Open AccessMolecular and behavioral analysis of the intron 2 repeat polymorphism in the canine dopamine D4 receptor gene
Author(s) -
Hejjas K.,
Kubinyi E.,
Ronai Z.,
Szekely A.,
Vas J.,
Miklósi Á,
SasvariSzekely M.,
Kereszturi E.
Publication year - 2009
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2008.00475.x
Subject(s) - exon , genetics , variable number tandem repeat , intron , gene , biology , allele , tandem repeat , impulsivity , polymorphism (computer science) , microbiology and biotechnology , medicine , genome , psychiatry
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.