title: Functional effects of a tandem duplication polymorphism in the 5'flanking region of the DRD4 gene.
abstract: BACKGROUND
  Several polymorphisms have been identified in the 5'flanking region of the human dopamine D(4) receptor gene (DRD4), including a tandem duplication polymorphism. This comprises a 120-base-pair repeat sequence that is known to have different allele frequencies in various populations around the world. Furthermore, various studies have revealed evidence of linkage to attention-deficit/hyperactivity disorder and association with schizophrenia and methamphetamine abuse. The location of the polymorphism in the 5'regulatory region of the DRD4 gene and the fact that it consists of potential transcription factor binding sites suggest that it might confer differential transcriptional activity of the alleles.
  
  
  METHODS
  We investigated the functional effects of this gene variant with transient transfection methods in four human cell lines and then assessed transcriptional activity with luciferase reporter gene assays.
  
  
  RESULTS
  The longer allele has lower transcriptional activity than the shorter allele in SK-N-MC, SH-SY5Y, HEK293, and HeLa cell lines.
  
  
  CONCLUSIONS
  This evidence suggests that the duplication might have a role in regulating the expression of the DRD4 gene and provides an understanding of the biological mechanisms underlying the etiology of neuropsychiatric disorders such as ADHD, schizophrenia, and metamphetamine abuse.
authors.affiliation: Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, Box Number P082, Denmark Hill, London SE5 8AF, United Kingdom. spjgumd@iop.kcl.ac.uk
authors.forename: Ursula M
authors.initials: UM
authors.lastname: D'Souza
authors.forename: Carsten
authors.initials: C
authors.lastname: Russ
authors.forename: Eda
authors.initials: E
authors.lastname: Tahir
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Asherson
authors.forename: Ian W
authors.initials: IW
authors.lastname: Craig
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D002460:Cell Line; D005091:Exons; D005456:Fluorescent Dyes / Q000378:metabolism; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020080:Tandem Repeat Sequences / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: C493599:DRD4 protein, human; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4