Molecular and behavioral analysis of the intron 2 repeat polymorphism in the canine dopamine D4 receptor gene.
Genetic polymorphisms in the human dopamine D4 receptor (DRD4) gene, especially the exon 3 variable number of tandem repeats (VNTR), have been related to several psychiatric disorders and personality traits. A homologous exon 3 VNTR has been described in dogs, and we previously showed an association between the DRD4 exon 3 polymorphism and activity/impulsivity trait in German shepherds. In this study, we present a detailed analysis of the intron 2 VNTR of the DRD4 gene. A short and a long form of the intronic variation were identified in 678 unrelated dogs from five breeds and in 22 wolves. For molecular analysis, the intron 2 region was cloned into a promoterless luciferase reporter vector that led to an elevation in transcriptional activity. Moreover, an allelic difference in promoter activity was detected, and a repressive effect of the long allele was observed. Behavioral analysis of 96 unrelated German shepherds showed a significant association between the social impulsivity endophenotype of the Greeting Test and both the exonic (P = 0.002) and the intronic (P = 0.003) VNTRs of the DRD4 gene. Moreover, an additive effect of the two polymorphisms was also shown (Spearman's rho = 0.356, P = 0.0004). In conclusion, these results give further support to our previous findings that the DRD4 gene is associated with dog behavior. We also present molecular evidence for the functional role of the intron 2 VNTR in the canine DRD4 gene.
Hejjas
K
K
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Kubinyi
E
E
Ronai
Z
Z
Szekely
A
A
Vas
J
J
Miklósi
A
A
Sasvari-Szekely
M
M
Kereszturi
E
E
D000483:Alleles; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D004285:Dogs / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D007175:Impulsive Behavior / Q000235:genetics; D007438:Introns / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019655:Quantitative Trait, Heritable; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D019596:Wolves
D050638:Receptors, Dopamine D4; D004298:Dopamine