Saturday, May 9, 2009: 11:00 AM
Boulevard (Chicago Hilton)
Rapid progress is being made on a number of fronts with regard to understanding the etiologies that underlie the autisms. The autisms are among the most common of neurodevelopmental disorders, and are highly heterogeneous in disorder phenotype, longitudinal trajectory of symptoms and response to treatment. A brief overview of the current state of thinking regarding the genetic and environmental risk factors will be discussed. Work from our own laboratory will be the focus of the remainder of the lecture. The convergence of human genetics in autism and basic developmental neurobiology studies suggests that the MET receptor tyrosine kinase signaling is important for the proper assembly of forebrain circuits, particularly those involving cortical projection neurons in which MET is heavily expressed. Dysregulation of MET signaling leads to alterations in cellular morphology, synapse development, and functional disruptions in both model systems and in humans. Multiple, convergent human genetic data implicate this signaling pathway as a major risk factor for autism. First, our laboratory discovered that a single nucleotide polymorphism in the 5’ regulatory region of the human MET gene is associated with autism. Second, there has been replication in 6 different family cohorts, plus identified copy number variants (CNVs) and rare mutations in the MET gene, and association with autism of two other genes in the MET signaling pathway. Third, certain single gene, syndromic disorders with high a prevalence of autism also involve this same cellular signaling pathway. Fourth, the MET promoter variant is functional, as it reduces gene transcription. Fifth, studies of human postmortem samples show that MET and other upstream molecules that regulate MET signaling are dysregulated in autism. A model of autism etiology will be presented in light of the basic and clinical research findings.
See more of: Molecular Genetics of Autism
See more of: Invited Educational Symposium
See more of: Invited Education Symposia, Keynote Speakers, Awards
See more of: Invited Educational Symposium
See more of: Invited Education Symposia, Keynote Speakers, Awards