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

Abstract

ABSTRACT. Polymorphisms of human genes encoding 5-hydroxytriptamine (serotonin) receptors (5-HTRs) are thought to be associated with psychiatric disorders and behavioral traits. In the present study, we searched for corresponding polymorphisms in the dog and compared allelic frequencies for the canine 5-HTR1B, 5-HTR2A, and 5-HTR2C genes among five canine breeds. The canine genes consisted of the following: 5-HTR1B, 1170 bp; 5-HTR2A, 1413 bp; and 5-HTR2C, 1377 bp. All of these genes were highly homologous with the human genes. We found six single nucleotide polymorphisms (SNPs) in the 5-HTR1B gene (G57A, A157C, G246A, C660G, T955C, and G1146C). Genotyping of the respective SNPs revealed that there were inter-breed variations in the genotypes and allelic fre quencies for four out of the six identified SNPs, suggesting that further analyses of the polymorphisms of the 5-HTR1B gene would be useful in order to gain an understanding of the genetic background underlying the diversified behavioral traits among canine species. KEY WORDS: behavior, breed difference, canine, 5-hydroxytriptamine receptor, polymorphism.J. Vet. Med. Sci. 66(8): 965-972, 2004 A number of studies have been recently conducted, particularly in the field of psychiatry, in the attempt to gain a better understanding of the genetic background of the human temperament [25]. However, as social, cultural, and environmental factors exert such profound effects on the development of human brain functions and on the personality in general, it remains extremely difficult to determine the causal relationships between genes and behavior. 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]. In rodents, 5-HTR1B knockout mice have been shown to display more reactive and less anxious behaviors than their wild-type counterparts [34], and they have also been shown to exhibit enhanced aggressive behavior [26]. As regards the 5-HT 2A receptor (5-HTR2A), even a silent mutation of T102C has been indicated as exerting ...

Canine Tyrosine Hydroxylase (TH) Gene and Dopamine .BETA.-Hydroxylase (DBH) Gene: Their Sequences, Genetic Polymorphisms, and Diversities among Five Different Dog Breeds

“…the 1 Mb resolution radiation hybrid map of the canine genome [10], the map of 4249 genetic markers featuring one marker every 900kb [3]. Therefore we have tried to search genetic markers that would be related to the behavioral traits in dogs and so far found some single nucleotide polymorphisms (SNPs) in neurotransmitter-related genes [12,19,20].…”

5-HTR2A and IL-6 polymorphisms and obstructive sleep apnea-hypopnea syndrome

“…Therefore, variables that affect serotoninergic activities can lead to sleep and breathing disorders. 5-HTR2A is an essential component of the serotoninergic system, mainly distributed at the hypoglossal motor neurons, and its expression is regulated by 5-HTR2A genes, located on chromosome 13q14-q21 (16). Therefore, polymorphisms in the 5-HTR2A gene can affect the number of receptors and contribute to OSAHS.…”

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

“…Dogs have been domesticated for over 15,000 years and the selective breeding for preferred and characteristic phenotypes has resulted in many breeds with specific characteristics in terms of appearance, skills and temperament, which are thought to reflect their genetic background. Therefore, dogs are regarded as good model for behavior genetic study [17,23], and it should be possible to identify canine temperament-associated genes by association analysis using candidate genes and genome-wide information as perfomed in human genetic studies [10,21].…”

“…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).…”