SALT LAKE CITY - In an autism study of unparalleled size and scope, the Autism Genome Project (AGP), a worldwide consortium of leading researchers from the University of Utah School of Medicine and 50 other institutions, has identified a gene that may predispose people to autism.
The neurexin 1 gene belongs to a family of genes believed to be important for developing contact and communication between neurons, the nerve endings that allow various parts of the brain to send and receive signals. AGP researchers identified the region that includes a gene called neurexin 1 by combining two methods of gathering genetic data-putting thousands of gene markers on microchips and then analyzing the information to look for common genetic traits of autism spectrum disorders and by searching for variations or mutations in DNA coding contained in genes possibly associated with the disorder. The group also identified a previously unidentified region on chromosome 11 that may contain another gene related to the mysterious brain disorder.
Funded by Autism Speaks, a national non-profit dedicated to increasing awareness of autism and raising money to research the disorder, and the National Institutes of Health, the preliminary findings from the AGP's first phase were published online today by Nature Genetics and also will be published in the magazine's March print edition.
William M. McMahon, M.D., professor of psychiatry at the School of Medicine and one of two Utah co-investigators in the study, said identification of the chromosomal region containing neurexin 1 is an encouraging step to understanding autism. Hilary Coon, Ph.D., research professor of psychiatry at the University, is the project's other Utah co-investigator.
"This finding helps us focus our efforts on specific gene known to play a role in brain development," Coon said. "We'll be using some of these new techniques in our ongoing studies in other Utah families."
Autism is a complex brain disorder that impairs social, communicative, and behavioral development and often is characterized by extreme behavior. A recent study from the U.S. Centers for Disease Control looked at autism in 14 states, including Utah, and found the disorder to be 20 times more prevalent than two decades ago. Utah had the third highest rate of autism-one in 133 children-of the 14 states surveyed.
The recent prevalence study showed autism to be 20 times more frequent in Utah than was estimated in the UCLA-University of Utah Autism Epidemiology Study conducted in the 1980s. McMahon and others have begun contacting the adults who were children in the study 20 years ago. "We believe many of the children who did not meet autism diagnostic criteria 20 years ago, may meet current criteria," McMahon said. "This may help us understand why autism prevalence is higher and we'd like to test genes such as neurexin 1 in these adults."
People who wish to volunteer for this and other genetic studies can call the Utah Autism Center at (801) 585-9098.
In 2002, more than 120 AGP researchers from 19 countries began gathering DNA samples from autistic individuals in nearly 1,200 families. The DNA was placed on microchips, enabling scientists to compare 10,000 DNA markers and identify chromosome regions shared among people with autism, a technique called linkage. Researchers also scanned DNA from these families to look for copy number variations (CNV)-additions or deletions in genetic coding that may well be linked to autism and other disorders and diseases.
The goal was to identify genes that make people susceptible to autism. By combining information from the gene chip technology and CNV, added to the unprecedented statistical power provided by the uniquely large genetic sample, the researchers identified neurexin 1 as a possible susceptibility gene. Other genes in that region of chromosome 11, and throughout the entire genome, also may make good candidates for susceptibility genes and will be examined in the studys second phase.
Andy Shih, Autism Speaks chief science officer, said the innovative combination of gene chips and CNV were critical in focusing on neurexin 1 and potentially other genes that may make people susceptible to autism. Identifying these genes can lead to breakthroughs in diagnosing and treating patients and in supporting families.
"By combining cutting-edge CNV analysis with more traditional linkage and association (analyses), the scientists now have a promising new framework to look for autism susceptibility genes," Shih said. "These exciting findings from the AGP linkage scan confirm the value and contribution of multidisciplinary collaboration to advancing autism research."
In phase two of the AGP, beginning soon, researchers will expand use of gene chip technology to search the genome for new genetic markers of autism, as well as search chromosomes for copy number variations associated with autism spectrum disorders. To do this, the AGP will use high throughput DNA sequencing, a technique that allows researchers to look at vast numbers of DNA sequences to pinpoint underlying changes in autism susceptibility genes.
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William M. McMahon, M.D., professor of psychiatry
(801) 585-7781 (office); (801) 718-4109 (cell)
(Dr. McMahon can be reached on his cell this weekend.)
Phil Sahm, University of Utah Health Sciences Public Affairs
(801) 581-2517 (office)
(801) 419-8512 (cell)