Navigation Links
Misregulated genes may have big autism role
Date:3/21/2013

PROVIDENCE, R.I. [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.

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 online this week 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 CaliforniaLos 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."


'/>"/>

Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

Related medicine news :

1. Virus and genes involved in causation of schizophrenia
2. Studies advance knowledge of HIV impact on hepatitis C infection and genes that may thwart HCV
3. Researchers show that lipid nanoparticles are ideal for delivering genes and drugs
4. Shared Genes May Link ADHD, Autism and Depression
5. For some, surgical site infections are in the genes
6. Sleep Deprivation May Disrupt Your Genes
7. Researchers identify variations in 4 genes associated with an increased risk of colorectal cancer
8. Researchers identify variations in four genes associated with an increased risk of colorectal cancer
9. Scientists Find 24 New Genes Linked to Nearsightedness
10. Many Cocaine Deaths Determined by Genes, Study Says
11. Epigenetic control of cardiogenesis
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Misregulated genes may have big autism role
(Date:8/18/2017)... ... August 18, 2017 , ... ... LLC (“Quick”), a highly specialized asset-light logistics provider of complex transport solutions ... definitive agreement to purchase Unitrans International Corporation, a division of Roadrunner Transportation ...
(Date:8/18/2017)... (PRWEB) , ... August 18, 2017 , ... ... this summer’s edition of “Vision & Hearing,” advocating for active, healthy lifestyles and ... on resources available for individuals with hearing impairments and shares the latest innovations ...
(Date:8/18/2017)... , ... August 18, 2017 , ... ... handling handheld devices. Through an educational webinar, they will present the line of ... chance to learn how easy you can automate everyday pipetting tasks. , Ideal ...
(Date:8/18/2017)... ... August 18, 2017 , ... Hernandez Insurance Agencies, a northern ... the greater DC region, is inaugurating a “New Leash On Life” charity initiative ... training them to be companions for veterans in need. , The Semper K9 ...
(Date:8/18/2017)... ... 18, 2017 , ... Moore Insurance, a Houston area agency ... is launching a regional charity effort to provide publicity assistance and generate donations ... Tumor Foundation (PBTF) has raised nearly $30 million in donations that has been ...
Breaking Medicine News(10 mins):
(Date:7/28/2017)... 2017 Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), ... ended June 30, 2017, and updated its financial outlook ... For the fiscal third quarter, Hill-Rom reported earnings ... diluted share in the prior-year period. These results reflect ... diluted share primarily related to the non-cash write-down of ...
(Date:7/27/2017)... July 27, 2017  West Pharmaceutical Services, Inc. (NYSE: ... for the second-quarter 2017 and updated financial guidance for ... Second-Quarter 2017 Highlights Reported net sales ... the prior-year quarter. Net sales at constant currency (organic) ... EPS was $0.51, compared to $0.60 in the prior-year ...
(Date:7/26/2017)... , July 26, 2017 Sancilio Pharmaceuticals Company, ... our clinical trial evaluating Altemia TM , an oral ... and Sickle Cell Disease (SCD). The SCOT Trial, is ... efficacy and safety of Altemia TM in pediatric ... under US IND 125274. ...
Breaking Medicine Technology: