title: Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.
abstract: 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.
authors.affiliation: Unité de Neurobiologie et Pharmacologie, Centre Paul Broca l'INSERM, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Griffon
authors.forename: M A
authors.initials: MA
authors.lastname: Crocq
authors.forename: C
authors.initials: C
authors.lastname: Pilon
authors.forename: M P
authors.initials: MP
authors.lastname: Martres
authors.forename: A
authors.initials: A
authors.lastname: Mayerova
authors.forename: G
authors.initials: G
authors.lastname: Uyanik
authors.forename: E
authors.initials: E
authors.lastname: Burgert
authors.forename: F
authors.initials: F
authors.lastname: Duval
authors.forename: J P
authors.initials: JP
authors.lastname: Macher
authors.forename: F
authors.initials: F
authors.lastname: Javoy-Agid
authors.forename: C A
authors.initials: CA
authors.lastname: Tamminga
authors.forename: J C
authors.initials: JC
authors.lastname: Schwartz
authors.forename: P
authors.initials: P
authors.lastname: Sokoloff
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D017931:DNA Primers; C493593:DRD3 protein, human; C493595:Drd3 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; C060616:TGGCCA-specific type II deoxyribonucleases