“Such sporadic mutations may be behind a large fraction of autism cases,” which may explain the increased incidence of autism in offspring of fathers

(parents) having children later in life.


Rutgers to Create Autism DNA Repository to Study Sporadic Germ-Line Mutations


By a GenomeWeb staff reporter


NEW YORK (GenomeWeb News) — Rutgers University’s Cell and DNA Repository will use a $7.8 million grant from a private foundation to establish a new collection of DNA samples to help autism researchers study sporadic germ-line mutations linked to the disease, Rutgers said today.

The Simons Foundation hired RUCDR through its Autism Research Initiative to establish the Simons Simplex Collection, which will house samples from 2,000 families who have a single autistic child.

The 2-year program will obtain blood samples from 8,000 participating family members from 11 different centers in the US and in Canada and send them to Rutgers where they will be processed into DNA and cell lines and stored.

The collection “will constitute the core resource for a new and different line of research into the genetics of autism,” said Jay Tischfield, RUCDR’s scientific director.

The Simons Simplex Collection is designed to help researchers studying genetic alterations in the sperm or eggs — but that are not found in other tissues — in parents of autistic children. “Such sporadic mutations may be behind a large fraction of autism cases,” Rutgers said, which may explain the increased incidence of autism in offspring of parents having children later in life.

Tischfield said the study will look into the link between the high frequency of large DNA deletions present in autism cases where only one child in a family is affected. Tischfield added that in families that present more than one or even several autistic children “there is probably a defect in a gene that is inherited in the usual sense” rather than a sporadic mutation.

In a statement, 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,” he said.

“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.

The Simons Simplex Collection is establishing new 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.”

The Simons Foundation is a New York-based non-profit focused on basic research in the sciences, with an emphasis on autism research. It also is a benefactor for Yale University, Cold Spring Harbor Laboratory, the Massachusetts Institute of Technology, and other research institutes.