Copy Number Variations

A recent collaborative study identified six genetic mutations that are strongly associated with autism spectrum disorder, including an area of DNA that likely holds clues to understanding the nature of human social behavior. The researchers estimate that these mutations represent only a few of the hundreds of spontaneously arising variants that are likely to increase autism risk. Using gene chip or microarray technology, the researchers analyzed the genomes of over 1,100 families with a single child on the autism spectrum, and compared the results of affected and unaffected siblings. The DNA samples analyzed in the study were part of the Simons Simplex Collection. The scan revealed a variety of copy number variants (CNVs) -- genetic mutations that can range from micro-deletions and duplications to large sequences of missing or additional DNA. Notably, one of the non-inherited or de novo CNVs was located on a genetic region linked to Williams-Beuren syndrome, a rare disorder that causes people to be extremely social, overly trusting, and highly empathetic.While loss of DNA from the area results in Williams-Beuren syndrome, gain of extra DNA in this area is associated with autism, which is marked by difficulty with social interaction and lack of empathy. This region's connection with both disorders suggests its importance in understanding the nature of the social brain. The study also supports earlier findings of higher rates of de novo CNVs in people with autism compared to their unaffected siblings. Uncovering the genetic basis of autism is critical to understanding the neurobiology underlying the disorder and may aid in developing targeted treatment approaches for different subtypes.

--IACC 2011 Summary of Advances in ASD Research

This research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling. While an association between genomic variants in certain nervous system processes and autism has been hypothesized in the past, this research definitively links these biological functions to autism. 

"This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both synaptic function and neurotransmission," said senior author Peter S. White, Ph.D., a molecular geneticist and director of the Center for Biomedical Informatics at The Children's Hospital of Philadelphia. Synapses are the contact points at which nerve cells communicate with other nerve cells, while neurotransmitters are the chemical messengers carrying those signals.

"Prior genomic studies of autism have successfully identified several genes that appear to confer risk for autism, but each gene appears to contribute to only a small percentage of cases," said the lead author, Xiaowu Gai, Ph.D. "Our approach considered whether groups of genes with common biological functions collectively accounted for a greater percentage of autism risk."

-- via Science Daily http://www.sciencedaily.com/releases/2011/03/110301111243.htm.