Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Complex Gene Interactions Account for Autism Risk

04.08.2005


Using a novel analysis of the interactions among related genes, Duke University Medical Center researchers have uncovered some of the first evidence that complex genetic interactions account for autism risk. The Duke team found that the brain mechanism that normally stops or slows nerve impulses contributes to the disease.



The team’s findings implicate the so-called GABA receptor genes, which are genes that code for key components of "off switches" in the brain’s neurons. GABA, or gamma aminobutyric acid, is a neurotransmitter – a chemical that one neuron fires at receptors on another neuron to trigger a response – in this case an inhibitory response. GABA receptors are protein switches nestled in nerve cell membranes that are triggered by GABA to cause such inhibition.

Importantly, the study found that the GABA brain system most likely exerts its influence via complex gene-gene interactions.


The current findings, and others that might result from the team’s new approach, may ultimately point to methods for early diagnosis of autism, and perhaps new autism therapies, according to the researchers.

"Identifying the genes that contribute to cause autism has been challenging," said Margaret Pericak-Vance, Ph.D., director of the Duke Center for Human Genetics. "One explanation is that many genes are involved, none of which individually may have a major effect." At least ten genes – and possibly as many as a 100 – are hypothesized to be involved in autism, she said.

"In addition, autism may stem not from the effects of single genes, but rather from the interaction of particular genes, or sets of genes, when they come together in certain combinations," Pericak-Vance added. The analytical method applied by the researchers allowed them to rigorously test for the role of such gene combinations in autism for the first time, she said.

The researchers reported their findings in the September issue of The American Journal of Human Genetics (available online August 3, 2005). The work was supported by the National Institutes of Health, the National Alliance of Autism Research, and the Hussman Foundation. Resources were also provided by The Autism Genetic Resource Exchange, a program of Cure Autism Now.

In recent years, the number of children diagnosed with autism in the United States has skyrocketed, the researchers noted. One of the most heritable of complex genetic disorders in neuropsychiatry, autism is characterized by impairments in social interaction and communication and restricted and repetitive patterns of interest or behavior.

While many previous studies have identified possible genes with links to autism, there remains no single gene with a consistent connection to the disease, Pericak-Vance said.

Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in patients with autism, have implicated the brain mechanism in the disease. Furthermore, there is evidence that GABA plays a key role in the early development of the brain.

Earlier research by the Duke team and other researchers linked a portion of chromosome 15 to autism risk. That region harbors genes that code for three GABA receptors.

Since one of the primary functions of GABA is to inhibit nerve cells from firing, it plays a key role in telling the body to "slow down.". The GABA system therefore acts as a sort of information filter, preventing the brain from becoming over-stimulated, the researchers explained.

"Impairing the GABA system could overwhelm the brain with sensory information, leading to both the behavior and the pattern of cell damage that emerges in autism," said John Hussman, Ph.D., a study co-author and president of The Hussman Foundation, one of the groups that funded the study.

The researchers examined 14 genes that encode portions of the GABA receptor in 470 Caucasian families. Of those families, 266 included more than one person with autism and 204 included one autistic individual. The team tested for associations between particular gene variants and the disease. They also applied sophisticated statistical methods designed to zero in on the effects of particular gene combinations.

The researchers found that one of the GABA receptor genes, GABRA4, is involved in the origin of autism. Moreover, they report, GABRA4 appears to increase autism risk through its interaction with a second GABA gene, GABRB1.

"This is a key finding for our understanding of the complexity of interactions that underlie autism," Pericak-Vance said. "We can now apply the analytical approach to other genes that may play a role in the disease." Such findings may ultimately yield a method to screen for individuals at high risk for the disease, she added.

"The new findings offer important new information for families affected by autism about the complexity of the disease," said clinical psychologist Michael Cuccaro, Ph.D., a study co-author also of the Duke Center for Human Genetics.

Furthermore, he added, existing medications already target the GABA system, including diazepam (Valium®) and some anti-epileptic drugs. "As we begin to understand the GABA system as it relates to the neurological underpinnings of autism, we may advance toward new therapies."

Collaborators on the study include D.Q. Ma, P.L. Whithead, M.M. Menold, E.R. Martin, A.E. Ashley-Koch, G.R. DeLong and J.R. Gilbert, all of Duke; H. Mei of North Carolina State University; M.D. Ritchie of Vanderbilt University; and H.H. Wright, Ruth Abramson of University of South Carolina.

Kendall Morgan | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>