Feb. 19, 2007

Largest DNA scan for familial autism finds two genetic links

ANN ARBOR, Mich.—University of Michigan autism researchers and their colleagues at 50 institutions announced this week in the journal Nature Genetics initial findings from the largest genome autism scan yet completed.

Over the past five years, 120 scientists from around the world created the Autism Genome Project, assembling a massive DNA bank and conducting a comprehensive genome scan to find the genes that cause autism. Researchers have now begun a three-year, $14.5 million second phase to apply "gene chip" technologies to scan the genomes for association with new genetic markers.

"This a great example of many competing groups of scientists agreeing to come together to do analyses they couldn't have done on their own," said Catherine Lord, director of the U-M Autism and Communication Disorders Center.

The Autism Genome Project collected DNA from families with two or more children with Autism Spectrum Disorder—representing less than 10 percent of children with autism. These families are particularly interesting to geneticists focused on finding out what patterns are passed from parents to children.

U-M announced last month that it is leading a separate 11-university consortium to begin the new Simons Simplex Collection Autism Research Initiative, with the goal of gathering and banking DNA samples from 2,000 to 3,000 autism patients from families with one child with autism.

The Simons Simplex Collection is searching for new mutations that might cause autism, each one of which would have a large effect. The Autism Genome Project is looking for mutations that may be passed on from one generation to the next. Individual mutations, in the families with more than one child with autism, likely interact with each other, all contributing to the inheritance of the disorder. While the two projects have different goals, many researchers, including U-M's, are involved with both.

"Several of the same sites are involved in the Simons Simplex Collection project in which they will be identifying new families," Lord said. "They will continue to be involved in the Autism Genome Project.

"The measures used to diagnose autism and to describe the children in each sample are the same so it will be possible to compare the samples. All of us (involved with both projects) are also working to find better ways of identifying subtypes of autism in both groups (multiplex families and families with one child with autism) using the same methods."

For the Autism Genome Project, U-M recruited families with more than one child with autism from Michigan and nearby states, asking many local families to share their time (and blood samples) to participate in this study. The U-M autism center has subsequently organized an annual meeting of families with more than one child with autism so that they can meet each other and as a way to thank them for their time.

U-M also has worked with other researchers for many years to help develop "gold standard" measures for diagnosis allowing the data from the various sites to be analyzed together. Prior to the existence of these measures, it would not have been possible to combine samples across different sites because each of them would have been using different criteria for who had autism.

"Our biggest involvement is that AGP is using diagnostic measures (a parent interview and an observation of the child) that we designed along with colleagues in the United Kingdom and the United States," Lord said. "We are just one of many sites that recruited families and sent samples."

Autism Speaks, a nonprofit organization dedicated to increasing awareness of autism and raising money to fund autism research, the National Institutes of Health and several other international medical research organizations funded the effort.

The consortium leveraged the unprecedented statistical power generated by its unique sample set by using "gene chip" technology to look for genetic commonalities in individuals with autism culled from nearly 1,200 families.

The innovative combination of these two approaches implicates a previously unidentified region of chromosome 11 and neurexin 1, a member of a family of genes believed to be important in neuronal contact and communication, among other regions and genes in the genome.

The neurexin finding, in particular, highlights a special group of neurons called glutamate neurons and the genes affecting their development and function, suggesting they play a critical role in autism spectrum disorders.

"By combining cutting-edge analysis with the more traditional linkage and association, the scientists now have a promising new experimental framework to look for autism susceptibility genes," said Andy Shih, Autism Speaks chief science officer. "These exciting findings from the AGP linkage scan confirm the value and contribution of multidisciplinary collaboration to advancing autism research."

Lord, a nationally known pioneer in autism research, played a key role in learning how to properly diagnose two-year-olds a decade ago and is making new gains diagnosing young children at the U-M center.

While medications have helped with related conditions such as depression and hyperactivity, the best way to deal with autism is to intervene as early as possible to treat the condition, she said. Although individuals with autism continue to learn throughout their lives, progress in the very early years may set the stage for more rapid and general improvements in this disorder that, based on the latest estimates of the Centers for Disease Control, appears to occur in more than one out of every 200 children, Lord said.

Autism is a complex developmental disability that typically appears during the first three years of life. Autistic spectrum disorders affect the normal development of the brain processes related to social interaction and communication skills. Children and adults with autism typically have difficulties with verbal and nonverbal communication, social interaction and leisure or play activities.

For more information about participating in the research studies, call the center at (734) 936-8600.

Related Links:

U-M Autism and Communications Disorders Center

Autism Speaks

Contact: Joe Serwach
Phone: (734) 647-1844

Related Categories: Health

Related Keywords: autism, DNA, genetic links