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

[September 6, 2007]

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.

A relevant link from the Simons foundation page
http:// simonsfoundation.org/page.php?id=96 (link broken)

The Simons Simplex Collection (SSC) is a core project and resource of the Simons Foundation Autism Research Initiative (SFARI).  The primary goal of the SSC is to establish a permanent repository of genetic samples from 2000 families, each of which has one child affected with an Autism Spectrum Disorder (ASD) and parents unaffected with ASD.  Each genetic sample will have an associated collection of data that provides a precise characterization of the individual (phenotype).  Rigorous phenotyping will maximize the value of the resource for a wide variety of future research projects into the causes and mechanisms of autism.  The Simons Simplex Collection is operated by SFARI in collaboration with eleven university-affiliated research clinics (see below).  The clinics will identify and assess potential SSC subjects, with guidance from the University of Michigan Autism & Communication Disorder Center (UMACC), to ensure uniformity across clinics.

Previous pioneering efforts to collect genetic samples focused on families with multiple individuals affected with ASD, most notably the Autism Genetic Resource Exchange (AGRE), which is an ongoing effort to identify such multiplex families.  The SSC differs from those efforts in its focus on simplex families, and in its clinic-based assessment and diagnosis.

The initial collection period to identify 2000 families is slated to last for two years.

The Simons Foundation has committed roughly $6 million of its Autism Research Initiative funds for the first year of operation of the Simplex Collection.
The current collaborating institutions are Columbia, Emory, Harvard, McGill, UCLA, University of Illinois - Chicago, University of Michigan, University of Washington, Vanderbilt, Washington University, and Yale.

Blood samples will be processed into cell lines and DNA at the  Rutgers University Cell and DNA Repository (RUCDR). Stored samples will be freely available to SFARI grant holders, and to other researchers on a modest fee-for-use basis.  

Data will be collected and managed using software developed by Prometheus Research, LLC. A central database characterizing all of the study subjects (with identifying information removed) will be available to any qualified researcher through a web interface.

Participants in the SSC project  communicate and manage the project using online collaboration software called Basecamp.

For further information concerning the SSC, please  contact the Simons Foundation.

Basically, my reading of this is that they will make cell lines from the blood of 200 families where one person has autism.  They don't explicitly state who contributes the blood, but the hypothesis they want to test, namely, that autism might arise from genetic deletions randomly occurring in a sperm or egg, requires that the DNA of the autistic person (I'm guessing in most cases, this would be a child--they state as much) is compared to that of the parents.

They're going to create a resource of cell lines and DNA, along with "rigorous phenotype" information about the donors that autism researchers will have access to for a fee.  They will remove the identifying information (i.e. who the donors are) but include the phenotype information (which they don't say what info they plan to collect) with the DNA.

The idea would be to try and identify possible autism-associated variations in the DNA, presumably by comparing the DNA of the autistic person with that of his or her parents.  (Note:  the vast majority of the DNA of the child should be identical to the DNA of the parents, given the way heredity works.) What they'll be looking for, I gather, is areas of chromosomes where DNA that is present in the parents is missing in the child (called a "deletion").

I'd be interested in knowing what kind of consent form was signed by the families.  Children really can't consent--parents make this decision on their behalf.  Are there restrictions on the use to which this DNA might be put?  How would this be enforced?  Who has, or should have, access to the information?