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

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

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