A HYPERVARIABLE SEGMENT IN THE HUMAN DOPAMINE RECEPTOR D(4) (DRD4) GENE

The human dopamine D4 receptor contains a novel polymorphism within th e 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 re ceptor is the site through which the atypical neuroleptic clozapine ex erts its antipsychotic action and that some polymorphic variants displ ay different pharmacological properties. Further analysis of the repea t region using innovative technologies indicates that the alleles vary not only in the number of repeats (2-8 or 10 repeat units) but also i n the sequence of the repeats and the order in which they appear. In 1 78 unrelated chromosomes we have identified 19 different repeats in 25 different haplotypes coding for 18 different predicted amino acid seq uences, making this one of the most variable functional proteins curre ntly described.