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:5/20/2016)... 20, 2016  VoiceIt is excited to announce ... By working together, VoiceIt and VoicePass ... and VoicePass take slightly different approaches to voice ... security and usability. ... new partnership. "This marketing and technology ...
(Date:5/3/2016)... May 3, 2016  Neurotechnology, a provider of ... MegaMatcher Automated Biometric Identification System (ABIS) , a ... projects. MegaMatcher ABIS can process multiple complex biometric ... combination of fingerprint, face or iris biometrics. It ... and MegaMatcher Accelerator , which have ...
(Date:4/26/2016)... , April 27, 2016 ... the  "Global Multi-modal Biometrics Market 2016-2020"  report to ... ) , The analysts forecast the ... CAGR of 15.49% during the period 2016-2020.  ... number of sectors such as the healthcare, BFSI, ...
Breaking Biology News(10 mins):
(Date:5/18/2016)... ... May 18, 2016 , ... Shimadzu Scientific ... The University of Toledo. This two-day camp will take place annually starting June ... field of pharmaceutical sciences in preparation for a university academic program. , ...
(Date:5/18/2016)... ... 18, 2016 , ... Every day, more than 5,400 ER ... Costing more than $56 billion in direct costs annually, asthma remains a critical ... the suffering associated with uncontrolled asthma can be overwhelmingly disproportionate and better managed,” ...
(Date:5/17/2016)... May 18, 2016 Haselmeier announces ... pen following approval by EMA, the European Medicines Agency. ... and technology company, the new pen version includes enhancements ... level of confidence to patients during use. ... pen easier to handle with a larger display window ...
(Date:5/17/2016)... ... 2016 , ... PATH and Laerdal Global Health announced today ... feeding cup to market based on a reference design co-developed by PATH, the ... Hospital, thereby ensuring an innovative feeding option for the 7.6 million preterm infants ...
Breaking Biology Technology: