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Recruiting Families, Recruiting Researchers

Connie Anderson, Ph.D.
IAN Community Scientific Liaison
Date Published: 
April 12, 2011

"If you know one person with autism, you know one person with autism," people familiar with the condition will say. They are acknowledging how different autism spectrum disorders (ASDs) can look in the wide variety of individuals who bear that label. A person with an ASD may be able to talk or unable to talk, socially aloof or socially interested, have a very low IQ or a very high IQ. How do we ever figure out what is behind all this variety? How do we ever figure out what causes ASDs?

Strand of DNA in blue and yellowPart of the answer is that we are beginning to understand that we're not dealing with just one condition or one cause. There are likely many conditions that appear similar but have varied causes. The quest to identify different types of autism based not on outward behavior, but on differences in genes, brain structure, and the like, has become a major goal of autism research. 1 2 3

The Simons Simplex Collection: Partnering with Families to Search for the Source of ASD

It was with this in mind that the Simons Foundation set out to create the Simons Simplex Collection (SSC). 4 They hoped to study a large number of simplex families, that is, families with only one child with ASD. Other projects were studying families with more than one child on the autism spectrum, but it seemed clear that most cases of ASD were not inherited directly from parents, but arose "out of the blue." It was exactly this fact -- that a child was different from other family members -- that would make it possible to take DNA samples from all of them and then compare. What was different about the child with ASD? What story did his or her DNA tell compared to the story told by the DNA of parents and siblings?

To create the Simons Simplex Collection (SSC), the Simons Foundation planned to recruit 2,000 families with just one child on the autism spectrum and a significant number of autism-focused researchers. They started with the latter, forming a coalition of thirteen experienced autism research centers located at the following universities:

  • Baylor College of Medicine
  • University of California, Los Angeles (UCLA)
  • Columbia University
  • Emory University
  • Harvard University/Children's Hospital - Boston
  • University of Illinois
  • Michigan University
  • McGill University
  • University of Missouri
  • Vanderbilt University
  • Washington University
  • University of Washington
  • Yale University

Each site's Simons Simplex Collection team was led by an expert in genetics and a clinical psychologist. Rigorous training was conducted so that staff at all of these sites would perform and interpret autism diagnostic and other tests in the same way. When one site's information looked a bit different from all the other sites' information, it was decided that the families participating at that site would be evaluated again. This would be expensive and time-consuming, but necessary to make sure the information from every study site was as accurate and consistent as possible.

Each site was responsible for recruiting families locally who met strict guidelines. Families had to have only one child with ASD between the ages of 4 and 17, an unaffected child in the same age range, and no cases of ASD in their extended family. In addition, the child's ASD had to be unexplained. Children with a known condition like Fragile X syndrome were excluded, and so were children who had suffered any major problem before or during birth that might be responsible for some of their challenges. Families could only be part of the study if both mother and father agreed to participate.

As of February 2011, more than 2,600 families have been recruited from the geographic areas around the thirteen Simons Simplex Collection sites. Recruitment will be ongoing through the spring of 2011.

Each volunteer family generously gives their time and energy for the sake of science and people with ASDs everywhere. The children with ASD undergo a thorough assessment, including an autism evaluation using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview -- Revised (ADI-R) -- both "gold standard" instruments for autism diagnosis. Many other aspects of the children's functioning also are measured, including IQ, language skills, and motor skills. Parents participate in lengthy interviews to provide pregnancy, medical, and developmental histories, as well as accounts of their child's past and current behavior.

The Tiniest Puzzle Pieces

One key goal of the Simons Simplex Collection project is to identify very tiny genetic changes in the children with ASD not shared by their family members.

Recent research has shown that some individuals with ASD have extra genetic material or are lacking genetic material. Instead of the usual two copies of every gene, they may have one copy, three copies, or none at all. What's more, it is often not just one gene that is "duplicated" or "deleted," but a whole set of neighboring genes. When this happens, it's called a copy number variation or CNV. 5 6 7 There's nothing wrong with the genes themselves -- they are normal. It's just that there are too many or too few of them, and so they are doing too much or not enough of whatever it is they are supposed to do.

CNVs are rare, but there may be many different CNVs playing a role in autism. All together, they may explain a large number of autism cases. Researchers can't put the larger autism puzzle together without identifying each tiny piece, and CNVs are very important ones.

Seeds and Flowers: Genes and Different Types of ASD

A brilliant yellow sunflowerAnother challenge in autism research is figuring out what genetic changes lead to what kinds of ASD. For example, one set of genetic changes might lead to a child with ASD plus delayed speech and gastrointestinal (GI) issues, while a different set of genetic changes might result in a child with high-functioning ASD and anxiety.

To do a good job connecting the dots from a certain genetic change to a type of ASD, you have to be very sure you've done a good job describing everything about a person and family. The task is like matching certain kinds of seeds to the flowers they become. You have to be sure you've done a good job describing both seeds and flowers or you won't get far. That is why families participating in the Simons Simplex Collection not only provide blood samples for DNA analysis, but also undergo extensive interviews and diagnostic work-ups focusing on past and current behavior and challenges.

Researchers talking about this say they need to link genotype to phenotype. They mean they want to see which genetic changes (think of seeds) result in what set of ASD traits in a person (think of flowers). Researchers in a new program called the Simons Variation in Individuals Project 4 are already investigating a number of CNVs associated with genes on chromosome 16 because these have been found frequently in ASD. 8 They will study whether people with these CNVs are alike in other ways as well.

Researchers also will want to see if varied genetic changes are involved in similar processes. What if many different CNVs have a similar end result, like affecting how various parts of the brain communicate with each other? That would be a major clue to what is going on in autism.

A Major Scientific Resource, Now and in the Future

The Simons Simplex Collection project demonstrates how a partnership between dedicated researchers and committed families can result in a unique collection of vital autism information. Now Simons Simplex Collection DNA and other data are being made available to all kinds of qualified autism researchers. Many studies investigating CNVs (the "tiniest puzzle pieces"), genotype and phenotype ("seeds and flowers"), and other topics will be possible that were not possible before. The Simons Simplex Collection's contributions to autism science have just begun.

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Additional Resources: 
  • Rutter, M. (2000). Genetic studies of autism: From the 1970s into the millennium. Journal of Abnormal Child Psychology, 28(1), 3-14. View Abstract
  • Viding, E., & Blakemore, S. J. (2007). Endophenotype approach to developmental psychopathology: Implications for autism research. Behavior Genetics, 37(1), 51-60. View Abstract
  • Volkmar, F., & Klin, A. (2005). Issues in the classification of autism and related conditions. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (pp. 5-41). Hoboken, NJ: John Wiley & Sons.
  • Fischbach, G. D., & Lord, C. (2010). The Simons Simplex Collection: A resource for identification of autism genetic risk factors. Neuron, 68(2), 192-195. View Abstract
  • Christian, S. L., Brune, C. W., Sudi, J., Kumar, R. A., Liu, S., KaraMohamed, S., et al. (2008). Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biological Psychiatry, 63(12), 1111-1117. View Abstract
  • Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., et al. (2007). Strong association of de novo copy number mutations with autism. Science, 316(5823), 445-449. View Abstract
  • Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. The New England Journal of Medicine, 358(7), 667-675. View Abstract
  • Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., et al. (2008). Recurrent 16p11.2 microdeletions in autism. Human Molecular Genetics, 17(4), 628-638. View Abstract