Large study helps clarify the genetics of autism

Wednesday, June 9, 2010 — The findings, published online June 9 in the journal Nature, support an emerging consensus among scientists that autism is caused by many “rare variants” or genetic changes found in less than one percent of the population.

CHAPEL HILL — A large international consortium of researchers, including scientists at the University of North Carolina at Chapel Hill, have announced new discoveries that could help clarify the genetics of autism.

Their findings published online June 9th in the journal Nature, support an emerging consensus among scientists that autism is caused by many “rare variants” or genetic changes found in less than one percent of the population.

While each of these variants may only account for a small fraction of autism cases, collectively they appear to account for a greater percentage of individuals within the autism community. They are also providing into possible mechanisms involved in the disease.

The Autism Genome Project collected genotyping data from 1,000 individuals with autism spectrum disorder, or ASD, and 1,300 without ASD. They found that people with the disorder tend to carry submicroscopic insertions and deletions called copy number variants, or CNVs, in their genome. Some of these variants appear to be inherited, while others are considered new because they are found only in affected offspring and not their parents.

These CNV in individuals with ASD tend to disrupt genes previously reported to be associated with autism or intellectual disabilities.

The study also identified new genetic risk factors for autism (genes known scientifically as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus.) Some of these genes belong to nerve synapse-related pathways, while others are involved in cell proliferation, cellular movement, and intracellular signaling – functional targets that may lead to the development of new treatment approaches.

“These findings provide further evidence that autistic behavior is the result of many rare, small genetic changes,” said Joseph Piven, MD, study co-author and a lead AGP consortium investigator. Piven is also Sarah Graham Kenan Professor of Psychiatry at UNC and director of the Carolina Institute for Developmental Disabilities.

“While genetic abnormality or relevant CNV identified appears to account for only a handful of affected individuals, taken together these various CNVs in different locations throughout the genome are beginning to account for a significant number of occurrences of autism in the population. Identifying the genes and biological pathways associated with these genes will eventually lead us to new treatments for autism based an understanding of the underlying biological causes.”

Geraldine Dawson, PhD, research professor of psychiatry at UNC, also coauthored the new study.

The AGP consists of 120 scientists from more than 60 institutions representing 11 countries who formed this first-of-its-kind autism genetics consortium. Since 2002, the AGP researchers have shared their samples, data, and expertise to facilitate the identification of autism susceptibility genes. The first phase of the AGP, the assembly of the largest-ever autism DNA collection and whole genome linkage scan, was funded by the autism advocacy group Autism Speaks and the National Institutes of Health and completed in 2007.

The consortium is also co-funded by the Medical Research Council, Canadian Institutes of Health Research, Health Research Board (Ireland), Genome Canada and the Hilibrand Foundation.

Media contact: Thomas Hughes (919) 966-6047, tahughes@unch.unc.edu, or Les Lang (919) 966-9366, llang@med.unc.edu

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