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Related Experiment Videos

A hypervariable segment in the human dopamine receptor D4 (DRD4) gene

J B Lichter1, C L Barr, J L Kennedy

  • 1Du Pont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0328.

Human Molecular Genetics
|June 1, 1993
PubMed
Summary
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The human dopamine D4 receptor gene has a novel polymorphism with varying numbers and sequences of DNA repeats. This genetic variation influences receptor properties and may affect responses to antipsychotic drugs like clozapine.

Area of Science:

  • Neuroscience
  • Human Genetics
  • Pharmacology

Background:

  • The dopamine D4 receptor is a target for atypical antipsychotic drugs.
  • A polymorphism in the third cytoplasmic loop of the dopamine D4 receptor has been identified.

Purpose of the Study:

  • To characterize the novel polymorphism in the human dopamine D4 receptor gene.
  • To investigate the variability in repeat number, sequence, and order within the polymorphism.
  • To explore the potential impact of these variations on receptor function and drug response.

Main Methods:

  • Analysis of the repeat region using innovative technologies.
  • Identification and sequencing of different alleles and haplotypes.
  • Genotyping of 178 unrelated chromosomes.

Related Experiment Videos

Main Results:

  • The polymorphism involves variable numbers (2-10) of imperfect 48-bp repeats.
  • Alleles differ in repeat number, sequence, and order.
  • 19 different repeats, 25 haplotypes, and 18 predicted amino acid sequences were identified.
  • This represents one of the most variable functional proteins described.

Conclusions:

  • The dopamine D4 receptor exhibits extensive genetic variability due to a complex repeat polymorphism.
  • This variability may underlie differences in pharmacological properties and clinical responses to drugs like clozapine.
  • Further research is warranted to elucidate the functional and clinical implications of this high degree of genetic diversity.