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: Scientists identify new gene linked to PTSD

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 www.molecularautism.com/content/4/1/14

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 ...

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 ...

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 ...

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

April 27, 2011
By dividing individuals with autism spectrum disorders (ASD) into four subtypes according to similarity of symptoms and reanalyzing existing genome-wide genetic data on these individuals vs. controls, researchers at the George ...

Recommended for you

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

0 comments

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.