The goal of the Molecular Core are to consolidate a range of molecular biological and molecular genetic methods that are required for several of the CTNA projects and pilot studies. The rationale for this core is both scientific and practical. From the scientific perspective, it makes sense to place these methodologies under a single entity to ensure that state-of- the-art techniques and approaches are used. For example, the Core will ensure that genotyping strategies used for clinical samples and for transgenic mice both take advantage of the most accurate and high throughput approaches available, not only now but also over the five year course of the grant. From the practical perspective, pacing these technologies within a single Core increases efficiencies and economy of scale, thereby deriving considerable savings for the overall CTNA. With Dr. Nestler serving as Director of the Core and Dr. Gelernter serving as Co-Director, the Core provides a concrete vehicle of interaction between genetic studies in mice and humans that are supported by the CTNA. Thus, the Core bolsters the translational nature of the proposed studies, which is a major defining feature of the CTNA proposal. 1. Animal genetic studies: To breed and genotype several lines of inducible, tissue-specific transgenic mice that support the expression of transcription within brain regions of interest. 2. Human genetic studies: To type closely-spaced short tandem repeat (STR) markers in regions identified in previous genome studies (COGA, NIAAA) as potentially linked to alcohol dependence, and to then screen for mutations that potentially affect the function of candidate genes that map to linkage disequilibrium regions.
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