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Journal of Heredity Advance Access originally published online on October 26, 2005
Journal of Heredity 2005 96(7):786-796; doi:10.1093/jhered/esi108
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© The American Genetic Association. 2005. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Structure and Variation of Three Canine Genes Involved in Serotonin Binding and Transport: The Serotonin Receptor 1A Gene (htr1A), Serotonin Receptor 2A Gene (htr2A), and Serotonin Transporter Gene (slc6A4)

L. van den Berg, L. Kwant, M. S. Hestand, B. A. van Oost, and P. A. J. Leegwater

From the Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 8, 3584 CM Utrecht, Netherlands (van den Berg, Kwant, Hestand, and Leegwater); and the Department of Animals, Science and Society, Faculty of Veterinary Medicine, Utrecht University, Postbus 80166, 3508 TD Utrecht, Netherlands (van Oost)

Address correspondence to Linda van den Berg at the address above, or e-mail: L.vandenBerg{at}vet.uu.nl.

Aggressive behavior is the most frequently encountered behavioral problem in dogs. Abnormalities in brain serotonin metabolism have been described in aggressive dogs. We studied canine serotonergic genes to investigate genetic factors underlying canine aggression. Here, we describe the characterization of three genes of the canine serotonergic system: the serotonin receptor 1A and 2A gene (htr1A and htr2A) and the serotonin transporter gene (slc6A4). We isolated canine bacterial artificial chromosome clones containing these genes and designed oligonucleotides for genomic sequencing of coding regions and intron-exon boundaries. Golden retrievers were analyzed for DNA sequence variations. We found two nonsynonymous single nucleotide polymorphisms (SNPs) in the coding sequence of htr1A; one SNP close to a splice site in htr2A; and two SNPs in slc6A4, one in the coding sequence and one close to a splice site. In addition, we identified a polymorphic microsatellite marker for each gene. Htr1A is a strong candidate for involvement in the domestication of the dog. We genotyped the htr1A SNPs in 41 dogs of seven breeds with diverse behavioral characteristics. At least three SNP haplotypes were found. Our results do not support involvement of the gene in domestication.


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