This is a competitive renewal of our program project to dissect the genetics of neurological diseases. During the first four years of the most recent funding period, we have made significant progress in each of our projects, and published 53 papers and have 3 in press. With this resubmission, we will focus our attention completely on the difficult and very important problem of the genetics of autism, one of the most common neurodevelopmental disorders. To do this, we will integrate the latest in genetic and genomic technologies with detailed clinical assessments. """"""""Genetic Studies in Autism on Chromosome 7,"""""""" is a continuation of efforts from the current Program Project. We will examine in detail the most consistently identified chromosomal region in autism, 7q21-32. We will apply three complementary approaches that include a comprehensive SNP scan of the region, specific testing of the REELIN gene, and characterization of the translocation breakpoints identified in an autism multiplex family. """"""""Restricted and Repetitive Behaviors in Young Children with Autism"""""""", will characterize the extent and trajectory of a critical behavioral aspect of autism. Understanding the emergence and trajectory of these behaviors has significant implications for directing interventional treatment. """"""""Neurogenetics of Candidate Systems in Autism"""""""" will use a functional candidate approach to determine the role(s) of genes underlying the serotonin and GABA systems, two systems known to affect behaviors exhibited by autistic children. We will characterize the variation in each gene using a comprehensive set of SNPs defining haplotype blocks, and examine their potential role individually and jointly in autism and in specific subsets of autistic behavior. An administrative core, a clinical and bioinformatics core, and a molecular analysis core will serve these three Projects. This integrated approach toward autism will provide significant insight into the role that specific genes play in this complex genetic disorder.
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