Featured Research

from universities, journals, and other organizations

Gene linked to severity of autism's social dysfunction identified

Date:
April 7, 2011
Source:
Johns Hopkins Medical Institutions
Summary:
With the help of two sets of brothers with autism, scientists have identified a gene associated with autism that appears to be linked very specifically to the severity of social interaction deficits.

With the help of two sets of brothers with autism, Johns Hopkins scientists have identified a gene associated with autism that appears to be linked very specifically to the severity of social interaction deficits.

Related Articles


The gene, GRIP1 (glutamate receptor interacting protein 1), is a blueprint for a traffic-directing protein at synapses -- those specialized contact points between brain cells across which chemical signals flow.

Identified more than a decade ago by Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, and a Howard Hughes Medical Institute investigator, GRIP1 regulates how fast receptors travel to a cell's surface, where they are activated by a brain-signaling chemical called glutamate, allowing neurons to communicate with one another.

The new study, which tracked two versions of GRIP1 in the genomes of 480 people with autism, was published March 22 in the Proceedings of the National Academy of Sciences, and lends support to a prevailing theory that autism spectrum disorders (ASD), molecularly speaking, reflect an imbalance between inhibitory and excitatory signaling at synapses.

"The GRIP1 variants we studied are not sufficient to cause autism by themselves, but appear to be contributing factors that can modify the severity of the disease," says Tao Wang, M.D., Ph.D., assistant professor, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. "GRIP1 mutations seem to contribute to social interaction deficits in the patients we studied."

The Johns Hopkins researchers examined a part of the genomes of 480 patients with autism and compared these with 480 people of similar ethnicity without the disorder. They analyzed about 50 genes known to make proteins involved in a brain-signaling pathway, ultimately focusing their investigation on GRIP1, a protein found at both inhibitory and excitatory synapses, according to Wang.

Initially, looking under a microscope at normal mouse neurons and neurons with a mutant version of GRIP1, the investigators marked the receptor proteins with green fluorescence, added a chemical that promotes their "disappearance" deep inside a cell and timed the rates at which they disappeared -- leaving a cell unable to respond to signals from other cells. They also timed the reemergence of the protein back to the cell surface. With the GRIP1 mutant neurons, the receptors recycled to the surface twice as fast as in the normal neurons.

"If the receptors are recycling faster, the number of receptors on the surface is greater, so the cells are more sensitive to glutamate," Huganir explains. "The quicker the recycling, the more receptors on the surface and the stronger the excitatory transmission."

Even if just the excitatory synapses are affected, and the inhibitory ones don't change, that alone affects the relative balance of signaling, Huganir says.

Next, using 10 mice genetically engineered to lack both normal and mutant GRIP proteins, researchers watched what happened when each animal was put into a box where it could choose between spending time with a mouse it hadn't encountered before, or an inanimate object. They compared the behaviors of these mice with 10 normal mice put into the same social situation. Mice lacking both GRIP1 and GRIP2 spent twice as much time as wild-type (normal) mice interacting with other mice as they did with inanimate objects.

"These results support a role for GRIP1 in social behavior and implicate its variants in modulating autistic behavior," Wang says.

Finally, the team looked at the behavioral analyses of individuals in two families, each with two autistic brothers, and correlated their scores on standard diagnostic tests that assessed social interaction with their genotypes for GRIP1 variants.

In one family, the brother with two copies of the GRIP1 mutant variety scored lower on social interaction tests than his brother who had only one copy of the GRIP1 variant. The boys' mother, although not diagnosed as autistic, had a history of restricted interests, poor eye contact and repetitive behavior. Tests showed she also carried one copy of the variant.

In a second family, the autistic brother with one copy of the GRIP1 variant had lower social interaction scores than his autistic sibling without a GRIP1 variant.

Because the GRIP1 gene resides in synapses where other genes also implicated in autism have been found, this location is potentially important in terms of clinical relevance, says Huganir. The team plans to sequence hundreds more synaptic proteins in autistic patients to look for mutations and then follow up with functional analyses.

This study was supported in part by research grants from Autism Speaks Foundation and the National Institute of Child Health and Human Development. Authors on the paper from Johns Hopkins, in addition to Huganir and Wang, are Rebeca Mejias, Abby Adamczyk, Victor Anggono, Tejasvi Niranjan, Gareth M. Thomas, Kamal Sharma, M. Daniele Fallin, Walter E. Kaufmann, Mikhail Pletnikov and David Valle.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Journal Reference:

  1. R. Mejias, A. Adamczyk, V. Anggono, T. Niranjan, G. M. Thomas, K. Sharma, C. Skinner, C. E. Schwartz, R. E. Stevenson, M. D. Fallin, W. Kaufmann, M. Pletnikov, D. Valle, R. L. Huganir, T. Wang. Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism. Proceedings of the National Academy of Sciences, 2011; 108 (12): 4920 DOI: 10.1073/pnas.1102233108

Cite This Page:

Johns Hopkins Medical Institutions. "Gene linked to severity of autism's social dysfunction identified." ScienceDaily. ScienceDaily, 7 April 2011. <www.sciencedaily.com/releases/2011/04/110406123019.htm>.
Johns Hopkins Medical Institutions. (2011, April 7). Gene linked to severity of autism's social dysfunction identified. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2011/04/110406123019.htm
Johns Hopkins Medical Institutions. "Gene linked to severity of autism's social dysfunction identified." ScienceDaily. www.sciencedaily.com/releases/2011/04/110406123019.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
Yoga Could Be As Beneficial For The Heart As Walking, Biking

Yoga Could Be As Beneficial For The Heart As Walking, Biking

Newsy (Dec. 17, 2014) Yoga can help your weight, blood pressure, cholesterol and heart just as much as biking and walking does, a new study suggests. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins