The Simons Foundation, through its Autism Research Initiative, has signed a $7.8 million, two-year contract with the Rutgers University Cell and DNA Repository (RUCDR) to establish a collection of DNA samples for autism studies. The samples will be collected from 2,000 families that have a single autistic child.
"The Simons Simplex Collection, as this project is known, will constitute the core resource for a new and different line of research into the genetics of autism," said RUCDR Scientific Director Jay Tischfield, who is also the Duncan and Nancy MacMillan Professor of Genetics at Rutgers. "We will be looking not only at autism that is passed from generation to generation, but also at autism that derives from 'sporadic' genetic changes that may occur within one generation. It is now recognized that such sporadic mutations may account for a large fraction of autism cases."
Blood samples from the 8,000 participating family members will be collected at 11 centers around the United States and Canada, and shipped to Rutgers for processing into DNA and cell lines that will then be preserved and stored in vaults of liquid nitrogen. Autism researchers will be able to access these genetic specimens through the auspices of the Simons Foundation.
"We are proud to have been chosen by the Simons Foundation to construct and maintain this unique and unprecedented resource, a tool that can help unlock some of the mysteries of autism," said Richard L. McCormick, president of Rutgers, The State University of New Jersey. "The opportunity to contribute to this initiative is due in great measure to the leadership position that Rutgers scientists have achieved in the field of medical genetics."
Autism is a disorder that manifests early in life and has no known cure. It is tied to a child's early brain development and is usually diagnosed in the first three years of life.
Autistic children typically have difficulties with behavior, social interaction and communications skills; but there is a broad spectrum of symptoms and characteristics, expressed in combinations from extremely mild to quite severe.
Most scientists agree that there is a genetic basis for autism, with an assortment of environmental factors possibly conspiring with the altered genes to produce the many forms of the disorder. Many believe that genetic analyses will point the way for future research and potential therapies.
The Simons Simplex Collection will supply the groundwork for a different approach to autism genetics. The strategy is based on the premise that new genetic alterations occur in the germ line (sperm or eggs) of one of the parents, but they are not found in other tissues of the parents. Such new or "sporadic" mutations may account for a large fraction of autism cases. They may also explain why the incidence of autism increases with parental age.
Tischfield said that, in general, there may be several different kinds of genetic deficiencies in autism and that many cases may not be due to mutations that are passed on from generation to generation, as in other disorders , such as cystic fibrosis or hemophilia. Consistent with this, geneticists are finding that in sporadic autism cases, where there are no other affected children, there is a high frequency of relatively large, new DNA deletions that are probably not inherited.
"You do not find them in the parents - and that is the key," Tischfield said. To find individuals with sporadic mutations the project will seek out families with only one affected child. In a family where several children display autism, there is probably a defect in a gene that is inherited in the usual sense.
Clinicians and scientists working with the Simons Simplex Collection are establishing new and rigorous diagnostic criteria to ensure that the selected individuals represent this sporadic type of autism. Molecular tests will eliminate individuals with other diseases that might mimic autism, such as fragile X syndrome - the most common cause of mental retardation in males.
"The genetic bases of this new autism mechanism are only distinguishable with novel technologies, and that is why we missed them in the past," Tischfield said.
"Ultimately, we want to determine the mechanism that is responsible for these mutations and how the deletions cause autism," he added. "this understanding will give us a better idea of genes involved in brain development and could lead to better treatment in the short term and, possibly, prevention in the future."