Human dopaminergic neurons are involved in the control of hormone secretion, voluntary movement, and emotional behavior. Mediating these effects are the dopamine D1 and D2 receptors. These macromolecules belong to a large family of related sequences known as the G protein-coupled receptors. The D2 receptors have been of special interest because they bind, with high affinity and specificity, many of the commonly prescribed antipsychotic drugs. We previously isolated a full-length cDNA clone of the rat D2 receptor. When a chromosome mapping panel was probed with the rat D2 receptor cDNA a 15-kb EcoRI restriction fragment was identified and localized to human chromosome 11. The rat cDNA was also used to clone a human genomic fragment, lambda hD2G1, which contains the last coding exon of the D2 receptor gene (DRD2) and 16.5 kb of 3' flanking sequence. Hybridization of lambda hD2G1 to a chromosome 11 regional mapping panel localized DRD2 to 11q. In situ hybridization of lambda hD2G1 to metaphase chromosomes refined this assignment to the q22-q23 junction of chromosome 11. A search for RFLPs associated with D2DR identified a frequent two-allele TaqI RFLP.
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Arch Gen Psychiatry
July 1991
Neuropsychiatric Institute, UCLA 90024.
The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene.
View Article and Find Full Text PDFJAMA
December 1990
Section on Genetic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md 20892.
Using the dopamine D2 receptor clone lambda hD2G1, Blum et al recently found that the D2/Taq I allele (A1) was present in 69% of 35 deceased alcoholics but in only 20% of an equal number of controls. To assess this association further, we evaluated the D2/Taq I polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3' noncoding region of the D2 receptor gene. We studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees.
View Article and Find Full Text PDFJAMA
April 1990
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284.
In a blinded experiment, we report the first allelic association of the dopamine D2 receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3' coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3' sequence of the human dopamine D2 receptor gene (lambda hD2G1).
View Article and Find Full Text PDFHum Hered
June 1990
Department of Psychiatry, Washington University School of Medicine, St. Louis, Mo.
A genetic linkage study of fifteen families (n = 166) ascertained through probands diagnosed for Tourette syndrome was carried out for the D2-dopamine receptor and flanking loci on chromosome 11q22-q23. Tight linkage was excluded for all probes and regions of exclusion up to +/- 20% recombination were obtained. Overlapping regions of exclusion based upon primary map data permit exclusion of the entire region of the DRD2 locus in Tourette syndrome.
View Article and Find Full Text PDFAm J Hum Genet
November 1989
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, 97201.
Human dopaminergic neurons are involved in the control of hormone secretion, voluntary movement, and emotional behavior. Mediating these effects are the dopamine D1 and D2 receptors. These macromolecules belong to a large family of related sequences known as the G protein-coupled receptors.
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