood disorders, a study published online May 25 in Nature shows. Figuring out what goes wrong in the multifaceted disease will help scientists design better ways to treat it.

"For us to be able to develop specific therapies that treat the cause, you have to understand the genetics," says pediatrician and autism researcher Hakon Hakonarson of the Children's Hospital of Philadelphia.

In the study, a team led by Daniel Geschwind of UCLA analyzed postmortem tissue from the brains of 19 people with autism spectrum disorder and 17 without. Patterns of gene activity differed in the two groups, as measured by levels of RNA molecules that shuttle information stored in DNA to the protein factories in cells. By sorting through these molecular patterns, the researchers turned up a number of abnormalities that the autistic brains shared.

For example, the researchers found that in unaffected samples hundreds of genes behaved differently depending on which of two very different areas were examined: one in the brain's frontal lobe, the other in the temporal lobe on the side of the brain. But in the autistic brains, only a handful of genes acted differently in the two areas, despite the fact that the regions are involved in completely different tasks. The frontal region manages planning, impulse control and other high-level reasoning tasks; among other things, the temporal region helps govern language and how a person relates to others.

This lack of distinction in gene activity may have behavioral consequences and probably emerges very early in a child's life, Geschwind says.

And though the affected brains differed from the unaffected brains, the autistic ones were surprisingly similar to one another, the team found. Among the 19 autistic samples, patterns of gene activity didn't vary much from person to person. Since the disease is thought to be caused by a mishmash of many different genetic and environmental factors, this was an unexpected result.

"It looks like there's a common pathology in autism, which is a surprising thing," Geschwind says. "In spite of having many different causes, there's some shared convergence."

In the study, the team pinpointed a number of genes that underperform in people with autism, showing lower levels of activity than in unaffected brains. Many of these genes are required for proper brain development and function, regulating how nerve cells find their correct partners and communicate.

Earlier studies by Hakonarson and others have found that people with autism are more likely to have particular versions of many of these same nerve cell-related genes. By showing those same genes don't just have slightly different DNA, but actually behave differently in the brains of people with autism, the new research confirms and extends those earlier results.

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