title: A hypervariable segment in the human dopamine receptor D4 (DRD4) gene.
abstract: 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.
authors.affiliation: Du Pont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0328.
authors.forename: J B
authors.initials: JB
authors.lastname: Lichter
authors.forename: C L
authors.initials: CL
authors.lastname: Barr
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: H H
authors.initials: HH
authors.lastname: Van Tol
authors.forename: K K
authors.initials: KK
authors.lastname: Kidd
authors.forename: K J
authors.initials: KJ
authors.lastname: Livak
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003024:Clozapine / Q000378:metabolism / Q000494:pharmacology; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D005796:Genes; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: C493599:DRD4 protein, human; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D003024:Clozapine