Researchers from the University of California, San Diego School of Medicine and the Center for Cancer Systems Biology (CCSB) at the Dana-Farber Cancer Institute have uncovered a new aspect of autism, revealing that proteins involved in autism interact with many more partners than previously known. These interactions had not been detected earlier because they involve alternatively spliced forms of autism genes found in the brain.
In their study, published online in Nature Communications, the scientists isolated hundreds of new variants of autism genes from the human brain, and then screened their protein products against thousands of other proteins to identify interacting partners. Proteins produced by alternatively-spliced autism genes and their many partners formed a biological network that produced an unprecedented view of how autism genes are connected.
“When the newly discovered splice forms of autism genes were added to the network, the total number of interactions doubled,” says principal investigator Lilia Iakoucheva, PhD. In some cases, the splice forms interacted with a completely different set of proteins. “What we see from this network is that different variants of the same protein could alter the wiring of the entire system,” Iakoucheva adds.
The new network illuminates how multiple autism genes connect to one another. Researchers found that one class of mutations involved in autism, known as copy number variants, involve genes that are closely connected to each other directly or indirectly through a common partner.
“We can begin to investigate how newly discovered mutations from patients may disrupt this assembled autism network,” says Iakoucheva. “This is an important task because the mechanism by which mutant proteins contribute to autism in 99.9% of cases remains unknown.” Read the article.Read more