Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia

Am J Med Genet. 1996 Feb 16;67(1):63-70. doi: 10.1002/(SICI)1096-8628(19960216)67:1<63::AID-AJMG11>3.0.CO;2-N.


DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distribution of the Msp I and Bal I genotypes were not independent in 297 individuals (chi 2 = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism (chi 2 = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls (chi 2 = 5.3, df = 1, P = 0.02) and found more important in mal than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls (chi 2 = 0.06, df = 1, P = 0.80, chi 2 = 0.22, df = 1, P = 0.90 and chi 2 = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3' part of the gene may explain the discrepant results obtained with the two polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Deoxyribonuclease HpaII
  • Deoxyribonucleases, Type II Site-Specific
  • Genotype
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3
  • Schizophrenia / genetics*


  • DNA Primers
  • DRD3 protein, human
  • Drd3 protein, rat
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Deoxyribonuclease HpaII
  • Deoxyribonucleases, Type II Site-Specific
  • TGGCCA-specific type II deoxyribonucleases

Associated data

  • GENBANK/U25441