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Title: Dopamine D{sub 3} receptor gene: Organization transcript variants, and polymorphism associated with schizophrenia

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D{sub 3} 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 distributions of the Msp I and Bal I genotypes were not independent in 297 individuals ({chi}{sup 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}{sup 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}{sup 2}= 5.3, df = 1, P = 0.02) and found more important inmore » males 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}{sup 2}= 0.06, df = 1, P = 0.80, {chi}{sup 2} = 0.22, df = 1, P = 0.90 and {chi}{sup 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{prime} part of the gene may explain the discrepant results obtained with the two polymorphisms. 36 refs., 2 figs., 4 tabs.« less
Authors:
; ;  [1]
  1. Centre Paul Broca de l`INSERM, Paris (France) [and others
Publication Date:
OSTI Identifier:
437199
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Medical Genetics; Journal Volume: 67; Journal Issue: 1; Other Information: PBD: 16 Feb 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; MENTAL DISORDERS; NERVOUS SYSTEM DISEASES; GENOTYPE; DOPAMINE; RECEPTORS; TRANSCRIPTION; GENE MUTATIONS; STRUCTURE-ACTIVITY RELATIONSHIPS; SPLICING; GENETIC MAPPING; AGE DEPENDENCE; SEX DEPENDENCE; HUMAN CHROMOSOME 3; DNA SEQUENCING; POLYMERASE CHAIN REACTION; STATISTICS; RFLPS