New Autism Pathway undiscovered.

networkGround breaking collaborative from the University of California San Diego, San Diego of Medicine and the Dana-Farber has discovered a pathway that is connected with different forms of spliced that all contribute to the characteristics of .

The study published in the journal Nature communications, is the first to discover the gene communication network of alternatively spliced forms of in the brain. The proteins produced by the alternatively spliced and their metabolic partners form an biological network. The discovery of the new network also illustrates how how multiple connect to one another. The scientists found that one class of mutations involved in , known as copy number variants, involve that are closely connected to each other directly or indirectly through a common partner. The study may explain why there is such a wide difference in autistic spectrum disorders.

“When the newly discovered splice forms of were added to the network, the total number of interactions doubled,” said principal investigator Lilia Iakoucheva, PhD, in the Department of Psychiatry at UC San Diego. 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 could alter the wiring of the entire system,” Iakoucheva said.

“This is the first proteome-scale interaction network to incorporate alternative splice forms,” noted Marc Vidal, PhD, CCSB director and a co-investigator on the study. “The fact that variants produce such diverse patterns of interactions is exciting and quite unexpected.”

The network will be publicly available from the National Database of . “With this assembled network, we can begin to investigate how newly discovered mutations from patients may disrupt this network,” said Iakoucheva. “This is an important task because the mechanism by which mutant proteins contribute to in 99.9 percent of cases remains unknown.”

The network illustrates the lack of understanding contributing to diagnosis and treatment of and the potential for many to impact on the involved.


Roser Corominas, Xinping Yang, Guan Ning Lin, Shuli Kang, Yun Shen, Lila Ghamsari, Martin Broly, Maria Rodriguez, Stanley Tam, Shelly A. Trigg, Changyu Fan, , Murat Tasan, Irma Lemmens, Xingyan Kuang, Nan Zhao, Dheeraj Malhotra, Jacob J. Michaelson, Vladimir Vacic, Michael A. Calderwood, Frederick P. Roth, Jan Tavernier, Steve Horvath, Kourosh Salehi-Ashtiani, Dmitry Korkin, Jonathan Sebat, David E. Hill, Tong Hao, Marc Vidal, Lilia M. Iakoucheva. interaction network of alternatively spliced isoforms from brain links genetic factors for . Nature Communications, 2014; 5 DOI: 10.1038/ncomms4650

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