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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene.

We have attempted to identify regions involved in the transcriptional regulation of the DAT1 (HUGO approved symbol SLC6A3) gene that may harbor functional variants predisposing to several neuropsychiatric disorders by examining haplotypes of various 5' and intronic regions for their effect on expression in a dopaminergic cell line. A 1.5-fold difference in regulatory activity was observed between haplotypes of the proximal promoter/intron 1 region, representing the two previously identified 5' clades. Although we found no effect on transcription with inclusion of the 9- and 10-repeat alleles of the 3' VNTR, introns 9, 12, and 14 appear to contain enhancer elements capable of increasing expression approximately 2-fold with respect to the promoter constructs. Differences in expression were also observed between two alleles of intron 14. These results thus suggest that it may be the particular combination of polymorphisms in a haplotype across the gene that ultimately affects DAT1 gene expression.[1]

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