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Largest genomic search finds genes that may contribute to autism

An international team of researchers from 19 countries has identified one gene and a previously unidentified region of another chromosome as the location of another gene that may contribute to a child's chances of having autism.

The findings, based on genetic samples from nearly 1,200 families with two or more children who have autism, were published today in Nature Genetics by more than 120 scientists from Europe and North America who make up the Autism Genome Project.

The project was launched in 2002 by scientists at 50 institutions to share data, samples and expertise in an effort to speed up the process of identifying susceptibility genes, those that heighten a child's risk of having the developmental disorder. Seven University of Washington researchers are coauthors of the paper including lead project investigators Gerard Schellenberg and Geraldine Dawson.

The research was funded by Autism Speaks, a nonprofit organization dedicated to increasing awareness of autism and raising money to fund autism research, and the National Institutes of Health. The consortium scientists utilized statistical power from the largest set of autism-related genetic material yet examined. The researchers found neurexin 1, part of a family of genes that plays a role with the neurotransmitter glutamate, and a still-to-be-pinpointed gene on chromosome 11 to be likely susceptibility genes for autism.

"Neurexin 1 is a highly likely candidate," said Schellenberg, a researcher at the Puget Sound Veterans Affairs Medical Center and a research professor of medicine at the UW. "It is a protein that enables one neuron to contact another neuron. Often you don't have any idea of what a gene does, but in this case we know neurexin 1 is involved at sites where the neurotransmitter glutamate is released. Glutamate is a brain chemical that has been previously implicated in autism. The new finding suggests that the gene is potentially important in autism.

"As for the chromosome 11 location, we think there is another susceptibility gene there and we are actively pursuing it. We are in the neighborhood and have a plan to find it."

Dawson, who directs the UW's Autism Center and is a professor of psychology, said the identification of neurexin 1 is important because glutamate is known to be involved in learning. By identifying this gene it begins to allow researchers "to go from gene to brain to behavior in a way we haven't gone before," she said. "This is a pretty big step and is a precedent showing that autism will require this kind of collaboration to make progress. It is doubtful that any single laboratory could have come up with this kind of finding. This is just the beginning of the fruits from this collaboration."

The Autism Genome Project used two techniques to examine the DNA of the nearly 1,200 families with a history of autism. Researchers used so-called "gene chip" technologies to look for genetic similarities among these family members. In addition, the team scanned the same DNA for what are called copy number variations. These are submicroscopic insertions and deletions of genetic material that scientists believe may be involved with autism and other common diseases.

Schellenberg said copy number variations are fairly common in the human genome and many of them are believed to be benign. "But until you know the function, you don't know what happens when there is an insertion or deletion of this genetic material," he added.

Scientists believe that there may be five or six major genes and perhaps as many as 30 other genes involved in autism. Inheriting more of these genes or certain ones is thought to increase a child's likelihood of being born with autism or a more severe form of the disorder, just as there are genes that heighten a person's chances for inheriting breast cancer or heart disease.

Autism is actually a spectrum of disorders th at inhibits a person's ability to communicate and develop social relationships. It is often accompanied by extreme behavior challenges. Autism Spectrum Disorders are diagnosed in one of 166 children in the United States and affect four times as many boys as girls.

"These findings are a piece of the puzzle. As we identify these genes we will be able to screen young children for autism at an early age and begin interventions earlier, which can have a dramatic effect for some children," Dawson said.

A second phase of the Autism Genome Project also was announced today to continue the effort to discover the genes that cause the disorder. This $14.5 million phase is being funded by Autism Speaks, the British Medical Research Council, the Health Research Board of Ireland, Genome Canada and its partners, Canadian Institutes for Health Research, Southwest Autism Research and Resource Center, and the Hilibrand Foundation.


Source:University of Washington

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