A Novel A/G SNP in the -615th Position of the Dopamine D4 Receptor Promoter Region As A Source of Misgenotyping of the -616 C/G SNP

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The polymorphic 5′ upstream region of the dopamine D4 receptor (DRD4) gene containing several single nucleotide polymorphisms (SNPs) has recently become a focus of association studies in psychiatric genetics. Most SNP genotyping methods are based on the two-step procedure of restriction fragment length polymorphism (RFLP). An alternative technique is a single-step method of allele-specific amplification (ASA), previously introduced for genotyping the -521 C/T SNP of the DRD4 promoter region and applied here for the -616 C/G SNP. Parallel genotyping of individuals with the novel ASA method and the conventionally used Ava II RFLP showed a potential underestimation of the -616 GG genotype frequency by the conventional method. Sequencing the dubious samples clearly demonstrated a novel A/G SNP at the -615th position influencing the Ava II digestion and thus resulting in misgenotyping. To avoid this problem, we introduced the Sau96 I RFLP for the -616 C/G genotyping as this restriction enzyme is not sensitive for the -615 A/G sequence variation. Allele (-616 G = 0.48; -616 C = 0.52) and genotype (-616 GG = 0.25; -616 GC = 0.46; -616 CC = 0.29) frequencies were determined by both the novel ASA and the Sau96 I methods. The obtained genotype frequencies corresponded to the Hardy-Weinberg equilibrium in our healthy Caucasian sample (N = 534, P = 0.168). Using these methods, no association was found between the -616 C/G SNP and personality factors of Cloninger's temperament and character inventory (N = 153) in our population.

Original languageEnglish
Pages (from-to)74-78
Number of pages5
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume126 B
Issue number1
Publication statusPublished - Apr 1 2004



  • -615 A/G
  • -616 C/G
  • Allele-specific amplification
  • Association study
  • Dopamine D4 receptor (DRD4)
  • Personality
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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