The human dopamine transporter (DAT, SLC6A3) has been extensively investigated because of its potential involvement in neuropsychiatric disorders. The core elements responsible for its transcription have been identified. A regulatory role for certain genomic variants upstream to the core promoter is known. Recently, other single-nucleotide polymorphisms (SNPs) have been identified in this region and are thought to be associated with schizophrenia and bipolar I disorder. Hence, we have investigated the impact of common SNPs in a 2.8-kilobase region flanking the core promoter region (-2.7 to +63 base pair) in the neuroblastoma cell line SH-SY5Y. Haplotypes generated by site-directed mutagenesis revealed varying impact of individual SNPs on promoter activity using dual luciferase assays. In silico analyses also predicted allele-specific binding of transcription factors for some of these SNPs. Though electrophoretic mobility shift assays indicated several factors that appeared to bind to specific sites within this region, allele-specific binding was not detected for any SNP apart from rs3756450. We have thus identified novel putative regulatory domains flanking the core promoter of DAT that merit further investigation. © The Author 2009.
CITATION STYLE
Bamne, M. N., Talkowski, M. E., Chowdari, K. V., & Nimgaonkar, V. L. (2010). Functional analysis of upstream common polymorphisms of the dopamine transporter gene. Schizophrenia Bulletin, 36(5), 977–982. https://doi.org/10.1093/schbul/sbp005
Mendeley helps you to discover research relevant for your work.