Navigation Links
Study reveals how common gene mutation affects kids with autism spectrum disorders
Date:9/14/2012

Over the past decade, researchers have made great strides in identifying genes that lead to an increased risk of autism spectrum disorders (ASD), which result in a continuum of social deficits, communication difficulties and cognitive delays. But it's still critical to determine how exactly these genetic risk factors impact the brain's structure and function so that better treatments and interventions can be developed.

This led researchers at UCLA to look more closely at one particular culprit that's known to cause a susceptibility to ASD a genetic variant, or mutation, in the MET receptor tyrosine kinase gene, commonly known simply as MET.

And what they found was striking: For the first time, the researchers showed that the so-called "C" variant, which reduces MET protein expression, specifically impacts the network of connections among different areas of the brain involved in social behavior, including recognizing emotions shown on people's faces. While this gene variation is commonly found in the brains of both health individuals and those with ASD, the study showed that the gene has a bigger impact on brain connectivity in children with ASD.

The findings appear in the current online edition of the journal Neuron.

Senior author Mirella Dapretto, a professor of psychiatry at the Semel Institute of Neuroscience and Human Behavior at UCLA; first author Jeff Rudie, a graduate student in Dapretto's lab; and Pat Levitt, the Provost Professor of Neuroscience, Psychiatry, Psychology and Pharmacy at the University of Southern California, who discovered MET's association with ASD, used three different types of magnetic resonance imaging (MRI) to determine how the MET risk factor impacts brain structure and function.

Their findings provide new insight into understanding ASD heterogeneity the considerable individual differences in how ASD symptoms present which has challenged the field in developing more effective diagnostic tools and biologically based interventions for all affected children. Eventually, genetic information may be useful in identifying subgroups of individuals with ASD who may better respond to different types of treatment.

"Although researchers have begun to identify a variety of autism risk genes, the exact mechanisms by which genetic variation affects cellular pathways, brain networks and ultimately behavior is largely unknown," Rudie said. "We wanted to know how this risk allele may affect brain circuitry, predispose an individual to ASD and exacerbate these social deficits."

Other work has shown that the brains of individuals with autism have weak long-range connections yet possess excessive short-range connections when compared with healthy individuals. These connectivity problems could underlie the characteristic social problems of the disorder, said Rudie.

"Complex social behavior is known to rely on the rapid and dynamic integration of many different brain regions," he said.

"We wanted to know whether variations in the MET gene affected these connectivity patterns," Dapretto said.

The researchers used three magnetic resonance imaging methods functional MRI, resting-state functional MRI and diffusion tensor MRI to measure the structure and function of connections in the brains of 75 healthy children and 87 adolescents with ASD.

Across both groups, children and adolescents carrying the risk allele were found to display atypical activity in the brain as they observed a range of emotional faces (angry, fearful, happy, sad and neutral). This included hyperactivation of the amygdala, a structure in the brain that plays a key role in processing emotional information.

The researchers also found that the "C" variant disrupted both the functional and structural connectivity of brain networks involved in social behavior and which had been previously implicated in autism. The risk allele affected brain networks in both children who were developing typically and children with ASD but importantly, it was shown to have a stronger impact in individuals with ASD.

"What's interesting about this study is that we examined a mutation that's quite common in both healthy children and children with ASD," said Dapretto, who is also a member of UCLA's Center for Autism Research and Treatment. "We were able to show that a common mutation can play a significant role in neuropsychiatric disorders in a field where rare mutations, affecting a small proportion of individuals, have typically received the most attention."

In addition, she said, the findings have widespread implications for the field of neuroimaging, in that alterations in brain structure and function in clinical populations may in part reflect genetic vulnerability.

"Taken together, our findings break new ground in genebrainbehavior pathways underlying autism spectrum disorders and brain development more broadly," Rudie said.


'/>"/>
Contact: Mark Wheeler
mwheeler@mednet.ucla.edu
310-794-2265
University of California - Los Angeles
Source:Eurekalert

Related biology news :

1. Smart growth strategies curb car use, greenhouse gas emissions, SF State study suggests
2. UMD study shows exercise may protect against future emotional stress
3. Study of giant viruses shakes up tree of life
4. Study implicates marijuana use in pregnancy problems
5. University of Tennessee, ORNL lead national team to study nuclear fusion reactors
6. Study provides first-time analysis of 3 distinct contributions of forage fish worldwide
7. Mushroom-derived compound lengthens survival in dogs with cancer, Penn Vet study finds
8. Swim training plus healthy diet factor in cancer fight: New study
9. Turf study to monitor runoff, establish fertilizer management practices
10. UC Santa Cruz study shows how sea otters can reduce CO2 in the atmosphere
11. Study finds how BPA affects gene expression, anxiety; Soy mitigates effects
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/13/2016)... 2016  IMPOWER physicians supporting Medicaid patients in ... clinical standard in telehealth thanks to a new partnership ... platform, IMPOWER patients can routinely track key health measurements, ... index, and, when they opt in, share them with ... a local retail location at no cost. By leveraging ...
(Date:3/29/2016)... 2016 LegacyXChange, Inc. (OTC: ... SelectaDNA/CSI Protect are pleased to announce our successful effort ... variety of writing instruments, ensuring athletes signatures against counterfeiting ... from athletes on LegacyXChange will be assured of ongoing ... Bill Bollander , CEO states, "By ...
(Date:3/22/2016)... PROVO and SANDY, Utah ... Ontario (NSO), which operates the highest sample volume laboratory ... and Tute Genomics and UNIConnect, leaders in clinical sequencing ... announced the launch of a project to establish the ... panel. NSO has been contracted by ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016   Boston Biomedical , an ... designed to target cancer stemness pathways, announced that ... Orphan Drug Designation from the U.S. Food and ... cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin is ... inhibit cancer stemness pathways by targeting STAT3, and ...
(Date:6/23/2016)... , June 23, 2016 A person commits ... the crime scene to track the criminal down. ... U.S. Food and Drug Administration (FDA) uses DNA evidence to ... Sound far-fetched? It,s not. The FDA has ... to support investigations of foodborne illnesses. Put as simply as ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute approval ... of microbial tests introduced last year,” stated Bob Salter, Vice President of Regulatory ...
(Date:6/23/2016)... , June, 23, 2016  The Biodesign Challenge ... envision new ways to harness living systems and biotechnology, ... Art (MoMA) in New York City ... 130 participating students, showcased projects at MoMA,s Celeste Bartos ... Paola Antonelli , MoMA,s senior curator of architecture and ...
Breaking Biology Technology: