Transient expression analysis of allelic variants of a VNTR in the dopamine transporter gene (DAT1)

Jonathan Mill,Ian Craig,Philip Asherson,Ursula M D'Souza

doi:10.1186/1471-2156-6-3

Jonathan Mill, Ian Craig + Show 2 more

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https://doi.org/10.1186/1471-2156-6-3

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Journal: BMC Genetics	Publication Date: Jan 1, 2005
Citations: 126	License type: cc-by

Affiliation: Psychiatry Research Trust

Abstract

BackgroundThe 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT1) has been associated with a range of psychiatric phenotypes, most notably attention-deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study we have characterised the genomic structure of the 9- and 10-repeat VNTR alleles, and directly examined the role of the polymorphism in mediating gene expression by measuring comparative in vitro cellular expression using a reporter-gene assay system.ResultsDifferences in the sequence of the 9- and 10- repeat alleles were confirmed but no polymorphic differences were observed between individuals. There was no difference in expression of reporter gene constructs containing the two alleles.ConclusionsOur data suggests that this VNTR polymorphism may not have a direct effect on DAT1 expression and that the associations observed with psychiatric phenotypes may be mediated via linkage disequilibrium with other functional polymorphisms.

Highlights

The 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT1) has been associated with a range of psychiatric phenotypes, most notably attention-deficit hyperactivity disorder
Sequence analysis of the DAT1 VNTR Differences were found between repeat motifs, and nine variants were detected in total
Differences were found between the orders of motifs in 9- and 10-repeat alleles, they were identical for all examples of each allele size

Summary

Introduction

The 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT1) has been associated with a range of psychiatric phenotypes, most notably attention-deficit hyperactivity disorder. The mechanism for this association is not yet understood, several lines of evidence implicate variation in gene expression. Genetic association studies provide considerable evidence that a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes. Its location within the transcribed 3'-UTR is interesting since these regions have been shown to play an important role in the regulation of transcription efficiency, mRNA stability or mRNA sub-cellular localization [6]

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