title: The serotonin transporter intronic VNTR enhancer correlated with a predisposition to affective disorders has distinct regulatory elements within the domain based on the primary DNA sequence of the repeat unit.
abstract: We have demonstrated that a variable number tandem repeat domain (VNTR) within intron 2 of the serotonin transporter gene is a transcriptional regulatory domain which is potentially correlated with a predisposition to affective disorders and other behavioural conditions. This correlation based on copy number of the VNTR alone (nine, 10 or 12 copies of 16/17 base-pair element) has been controversial and not reproduced in all studies. We demonstrate that individual repeat elements within the VNTR domain differ in their enhancer activity in an embryonic stem cell model. This has implications for both the mechanism by which these VNTRs are correlated with the progression of the disease and suggests that clinical analysis should now be extended to correlate sequence variation within the VNTR with the disorder. The latter may resolve some of the conflicting data published to date.
authors.affiliation: Department of Veterinary Pathology, University of Edinburgh, EH9 1QH, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Lovejoy
authors.forename: A C
authors.initials: AC
authors.lastname: Scott
authors.forename: C E
authors.initials: CE
authors.lastname: Fiskerstrand
authors.forename: V J
authors.initials: VJ
authors.lastname: Bubb
authors.forename: J P
authors.initials: JP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002822:Choriocarcinoma; D004742:Enhancer Elements, Genetic; D018628:Gene Dosage; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D017930:Genes, Reporter / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors; D006801:Humans; D007438:Introns / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D051379:Mice; D018598:Minisatellite Repeats / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse