Shank3

A recent study sheds light on how a variety of different mutations in genes that seemingly have little in common can each result in the symptoms of autism. To answer this question, researchers developed a molecular map of protein networks or "interactome" to identify how proteins associated with ASD interact with hundreds of other proteins. Researchers used genes known to be associated with syndromic autism as a starting point for building the interactome. Syndromic autism occurs as part of a broader genetic disorder such as fragile X, Angelman syndrome, and Rett syndrome -- understanding protein interactions with syndromic autism may give insight into idiopathic autism, or autism with no known cause. Using 26 genes associated with syndromic autism, researchers hypothesized that the seemingly dissimilar genes might interact with shared partners in common molecular pathways, leading to the symptoms of autism. Indeed, researchers identified a complex network of 539 proteins that interacted with the autism-related proteins, successfully demonstrating that all of the proteins linked to autism are connected by interactions with common partners. The interactome confirmed previously suspected gene relationships and several new pairings, such as the connection between SHANK3 and TSC1, which share 21 common protein partners. Researchers then performed a microarray analysis on 288 individuals with idiopathic autism in a search for genes within the interactome. They identified three novel copy number variations -- chromosomal deletions and duplications -- on genes found in the network, demonstrating that the interactome may help to identify new genes related to ASD and understand complicated genetic variation.

--IACC 2011 Summary of Advances in ASD Research