Breed Differences in Genotype and Allele Frequency of Catechol O-Methyltransferase Gene polymorphic Regions in Dogs

Abstract

ABSTRACT. Catechol O-methyltransferase (COMT) inactivates catecholamines and catechol-containing drugs such as L-DOPA. The common genetic polymorphism Val158Met in the human COMT gene is suspected to be associated with "persistence" or risk for schizophrenia. In this study, we attempted to identify the canine COMT gene fragment and to find a similar polymorphism and to reveal its genetic distribution among five representative canine breeds. We found that the amplified gene consisted of 663 bp nucleotides and was 84% homologous with the human COMT gene. The single nucleotide polymorphisms, guanine adenine substitution, were observed at the 39th, 216th and 482nd nucleotides. From the genotyping of the 216th polymorphism among 266 dogs by the polymerase chain reaction-restriction fragment length polymorphism method with restriction enzyme EagI, and that of the 482nd polymorphism with restriction enzyme SfcI, we found inter-breed variations of genotypes as well as of allelic frequencies for both of these polymorphic region s. These results suggest that the identified polymorphisms will be useful tools in elucidating the genetic background of canine behavioral traits. KEY WORDS: amino acid substitution, breed difference, canine, catechol O-methyltransferase gene, restriction fragment length polymorphism.J. Vet. Med. Sci. 66(2): 183-187, 2004 The dog (Canis familiaris) has a long and close association with humans, and as a result of selected breeding for various purposes such as hunting and working, there are numerous canine breeds. Dogs vary not only in shape and size but also in behavioral characteristics according to breed. Hart and Hart conducted a survey in which they compared behavioral characteristics among breeds and found that breeds used as guard dogs were strongly characterized by the behavioral traits of territorial defense and watchdog barking, whereas household dogs showed little aggressiveness and were highly responsive to obedience training [7].In recent years research into the genetic basis of temperament in human beings has drawn a great deal of attention. The genetic polymorphism of the dopamine D4 receptor (DRD4) was reported to be related to the temperament of "novelty-seeking," and that of the promoter region of serotonin transporter was reported to be related to "harm-avoidance" in human studies [2,5,12]. Extrapolating the DRD4 results in order to investigate the same topic in dogs, researchers found, in accordance with specific behavioral traits, a breed difference in the genomic polymorphism of the domain that is similar to that studied in humans [9,15,16].Catechol O-methyltransferase (COMT) inactivates catecholamines and catechol-containing drugs such as L-DOPA. The common genetic polymorphism Val158Met in the human COMT gene is suspected to be associated with "persistence" or risk for schizophrenia in human studies [3]. In order to determine whether there is a similar polymorphism in dogs that is related to canine behavioral traits, we identified the canine COMT gene and analyzed its gene...

Sequencing of Canine 5-Hydroxytriptamine Receptor (5-HTR) 1B, 2A, 2C Genes and Identification of Polymorphisms in the 5-HTR1B Gene

“…For the analysis of the genomic distributions of identified polymorphisms, peripheral blood samples were obtained from 189 individuals (46 Golden retrievers, 40 Labrador retrievers, 40 Malteses, 26 Miniature schnauzers, 37 Shiba Inu) via 11 cooperative veterinary hospitals in the Kansai, Kanto, and Chu-bu areas in Japan [17]. Genomic DNA was extracted with the QIAamp Blood Kit (Qiagen, U.S.A.).…”

“…Companion animals such as dogs, which have a much simpler social system than human beings, but whose rich individuality can nonetheless be described objectively, have been considered as an advantageous object for this type of research that investigates the genetic components of behavioral traits. We therefore undertook an analysis of the genetic background of the canine temperament in order to create a list of polymorphic regions that might serve as possible candidates for influencing the canine temperament; in this context, we have thus far reported the single nucleotide polymorphisms (SNPs) in the cathechol o-methyltransferase gene [17].Serotonin (5-hydroxytriptamine: 5-HT) is an important monoaminergic neurotransmitter, and it is thought to play a considerable role in psychiatric disorders such as depression, anxiety, and substance abuse; the polymorphisms of certain 5-HT receptor genes are suspected to be involved in these disorders. Among the 5-HT receptors, the 5-HT 1B receptor (5-HTR1B) is assumed to be associated with antisocial alcoholism [14] and antisocial substance dependencies in humans [13].…”

“…Companion animals such as dogs, which have a much simpler social system than human beings, but whose rich individuality can nonetheless be described objectively, have been considered as an advantageous object for this type of research that investigates the genetic components of behavioral traits. We therefore undertook an analysis of the genetic background of the canine temperament in order to create a list of polymorphic regions that might serve as possible candidates for influencing the canine temperament; in this context, we have thus far reported the single nucleotide polymorphisms (SNPs) in the cathechol o-methyltransferase gene [17].…”

Sequences and Polymorphisms of the Canine Monoamine Transporter Genes SLC6A2, SLC6A3, and SLC6A4 among Five Dog Breeds

“…The full lengths of the coding regions of the canine SLC6A2, SLC6A3, and SLC6A4 genes were sequenced using consensus primers designed from registered sequences of other species [GenBank accession numbers SLC6A2: NM_001043 (human), NM_009209 (mouse), SLC6A3: NM_001044 (human), NM_010020 (mouse), SLC6A4: NM_001045 (human), NM_010484 (mouse)] and complementary DNA (cDNA) obtained by reverse-transcription of brain mRNA from a Beagle, as described previously [6,[14][15][16]22]. This resulted in the determination of nucleotide sequences with open reading frames of 1854 bp (SLC6A2), 1854 bp (SLC6A3), and 1893 bp (SLC6A4).…”

“…Based on this concept, we examined the genetic variation of the identified polymorphisms among dog breeds as follows. We used 190 samples of peripheral blood as our previous studies [6,[14][15][16]22]. These were obtained from five different dog breeds selected for their popularity in Japan and breed-specific temperament traits [24] (Golden Retriever, n=46; Labrador Retriever, n=41; Maltese, n=40; Miniature Schnauzer, n=25; and Shiba, n=38).…”