Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Splice variants reveal connections among autism genes

11.04.2014

A team of 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 has 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 in the April 11, 2014 online issue of 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.


Splicing variants (red) of autism genes were cloned from the brain and screened for interactions. The image on the right represents the network of interactions. Gray lines are interactions from a single isoform; red lines are interactions from additional isoforms of autism candidate genes (yellow circles).

Credit: UC San Diego School of Medicine

"When the newly discovered splice forms of autism genes were added to the network, the total number of interactions doubled," said principal investigator Lilia Iakoucheva, PhD, assistant professor 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 protein 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 protein variants produce such diverse patterns of interactions is exciting and quite unexpected."

The new network also illuminated how multiple autism genes connect to one another. The scientists 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. "This suggests that shared biological pathways may be disrupted in patients with different autism mutations," said co-first author Guan Ning Lin, PhD, a postdoctoral fellow in Iakoucheva's laboratory.

Beyond providing greater breadth and depth around autism proteins, the network represents a new resource for future autism studies, according to Iakoucheva. For example, she said the physical collection of more than 400 splicing variants of autism candidate genes could be used by other researchers interested in studying a specific protein variant. Some of the highly connected network partners may also represent potential drug targets. All interaction data will reside in the publicly available National Database of Autism Research.

"With this assembled autism 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 autism in 99.9 percent of cases remains unknown."

###

Co-lead authors of the study are Roser Corominas, Guan Ning Lin and Shuli Kang of the Department of Psychiatry, UCSD and Xinping Yang of the CCSB, Dana-Farber Cancer Institute. Other co-authors include Yun Shen, Lila Ghamsari, Martin Broly, Maria Rodriguez, Stanley Tam, Shelly A. Trigg, Changyu Fan, Song Yi, Michael A. Calderwood, Kourosh Salehi-Ashtiani, David E. Hill and Tong Hao, CCSB, Dana-Farber Cancer Institute; Murat Tasan and Frederick P. Roth, University of Toronto; Irma Lemmens and Jan Tavernier, Ghent University; Xingyan Kuang, Nan Zhao and Dmitry Korkin, University of Missouri; Dheeraj Malholtra, Jacob J. Michaelson and Jonathan Sebat, Beyster Center for Genomics of Psychiatric Diseases and UCSD Department of Psychiatry; Vladimir Vacic, New York Genome Center; and Steve Horvath, UCLA.

This research was funded, in part, by National Institutes of Health grants R01HD065288, R01MH091350, R01HG001715 and MH076431, the Ellison Foundation, the Dana-Farber Cancer Institute Strategic Initiative, the Simons Foundation Autism Research Initiative, a Canadian Institute for Advanced Research fellowship, the Canada Excellence Research Chairs Program and the National Science Foundation.

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

Further reports about: Autism Cancer Dana-Farber Psychiatry Splice discovered genes mutations patients proteins reveal variants

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>