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NIH and Autism Advocacy Organizations Partner on Genetic Susceptibility Research

October 08, 2007

A $10.8 million public-private partnership of government health agencies and private advocacy organizations has issued five research awards for funding over the next five years to advance research into the genes associated with Autism Spectrum Disorders. Cure Autism Now is proud to participate in this historic partnership, in which the Autism Genetic Resource Exchange (AGRE) will play a key role.

"This public-private partnership is a wonderful example of how the entire autism community can and should band together to overcome autism," says Peter Bell, CEO of Cure Autism Now. "We are pleased to partner with the NIH and two other leading autism organizations to get to the root of autism, so we can begin the process of helping our children who suffer from autism and prevent future generations from developing the disorder."

The National Institutes of Health (NIH) is spearheading the coalition, whose members include the National Institute of Mental Health (NIMH), National Institute for Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communications Disorders (NIDCD), the National Institute of Child Health and Human Development (NICHD), and the National Institute of Environmental Health Sciences (NIEHS). The private nonprofit organizations that complete the partnership are Cure Autism Now (CAN), the National Alliance for Autism Research (NAAR) and the Southwest Autism Research & Resource Center (SARRC).

There is strong evidence from twin and family studies of a high heritability component to autism. However, the genetics are complex and, to date, no simple model or single gene can easily explain all cases of autism. The current theory is that genetic susceptibility may be caused by multiple genes that can act in concert with environmental factors. The importance of identifying contributing genes, even if they may each account for only a small fraction of the autism susceptibility, is that it can point directly to the crucial underlying biochemical pathways that are malfunctioning, opening up strategies for rationale treatment design.

"The key really is in identifying the protein functions that have been disrupted. This gives us the ability to develop treatments to overcome those impairments," says Sophia Colamarino, Ph.D., Science Director of Cure Autism Now.

Although there are reports of several chromosomal regions associated with the disorder, few specific genes have been identified. The goal of the coalition is to advance knowledge of the relation between genetics and autism by examining existing data for genes and gene variants that confer susceptibility to autism. Researchers will also be assessing the functional significance of autism-associated genetic variants. This research may provide a means to subdivide Autism Spectrum Disorders into identifiable, distinct disorders with different molecular mechanisms.

More than 25 applications were received in response to the request for applications, titled "Identifying Autism Susceptibility Genes." The five awards issued by the coalition are:

  • "Identification and Functional Assessment of Autism Susceptibility Genes," Dr. Linda Brzustowicz, Department of Genetics, Rutgers, The State University of New Jersey at New Brunswick
  • "Identification and Functional Assessment of Autism Susceptibility Genes," Dr. James Millonig, Department of Neuroscience & Cell Biology, University of Medicine and Dentistry of New Jersey, the Robert Wood Johnson Medical School
  • "Identification and Functional Assessment of Autism Susceptibility Genes," Dr. Veronica Vieland, Center for Statistical Genetics Research, University of Iowa
  • "Determining the Genetic Basis of Autism by High-Resolution Analysis of Copy Number," Dr. Jonathan Sebat, Cold Spring Harbor Laboratory
  • "Identifying Autism Susceptibility Genes by High-Throughput Chip Resequencing," Dr. Michael Zwick, Department of Human Genetics, Emory University

Drs. Brzustowicz, Millonig and Vieland have formed a collaboration that will take advantage of the powerful genetic repositories maintained by the NIMH and Cure Autism Now's Autism Genetic Resource Exchange (AGRE). The raw data to be studied comes primarily as a result of the Autism Genome Project 1, another collaborative effort that was launched three years ago by NAAR in order to provide genetic researchers with material to use in their studies. In this current project, genetic information on these families will now be analyzed using a new type of statistical analysis, known as Posterior Probability of Linkage (PPL), which is a particularly useful tool for detecting genetic linkage in large heterogeneous samples. Ultimately, any genetic difference identified by the team will be studied for their functional significance.

Instead of looking for changes in individual DNA bases, Dr. Sebat will search the genetic material from 500 families in the AGRE collection for regions of DNA that have either been deleted or repeated. These variations are known as Copy Number Polymorphisms (CNPs), as they can result in changes in the number of functional copies of a given gene. Upon identification of CNPs, Dr. Sebat will then work directly with AGRE to study the specific clinical features of families with unique CNPs. In doing so, he hopes to be able to determine subtypes of autism.

Taking a completely different approach, Dr. Zwick plans to focus his search for autism susceptibility genes on the X chromosome because of the high male to female ratio in autism. His group will identify sequence variations in promising loci, and will be looking especially closely at the gene that is responsible for Fragile X disorder, FMR-1. Fragile X is a common cause of mental retardation in which more than 20 percent of those diagnosed also meet the DSM IV criteria for autism. It is hoped this approach will yield insight into possible genetic elements that are responsible for the autism susceptibility shared by both disorders.