Nav: Home

Genetic changes that cause autism are more diverse than previously thought

March 24, 2016

The types of gene mutations that contribute to autism are more diverse than previously thought, report researchers at University of California, San Diego School of Medicine in the March 24 online issue of The American Journal of Human Genetics. The findings, they say, represent a significant advance in efforts to unravel the genetic basis of autism spectrum disorder (ASD).

To conduct their study, researchers enrolled hundreds of volunteers from families with one child affected by ASD and sequenced the complete genomes of every family member, including the parents and typically developing siblings. The researchers then looked for de novo mutations, gene alterations that appear spontaneously in one's offspring and are due to a mutation in a father's sperm or a mother's egg. Based on the authors' previous discoveries, it is known that de novo mutations contribute to risk, particularly in sporadic cases where there is no family history of autism.

The most common type of de novo mutations are spelling mistakes that change a single letter of the DNA code. However, in their new study, the researchers discovered many other mutations that introduce changes that are more complex. Called structural variants, these alterations involve the insertion or deletion of entire words or sentences of the DNA code.

The research team found a surprising variety of spontaneous mutations, from simple deletions or insertions to "jumping genes" - elements of DNA that copy and paste themselves into other parts of the genome. They also found that structural mutations sometimes occur in tight clusters where a combination of different mutations occur all at once.

"These mutations can insert, delete or in some cases scramble the DNA sequence," said senior author Jonathan Sebat, PhD, associate professor of psychiatry and cellular and molecular medicine and director of the Beyster Center for Genomics of Psychiatric Disease at UC San Diego School of Medicine.

Sebat and colleagues discovered that spontaneous structural mutations occurred at a surprisingly high rate in individuals - 20 percent -- and mutations in autism tended to disrupt genes. "Children with autism do not have more mutations overall," said Sebat, "but their mutations are more likely to disrupt genes involved in brain development."

The study, Sebat noted, highlights several genes that could play a key role in brain development. For example, the scientists identified a deletion in one gene called "stargazin" that is required for regulating the transmission of signals between neurons in the brain.

"Mutations in stargazin are very rare," said first author, William Brandler, PhD, a postdoctoral scholar in Sebat's lab, "but they point us to a biochemical pathway that may be important for social development. In the future, discoveries like this could lead to more effective personalized treatments for autism."
-end-
Funding for this research came, in part, from the National Institutes of Health (grants MH076431, HG007497, HD065288, MH104766 and MH105524), the Simons Foundation, the Autism Science Foundation and NIH predoctoral training grant T32-GM008666.

Co-authors include Danny Antaki, Madhusudan Gujral, Amina Noor, Gabriel Rosanio, Timothy R. Chapman, Daniel J. Barrera, Guan Ning Lin, Dheeraj Malhotra, Amanda C. Watts, Therese E. Gadomski, Oanh Hong, Karin V. Fuentes Fajardo, Abhishek Bhandari, Michael Baughn, Jeffrey Yuan, Terry Solomon, Alexandra G. Moyzis, Michelle S. Maile, Gail E. Reiner, Keith K. Vaux, Kang Zhang, Alysson R. Muotri, Karen Pierce, Eric Courchesne, Lilia M. Iakoucheva, UC San Diego; Lawrence C. Wong, Jasper A. Estabillo, Natacha Akshoomoff, Christina Corsello, Rady Children's Hospital-San Diego; Renius Owen and Charles M. Strom, Quest Diagnostics Nichols Institute; Stephan J. Sanders, UC San Francisco; and Suzanne M. Leal, Baylor College of Medicine.

University of California - San Diego

Related Autism Articles:

Genes, ozone, and autism
Exposure to ozone in the environment puts individuals with high levels of genetic variation at an even higher risk for developing autism than would be expected just by adding the two risk factors together, a new analysis shows.
A blood test for autism
An algorithm based on levels of metabolites found in a blood sample can accurately predict whether a child is on the autism spectrum of disorder (ASD), based upon a recent study.
New form of autism found
Autism spectrum disorders (ASD) affect around one percent of the world's population and are characterized by a range of difficulties in social interaction and communication.
Autism Speaks MSSNG study expands understanding of autism's complex genetics
A new study from Autism Speaks' MSSNG program expands understanding of autism's complex causes and may hold clues for the future development of targeted treatments.
Paths to Autism: One or Many?
A new report in Biological Psychiatry reports that brain alterations in infants at risk for autism may be widespread and affect multiple systems, in contrast to the widely held assumption of impairment specifically in social brain networks.
Raising a child with autism
Humans are resilient, even facing the toughest of life's challenges.
Explaining autism
Recognizing a need to better understand the biology that produces Autism Spectrum Disorder (ASD) symptoms, scientists at Duke-NUS Medical School (Duke-NUS) and the National Neuroscience Institute (NNI), Singapore, have teamed up and identified a novel mechanism that potentially links abnormal brain development to the cause of ASDs.
Autism breakthrough
Using a visual test that is known to prompt different reactions in autistic and normal brains, Harvard researchers have shown that those differences were associated with a breakdown in the signaling pathway used by GABA, one of the brain's chief inhibitory neurotransmitters.
New options for treating autism
The release of oxytocin leads to an increase in the production of anandamide, which causes mice to display a preference for interacting socially.
The Autism Science Foundation launches the Autism Sisters Project
The Autism Science Foundation, a not-for-profit organization dedicated to supporting and funding autism research, today announced the launch of the Autism Sisters Project, a new initiative that will give unaffected sisters of individuals with autism the opportunity to take an active role in accelerating research into the 'Female Protective Effect.'

Related Autism Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...