UMMS researchers identify epigenetic signatures of autism

November 07, 2011

WORCESTER, Mass. - Scientists at the University of Massachusetts Medical School are the first to map epigenetic changes in neurons from the brains of individuals with autism, providing empirical evidence that epigenetic alterations--changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence--may play an important role in the disease.

Analysis of these variations revealed hundreds of genetic sites that overlap with many of the genetic regions known to confer risk for Autism Spectrum Disorders. The study was published in Online First by the Archives of General Psychiatry.

Autism spectrum disorders are a group of complex biological illnesses with a variety of origins. People with a disorder on the autism spectrum often struggle with social interactions and communication. Many suffer from delayed language skills, as well as restricted interests and repetitive behavior. It's estimated that only 10 percent of cases are a result of genetic mutations. The cause of the remaining 90 percent of cases is unknown.

"We know that autism is a biological disorder," said Schahram Akbarian, MD, PhD, director of the Irving S. and Betty Brudnick Neuropsychiatric Research Institute and professor of psychiatry at the University of Massachusetts Medical School. "But very little is known about the genetic and molecular underpinnings associated with the disorder. It's been hypothesized that an epigenetic model of autism could potentially explain why genetic screening strategies for the disorder have been so difficult and frustrating. Our study is the first clear evidence gained exclusively from nerve cells pointing to a link between epigenetic changes and known genetic risk sites for autism."

In order to see if epigenetic changes were occurring in individuals with autism, Akbarian and colleagues developed a novel method for extracting chromatin - the packaging material that compresses DNA into a smaller volume so it can fit inside a cell's nucleus - from the nuclei of postmortem nerve cells. Using tissue samples obtained through the Autism Tissue Program from 16 individuals diagnosed with an autism spectrum disorder, Akbarian and colleagues used deep sequencing technology to compare these tissue samples with 16 control samples for changes in histone methylation, a small protein that attaches to DNA and controls gene expression and activity.

After analyzing the sequenced DNA data, Zhiping Weng, PhD, director of the Program in Bioinformatics and Integrative Biology and professor of biochemistry & molecular pharmacology at UMass Medical School, found hundreds of sites along the genome affected by an alteration in histone methylation in the brain tissue from the autistic individuals. However, less than 10 percent of the affected genes they observed were the result of a mutation to the DNA sequence.

"Neurons from subjects with autism show changes in chromatin structures at hundreds of loci genome-wide, revealing considerable overlap between genetic and epigenetic risk maps of developmental brain disorders," said Akbarian.

"Our understanding of psychiatric disorders, such as autism, is burdened by the fact that we often can't see the structural changes that lead to disease," said Akbarian. "It's only by studying these diseases on the molecular level that scientists can begin to get a handle on how they work and understand how to treat them."
-end-
About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $307 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of the Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. For more information, visit www.umassmed.edu.

University of Massachusetts Medical School

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.