World's largest DNA scan for autism uncovers new gene variant for disorder

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World's largest DNA scan for autism uncovers new gene variant for disorder

Apr 28 2009, 2:35 PM EST

EUREKALERT

Contact: Roxanne Moster

rmoster@...

University of California - Los Angeles

Gene most active in brain regions critical to language, social behavior

UCLA scientists, in partnership with 30 research institutions across the

country, have identified a new gene variant that is highly common in autistic

children. And when researchers scrutinized the activity of the gene, known as

CDH10, in the fetal brain, they discovered that it is most active in key regions

that support language, speech and interpreting social behavior.

Published April 28 in the advance online edition of the journal Nature, the two

findings suggest that CDH10 plays a critical role in shaping the developing

brain and may contribute to a prenatal risk of autism.

A variant is a gene that has undergone subtle changes from the normal DNA yet is

shared by a significant portion of the population.

" While this gene variant is common in the general population, we discovered that

it occurs about 20 percent more often in children with autism, " said study

author Dr. Geschwind, director of the UCLA Center for Autism Treatment

and Research. " A major change like this in the genetic code is too common to be

a simple mutation it is a risk factor in the origin of the disease. "

Using the largest population sample to date, the scientists systematically

scanned the DNA of 3,100 individuals from 780 families nationwide. Each family

had at least two autistic children.

The scan connected autism to a specific region of chromosome 5, which previous

studies at UCLA and collaborating institutions had pinpointed as a hub for

genetic variations linked to higher autism risk.

To verify the findings, Dr. Hakon Hakonarson at the Children's Hospital of

Pennsylvania led the team in conducting a second scan on the DNA of 1,200

individuals from families affected by autism, as well as nearly 6,500 healthy

controls. All participants shared European ancestry.

The scientists evaluated the relationship of more than half a million gene

variants to autism and consistently discovered six changes that occurred more

frequently in autistic children than in the control group. These variants sat on

chromosome 5 between two genes, CDH9 and CDH10.

In the second half of the study, the UCLA team looked at the two genes' presence

in the developing human brain. While CDH9's presence appeared minimal, the

scientists discovered that CDH10 was most active in the fetal brain's frontal

cortex, a region critical to language, social behavior and complex thought

processes such as judgment.

" This is a landmark finding, " Geschwind said. " It's no coincidence that a gene

linked to autism has a higher concentration in key brain regions that regulate

speech and the ability to interpret social interaction. Our research suggests

that CDH10 is switched on at a very early stage and plays an important role in

regulating the developing brain. This prenatal activity somehow makes the infant

more susceptible to autism. "

By influencing the development of important brain structures, CDH10 provides a

tangible link between genes, brain circuitry and a child's future behavior,

Geschwind noted. The discovery also opens up a number of intriguing next steps

for research, including the possibility of an imaging study to explore whether

the gene behaves differently in the autistic brain.

The DNA samples and clinical data were provided by families who donated blood to

the Los Angelesbased Autism Genetic Resource Exchange (AGRE), a program created

and funded by Cure Autism Now, which merged with Autism Speaks in 2007.

" When parents like me first formed AGRE, this was our dream, that talented

scientists would use our gene bank to collaborate and bring us closer to

understanding autism, " said Jon Shestack, co-founder of Cure Autism Now and a

board member of Autism Speaks. " AGRE has played an important role in almost

every major autism genetics paper in the past five years. "

Autism is a complex brain disorder that strikes in early childhood. The

condition disrupts a child's ability to communicate and develop social

relationships and is often accompanied by acute behavioral challenges. The

Centers for Disease Control and Prevention report that one in 150 American

children is diagnosed with an autism spectrum disorder; the disorder affects

four times as many boys as girls. The diagnosis of autism has expanded tenfold

in the last decade.

###

The UCLA portion of the study was supported primarily with funding from the

National Institute of Mental Health. Geschwind's UCLA colleagues included Brett

Abrahams, Rita Cantor, Hongmei Dong, Herman, Ted Hutman, Ana Alvarez

Retuerto, n Sigman and Sonnenblick.

Additional co-authors included scientists from the Children's Hospital of

Philadelphia, USC, Autism Speaks, the University of Pennsylvania, the University

of Miami, Mount Sinai School of Medicine, the University of Washington, the

University of North Carolina, UC , Yale University, the University of

Illinois, the University of Utah, Indiana University, Vanderbilt University and

the University of Pittsburgh.

The UCLA Center for Autism Research and Treatment provides diagnosis, family

counseling and treatment for patients with autism. UCLA is one of eight centers

in the National Institutes of Healthfunded Studies to Advance Autism Research

and Treatment network and one of 10 original Collaborative Programs for

Excellence in Autism.

For more news, visit the UCLA Newsroom.