Sequence Comparison of the Dopamine Receptor D4 Exon III Repetitive Region in Several Species of the Order Carnivora.

Inoue‐Murayama, Miho; Matsuura, N.; Murayama, Yuichi; Tsubota, Toshio; Iwasaki, Tadaaki; Kitagawa, Hitoshi; S, Itó

doi:10.1292/jvms.64.747

Cited by 12 publications

(8 citation statements)

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“…This characteristic caused low heterozygosity in Shibas. A similar phenomenon was seen in the canine DRD4 polymorphic regions [9,15,16]. Since the primary difference between the Shiba and the other breeds is its origin, i.e., the Shiba is Japanese in origin whereas the others are European, this finding might reflect the regional diversity thought to exist in humans [4].…”

Section: Discussionsupporting

confidence: 60%

“…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].…”

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confidence: 80%

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

Masuda

Hashizume

Kikusui

et al. 2004

The Journal of Veterinary Medical Science

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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...

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Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 80%

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

Masuda

Hashizume

Kikusui

et al. 2004

The Journal of Veterinary Medical Science

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“…Moreover, we also found, among species in Carnivora, only Canidae (dog, wolf, and raccoon dog) had repeat structure and/or polymorphism in exon III of DRD4 [10], indicating that this polymorphism is not widely spread in Carnivora.…”

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confidence: 72%

Allele Frequency Distribution of the Canine Dopamine Receptor D4 Gene Exon III and I in 23 Breeds

Itô

Nara

Inoue‐Murayama

et al. 2004

The Journal of Veterinary Medical Science

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ABSTRACT. Various canine breeds are remarkably different from each other not only in their sizes and shapes but also in behavioral traits, suggesting that some of them are under genetic control. Although dopaminergic neurotransmission system is considered to affect animal behavior, little is known about related genes in canine. Relations between specific alleles in polymorphic regions of the dopamine receptor D4 gene (DRD4) and personality or psychiatric disorders have been reported in humans, and we first found polymorphism in exon III region of the gene in 4 canine breeds. In this study we surveyed allele frequency distribution in 23 breeds including a total of 1,535 unrelated individuals. In exon III, 8 alleles including a novel allele were identified. A group of breeds in which the alleles 447b, 498 and 549 were frequent tended toward high scores in aggression-related behavioral traits than that with frequent alleles 435 and 447a. Moreover, a polymorphism based on 24 bp insertion/deletion was found in exon I region for the first time in dogs. This information may be of use for candidate gene studies of behavioral variation in dogs. KEY WORDS: canine, dopamine receptor D4 gene, exons III and I, polymorphism, variation among breeds.J. Vet. Med. Sci. 66 (7): [815][816][817][818][819][820] 2004 The dog (Canis familiaris) is one of the oldest domestic species [6]. Repeated selection for the various purposes, such as hunting, herding and guarding, has made dogs vary in size, shape and behavior. Consequently, more than 400 canine breeds currently exist, and behavioral traits as well as external morphology are different among breeds [2,9,19], suggesting that some of them are under genetic control.In humans, several candidate genes have been reported to have association between their polymorphisms and particular personality [1,8,12,17]. Dopamine receptor D4 gene (DRD4), which is one of the genes relevant to neurotransmitters, includes polymorphisms in several regions. Associations have been reported between these polymorphisms and personality or psychiatric disorders, such as 'Novelty Seeking' [1], attention deficit hyperactivity disorder (ADHD) [11] and delusional disorder [4], although a considerable number of reports found no association [3,21]. The association between DRD4 and 'Novelty Seeking' is further supported by the study that DRD4 knock-out (DRD4-/-) mice are significantly less behaviorally responsive to novelty than are DRD4+/+ wild-type mice [7], suggesting that this association may be applied to other mammalian species.We previously investigated exon III region of DRD4 in dogs, demonstrated polymorphism as observed in humans, identified 7 alleles (396, 435, 447a, 447b, 486, 498 and 549) based on the number and order of the 12 and 39 bp units, and found that allele frequencies significantly varied among 4 breeds (Beagle, Golden Retriever, Shetland Sheepdog and Shiba) [14,15]. Moreover, we also found, among species in Carnivora, only Canidae (dog, wolf, and raccoon dog) had repeat structure and/or po...

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“…[142][143][144][145] Twentythree dog breed were studied for aggression, and association was observed between this trait and the exon III polymorphism. 142 In the genus Equus (horses), the DRD4 exon III region includes an 18-bp repeat unit and there are inter-and intra-species differences in the number of repetitions.…”

Section: Gene-environment Interactionsmentioning

confidence: 99%

The molecular genetic architecture of human personality: beyond self-report questionnaires

2006

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Molecular genetic studies of personality began with two high impact papers in 1996 that showed provisional associations between the dopamine DRD4 exon III repeat region and Novelty Seeking/Extraversion. These first two reports were shortly followed by an investigation linking Neuroticism/Harm Avoidance with the serotonin transporter (SLC6A4) promoter region polymorphism (5-HTTLPR). In the ensuing decade, thousands of subjects have been studied for association between these genes and personality, assessed by using self-report questionnaires, with erratic success in replication of the first findings for Novelty Seeking (DRD4) and Harm Avoidance (5-HTTLPR). Small effect sizes characteristic of non-Mendelian traits, polygenic patterns of inheritance and true heterogeneity between studies confound attempts to reach a consensus regarding the role of common polymorphisms in contributing to personality domains. Nevertheless, the current state of personality genetics is far from being bleak. Several new paradigms especially functional neuroimaging or 'imaging genomics' have strengthened the connection between 5-HTTLPR and anxiety-related personality traits. The demonstrations that early environmental information can considerably strengthen and even uncover associations between genes and behavior (Caspi's seminal studies and more recently the demonstration that early environment impacts on DRD4 and Novelty Seeking) are notable and herald a new era of personality genetics. Finally, consideration of the broader phenotypic expression of common polymorphisms (e.g. the 'social brain', altruism, etc.) and the use of new experimental paradigms including neurophysiological, neuropsychological and computer games that go beyond the narrow self-report questionnaire design will enable a deeper understanding of how common genetic polymorphisms modulate human behavior. Human personality, defined by Webster as the quality or state of being a person or the complex of characteristics that distinguishes an individual, surely requires a more encompassing view towards understanding its complex molecular genetic architecture.

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Sequence Comparison of the Dopamine Receptor D4 Exon III Repetitive Region in Several Species of the Order Carnivora.

Cited by 12 publications

References 14 publications

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

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

Allele Frequency Distribution of the Canine Dopamine Receptor D4 Gene Exon III and I in 23 Breeds

The molecular genetic architecture of human personality: beyond self-report questionnaires

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