INFRASTRUCTURE TO FACILITATE DISCOVERY OF AUTISM GENES

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DESCRIPTION (provided by applicant): Autism is most likely inherited by an oligogenic mechanism with epistasis. Thus, large samples will be required to locate the contributing genes, and a number of complementary methods will be needed. Genome screens of sib pair families have identified a few consistent chromosomal regions of interest, but there are numerous other suggestive signals that need to be verified in much larger samples. The purpose of this application is to facilitate the discovery of the genes that contribute to autism, by developing and maintaining an infrastructure by which research groups studying the genetics of autism can work collaboratively. This will be accomplished through workshops, a Virtual Private Network (VPN), and access to a database that includes phenotype and genotype data from all participating groups. Other goals are to develop and continually update information on autism genetics for families and practitioners. There will be substantial quality control to assure the accuracy of the data. The six groups participating in this application have been working together for 18 months toward the goal of establishing an effective means to share data. Any new group may join at any time, as long as their data meet the volume and quality standards described in the application. The current groups are the Collaborative Linkage Study of Autism (Tufts/New England Medical Center, University of North Carolina at Chapel Hill, Vanderbilt University and the University of Iowa); Duke University and the University of South Carolina; Mt. Sinai Medical Center in New York and Trinity University in Dublin, Canadian Autism Genetics (McMaster University, and the University of Toronto/Hospital for Sick Children); Stanford; the Paris Autism Research International Sib-pair Study (INSERM in Paris and Creteil. Goteborg University in Sweden, Ben-Gurion University in Israel and Hebrew University of Jerusalem in Israel). Currently, our collective sample numbers nearly 800 sib pair families and also includes cousin pairs and connecting relatives, uncle/nephew and father/offspring pairs, trios (one proband and both parents). We expect that having a forum (both virtual - the VPN and database, and actual - the workshops) where information can be shared openly and easily will facilitate the discovery of genes contributing to the cause of autism. The database will contain large numbers of families and a wealth of phenotype data which will allow the drawing of sub-samples based on a common phenotype, such as macrocephaly, absence of functional language, absence of any structural language abnormality, or prominence of resistance to change.