Researcher discovers new regulatory autism gene

July 1, 2013

A new study by Valerie Hu, Ph.D., professor of biochemistry and molecular medicine at the George Washington University (GW) School of Medicine and Health Sciences (SMHS), reports that RORA, a novel candidate gene for autism discovered by her group in a 2010 study, regulates a large number of other genes associated with autism.

"We are focusing on this gene, in part, because this gene can act as a master regulator of other genes," said Hu, whose study was published in the journal Molecular Autism.

"Called nuclear hormone receptors, they are capable of activating or suppressing other genes in the genome. The question was which specific genes are regulated by RORA."

Hu and co-author, Tewarit Sarachana, Ph.D., a former doctoral student in the doctoral program at SMHS, found that RORA encodes a protein that can regulate the expression of more than 2,500 other genes. Of these 2,500 genes, many are known to be involved in and functions, and 426 of RORA's gene targets are already listed in AutismKB, a database of known autism .

To identify genes regulated by RORA, Hu and Sarachana used chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. This genome-wide ChIP-on-chip analysis of of RORA, as well as additional methods of validation, confirmed that RORA transcriptionally regulates the genes A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, such that when RORA levels are cut in half, all six genes also go down in their expression. The of these six genes are also reduced in RORA-deficient postmortem brain tissues from individuals with autism relative to that of age-matched unaffected controls.

"We see it as a , where RORA is a particularly shaky domino," said Hu. "If knocked over, it can also knock down a whole bunch of other genes, except that it's not just a single chain of events. There are multiple chains of events, leading to massive disruption of gene expression in autism."

A 2011 study by Hu's group revealed that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting that RORA may also contribute to the male bias of autism spectrum disorder.

Explore further: 18 novel subtype-dependent genetic variants for autism spectrum disorders revealed

More information: The new study, titled "Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder," is available online at

Related Stories

Scientists identify new gene linked to PTSD

August 7, 2012

Investigators at Boston University School of Medicine (BUSM) and Veterans Affairs (VA) Boston Healthcare System have identified a new gene linked to post-traumatic stress disorder (PTSD). The findings, published online in ...

Misregulated genes may have big autism role

March 21, 2013

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 ...

Researchers shed light on role of genes in autism

June 14, 2013

(Medical Xpress)—Research carried out by Medical Research Council (MRC) researchers at the University of Oxford has uncovered a chain of genetic events that are common in individuals with autism, and have examined for the ...

Recommended for you

New target could eliminate lurking cancer stem cells

November 27, 2015

Scientists from Trinity College Dublin have identified a novel target that could help to identify 'cancer stem cells' while they are in their inactive state. The scientists could then jolt these cells into action so that ...

New class of RNA tumor suppressors identified

November 23, 2015

A pair of RNA molecules originally thought to be no more than cellular housekeepers are deleted in over a quarter of common human cancers, according to researchers at the Stanford University School of Medicine. Breast cancer ...

Batten disease may benefit from gene therapy

November 11, 2015

In a study of dogs, scientists showed that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease, a rare and fatal neurological disorder. The key may be to inject viruses ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.