Featured Research

from universities, journals, and other organizations

Misregulated genes may have big autism role

Date:
March 21, 2013
Source:
Brown University
Summary:
A genetic pathway involving proteins in the endosomes of cells appears to be misregulated in the brains of children with autism, according to a newly published statistical analysis. Previously, the genes were shown to cause rare forms of the disease, but the new study suggests they have a wider role.

Implicated in rare forms of autism, two genes may have wider role: Matthew Schewede, left, and Eric Morrow learned the value of studying rare forms of autism. Research is done not only for the patients who have rare conditions, but also because doing so can inform research about other forms of autism.
Credit: Image courtesy of Brown University

A new study finds that two genes individually associated with rare autism-related disorders are also jointly linked to more general forms of autism. The finding suggests a new genetic pathway to investigate in general autism research.

Related Articles


The genes encode the proteins NHE6 and NHE9, which are responsible for biochemical exchanges in the endosomes of cells. Mutations in the NHE6 gene are a direct cause of Christianson Syndrome, while mutations in the NHE9 gene lead to a severe form of autism with epilepsy. In the new study, a statistical analysis published in the journal Molecular Psychiatry, Brown University researchers and their colleagues found a specific pattern of misregulation of those two genes -- NHE9 is up-regulated and NHE6 is down-regulated -- in the brains of children with autism compared to the brains of non-autistic children.

"These genes play a role, not just in the rare forms of autism but also in the generalized pathology of autism," said Dr. Eric Morrow, professor of biology and professor of psychiatry and human behavior at Brown University, the paper's senior author. "In autism I think people get overwhelmed because there are hundreds of different genes. One of the important things is to find points of convergence where there are events that might be common across different forms."

The new study suggests that misregulation of NHE6 and NHE9 is one such event.

The research is based on a statistical analysis of messenger RNA samples from a bank of brain tissue donated posthumously by some children who had autism and some who did not. Messenger RNA is a key molecular player in the process of gene expression, making it an indicator of how gene expression was regulated in the cerebral cortex of each of the children.

Guided by Morrow, who studies autism genomics and sees autism patients at the E.P. Bradley Hospital in East Providence, lead author Matthew Schewede spent the summer of 2012 poring over the raw data, which was made available from a 2011 study led by co-author Daniel Geschwind and Irinia Voineagu of the University of California-Los Angeles.

Schwede, who studied statistics as an undergraduate at Harvard, is now a second-year student in the Warren Alpert Medical School. His classes are a block away from Morrow's lab, making the collaboration easy.

"We kind of stumbled on this," Schwede said. "At first we were just identifying what was up- and down-regulated in autism cerebral cortex in this data set."

But Schwede's findings about the NHE genes caught Morrow's attention in particular, because Morrow has been studying the NHE6 and NHE9 genes and the rare autism forms they cause.

"When we realized that some genes of interest for our lab were altered in the cerebral cortex, we focused the analysis on these genes in particular and how they were related to other processes," Schwede said.

Schwede made a second key finding: a strong and significant correlation between the misregulation of the NHE genes and the down-regulation of synapse genes, which is known to occur in autism.

Schwede's purely statistical analysis does not explain the physiology of how up-regulation of NHE9 and down-regulation NHE6 would affect synapse formation or general autism, but Morrow's biology group has a clear next step: to observe the neural and behavioral effects in the lab of misregulation of those genes in various experimental systems.

"That's a hypothesis that we can take to the mouse," Morrow said. "When we knock out these genes, how do the synapses change?"

The statistical results point out the value of studying rare forms of autism, not only for the sake the patients who have those conditions, Morrow said, but also because doing so can inform research about other forms of autism.

"We argue that it's relevant but sometimes, in fairness, we wonder about that," Morrow said. "A study like this really conveys strongly that that's a fair argument."

In addition Schwede, Morrow, and Geschwind, other authors are Krassimira Garbett and Karoly Mirnics of Vanderbilt University.

This grant was funded by the National Institute of Mental Health, the Simons Foundation for Autism Research Initiative, and the Nancy Lurie Marks Family Foundation. Schwede was funded by a summer research assistantship from the Alpert Medical School.


Story Source:

The above story is based on materials provided by Brown University. Note: Materials may be edited for content and length.


Journal Reference:

  1. M Schwede, K Garbett, K Mirnics, D H Geschwind, E M Morrow. Genes for endosomal NHE6 and NHE9 are misregulated in autism brains. Molecular Psychiatry, 2013; DOI: 10.1038/mp.2013.28

Cite This Page:

Brown University. "Misregulated genes may have big autism role." ScienceDaily. ScienceDaily, 21 March 2013. <www.sciencedaily.com/releases/2013/03/130321110931.htm>.
Brown University. (2013, March 21). Misregulated genes may have big autism role. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2013/03/130321110931.htm
Brown University. "Misregulated genes may have big autism role." ScienceDaily. www.sciencedaily.com/releases/2013/03/130321110931.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
You Don't Have To Be Alcohol Dependent To Need Treatment

You Don't Have To Be Alcohol Dependent To Need Treatment

Newsy (Nov. 21, 2014) A study by the Centers for Disease Control and Prevention found 9 out of 10 excessive drinkers in the country are not alcohol dependent. Video provided by Newsy
Powered by NewsLook.com
Your Complicated Job Might Keep Your Brain Young

Your Complicated Job Might Keep Your Brain Young

Newsy (Nov. 20, 2014) Researchers at the University of Edinburgh found the more complex your job is, the sharper your cognitive skills will likely be as you age. 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