DOPAMINE TRANSPORTER-HUMAN & MOUSE GENES, DOPAMINERGIC DISORDERS & KNOCKO

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The rewarding/reinforcing effects of cocaine have been thought to be produced, at least in part, by blocking reuptake of dopamine by the dopamine transporter (DAT). This is the site that accumulates each of the dopamine selective toxins that produce the best current experimental models for Parkinson's disease. The DAT gene is expressed in dopaminergic neurons of the ventral midbrain, and serves as the only currently-available marker expressed almost exclusively by these cells. During this FY, we completed sequencing of the human DAT gene, characterized each of the polymorphisms in its coding and several intronic regions, and examined the distributions of these polymorphisms in populations with drug abuse, ADHD, Tourette's syndrome, and several other phenotypes. We also completed mapping the patterns of linkage disequilibrium accross this locus. No clear coding region disease-related protein variant was identified. However, continued strengthening of association between the 3' untranslated region VNTR marker and ADHD in several studies spurs interest in regulatory region polymorphisms at this interesting locus.