Systematic screening for mutations in the 5'-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder

Am J Med Genet. 1996 Jul 26;67(4):424-8. doi: 10.1002/(SICI)1096-8628(19960726)67:4<424::AID-AJMG21>3.0.CO;2-K.


A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5'-flanking region of the dopamine D1 receptor (DRD1) gene. This region has previously been shown to contain a functional promoter [Minowa et al., 1992: Proc Natl Acad Sci 89:3045-3049; Minowa et al., 1993: J Biol Chem 268:23544-23551]. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations was found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5'-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Bipolar Disorder / genetics*
  • DNA Primers
  • Gene Frequency
  • Humans
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Dopamine D1 / genetics*
  • Reference Values
  • Regulatory Sequences, Nucleic Acid*
  • Restriction Mapping
  • Schizophrenia / genetics*


  • DNA Primers
  • Receptors, Dopamine D1