Daniel H. Geschwind, M.D., Ph.D. MIND Institute Distinguished Lecturer Series: October 13, 2004 Biography Daniel H. Geschwind, M.D., Ph.D., is professor of neurology at UCLA, where he also directs the Program in Neurogenetics and the Center for Autism Research and Treatment. Dr. Geschwind’s research focuses on the genetic bases of human cognitive specializations and their relationships with disease processes, such as autism and focal neurodegenerative syndromes, using molecular genetic and neurobiological approaches. During the last 5 years, his research has increasingly emphasized autism and working with the Autism Genetic Resource Exchange, a resource of publicly available biomaterials and data for which he provides scientific oversight. Dr. Geschwind is a graduate of Dartmouth College and the Yale University School of Medicine. Presentation Abstracts Molecular Genetics Studies of Autism: Endophenotypes and the challenges of heterogeneity (4PM) Genetic and phenotypic heterogeneity provide significant challenges to positional cloning of autism susceptibility genes. We have approached this problem by ascertaining large sample sizes and trying to identify heritable endophenotypes that may be more directly related to genetic factors predisposing to autism. One of our focuses has been language-related endophenotypes, since language is such a fundamental human specialization. We have used quantitative trait methodologies to identify speech and language related loci in a large autism cohort with some preliminary success. We have also begun to use other quantitative methods, such as the social reciprocity scale (Constantino), to use QTL analysis directed at other core autism-related features. We have also begun to explore large-scale association studies focusing on candidate pathways, and dense SNP mapping under regions of linkage, so as to identify the underlying mutational basis of autism. Autism, Genes and the Environment (6PM) Autism is the most heritable neuropsychiatric condition, but its genetic foundation is complex. Many genes and the environment underlie autism susceptibility. How one uses genetics to understand a disease like autism and how this can help us further understand complex environmental effects will be discussed. The role of shared resources and large collaborations, such as the Autism Genetic Resource Exchange will also be discussed.