© 1993 Oxford University Press
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A hypervariable segment in the human dopamine receptor D4 (DRD4) gene
The Du Pont Merck Pharmaceutical Company, Experimental Station PO Box 80328, Wilmington, DE 19880-0328 1Yale University, School of Medicine, Department of Genetics New Haven, CT 06510, USA 2The Clarke Institute of Psychiatry, Laboratory of Neurogenetics and Neurobiology, University of Toronto, Section of Neurogenetics Toronto, Ontario M5T 1R8, Canada
* To whom correspondence should be addressed
Received December 24, 1992; Revised March 19, 1993; Accepted March 19, 1993
The human dopamine D4 receptor contains a novel polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of direct imperfect 48-bp repeats in the gene. Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. Further analysis of the repeat region using innovative technologies indicates that the alleles vary not only in the number of repeats (2–8 or 10 repeat units) but also in the sequence of the repeats and the order in which they appear. In 178 unrelated chromosomes we have identified 19 different repeats in 25 different haplotypes coding for 18 different predicted amino acid sequences, making this one of the most variable functional proteins currently described.
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