For several years, several child and adolescent onset disorders, including autistic disorder, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and major depressive disorder, have been shown to have varying degrees of genetic influence. However, there has been no consistent evidence that they are explained by single genes, or by genetic factors alone. Recent developments in molecular and statistical aspects of genetics have made the study of such complex disorders feasible. The first research component of the independent scientist award is to collect 350 carefully diagnosed subjects with autistic disorder. The Autism Diagnostic Interview and Autism Diagnostic Observation Schedule will be used in addition to diagnosis of autistic disorder by both the examining child and adolescent psychologist and child and adolescent psychiatrist. Cross-site reliability will be maintained. DNA will be collected from both the proband and his/her parents. The transmission/disequilibrium test (TdT) will be used to determine whether alleles at candidate loci are preferentially transmitted. In addition, this data base will be available for replication of any susceptibility loci identified in other samples. In a previous study, linkage disequilibrium between attention-deficit/hyperactivity disorder and a genetic marker at the dopamine transporter locus has been identified. A second research component of the independent scientist development plan will be a study designed to replicate the initial study with addition of a structured diagnostic interview. In collaboration with other colleagues, genetic analyses of childhood onset major depressive disorder (TdT of candidate genes) will be conducted. An emphasis will be placed on collecting DNA from subjects with reliably and valid diagnoses to provide a data base for molecular genetic studies severe disorders of children and adolescents. Consultants in diagnostic methodology and genetic analysis will meet regularly with the candidate to provide guidance for ongoing research career development.
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