This application for continued support of Years 21 through 25 of the Mental Retardation and Developmental Disabilities Research Center (MRDDRC) at the Kennedy Krieger Institute and Johns Hopkins University is submitted in response to RFA-HD-07-012. The MRDDRC consists of the Administrative Core (Core A) with four subdivisions, and four research cores (Cores B, C, D, and E). Core A (Administrative), provides overall leadership, management, and organizational support to the Center, operates the educational component (lectures and seminars), links users to biostatistical services (a research subdivision), assists with preparation of IRB materials, monitors issues of human research protection, and develops participant registries. Core B (Genetics) provides centralized tissue culture, amino acid/organic acid analyses, standard and molecular cytogenetics, specialized molecular genetics (DNA and RNA analyses) microarrarys and bioinformatics. Core C (Neuroscience) provides synaptic neurochemistry (focusing on histology imaging and high performance liquid chromatography) and lipid biochemistry (lipid metabolism, fatty acid analysis, and mass spectrometry services). Core D (Neuroimaging) provides for acquisition and quantitative analysis of data derived from functional, volumetic, diffusion tensor, and spectroscopic MR imaging. Core E (Behavior Science) offers training of subjects for cooperation with research protocols, selection and administration of standardized tests (developmental, cognitive, and functional), direct observations of behavior, design of activation paradigms for fMRI, and motion analysis (e.g., quantitative computer-assisted methods of documenting gaits, reaching, and learning behaviors within the motor domain). The core units serve 156 projects representing current direct annual NIH support totaling over $104 million dollars. The program addresses 30 of the 31 priority areas set forth in the RFA-HD-07-012, featuring interdisciplinary collaboration and a central theme, brain mechanisms whereby genotypes result in specific cognitive and behavioral phenotypes of mental retardation or developmental disability.