Allele frequency distribution of the canine dopamine receptor D4 gene exon III and I in 23 breeds

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.     

Breed Differences in Dopamine Receptor D4 Gene (DRD4) in Horses

Genetic polymorphisms in genes related to neurotransmitters or hormones affect personality or behavioral traits in many animal species including humans. In domestic animals, the allele frequency of such genes has been reported to be different among breeds and it may account for breed differences in behavior. In this study, we investigated breed differences in horses in the dopamine receptor D4 gene (DRD4), which has been reported to affect horse personality. We collected samples from seven horse breeds including those native to Japan and Korea, and compared the sequence of the DRD4 exon3 region among these breeds. We found that there were two types of polymorphisms (VNTR and SNPs) in the exon3 region, and some of them seemed to be breed-specific. In addition, we found that the allele frequency of G292A, reported to be associated with horse personality, differed greatly between native Japanese horses and Thoroughbred horses. The frequency of the A allele which is associated with low curiosity and high vigilance, was much lower in native Japanese horses (Hokkaido, 0.03; Taishu, 0.08) than in Thoroughbreds (0.62). This difference may account for breed differences in personality or behavioral traits. Further studies of the function of these polymorphisms and their effect on behavior are indicated.     

Identifying novel polymorphisms in the canine tryptophan hydroxylase 2 gene

Tryptophan hydroxylase (TPH) serves as the rate-limiting enzyme in the biosynthesis of serotonin, and two forms of TPH genes, TPH1 and TPH2, have been reported with specific nucleotide sequences and expression patterns. We determined the sequences of these two genes and identified polymorphisms within their coding regions. We identified five novel single nucleotide polymorphisms in the TPH2 gene, one of which resulted in a non-synonymous mutation and the remaining four in synonymous mutations. Comparison of the genotype frequencies of the polymorphisms among five popular breeds with different behavioral traits revealed statistically significant interbreed differences for three polymorphisms. These results suggest that these polymorphisms would be useful genetic markers when performing behavior studies in dogs.     

Progress of genome wide association study in domestic animals

ABSTRACT: Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described.     

First Report on the Occurrence of ‘Helicobacter heilmannii’ in the Stomach of Rabbits

Gastric Helicobacter spp. have been described in a wide range of animal species, including dogs, cats, primates, swine, cattle and rodents. However, in lagomorphs--more specifically rabbits--gastric Helicobacter infections have never been reported. Biopsy specimens were collected from different stomach regions of 23 rabbits, including 10 pet rabbits, 10 industrial animals and 3 research animals. These were subjected to a PCR assay for the detection of Helicobacter DNA. Identification up to the species level was based on 16S rRNA sequence analysis and a recently developed multiplex PCR. Seven rabbits (four pet, one research animal and two industrial animals) tested positive in the Helicobacter genus-specific PCR in the stomach, with the corpus being predominantly positive. H. felis and H. salomonis, hitherto presumed to be naturally hosted by cats and dogs, were detected in three animals and one animal, respectively. One of these animals had been completely devoid of any form of contact with cats or dogs. A H. pullorum/H. rappini-like organism (96% 16S rDNA sequence similarity) was found in an industrially held rabbit. The helicobacters of the two remaining rabbits could not be identified up to the species level. To conclude, this is the first report on the occurrence of Helicobacter spp. in the stomach of rabbits. In view of the fact that H. felis and H. salomonis are put forward as having zoonotic potential, further research is necessary to investigate the implications of these findings not only for the rabbit but also for human health.     

Morphology, immunohistochemistry, and genetic alterations in dog astrocytomas

Astrocytoma is one of the most common tumors of the central nervous system in animals. Of the domesticated animal species, most examples are seen in dogs, and the spectrum that has been described is quiet broad. Previous studies have revealed morphologic similarities between human and animal astrocytomas. Human astrocytomas are often associated with genetic alterations that determine the clinical behavior and therapy outcome. The purpose of this study was to further characterize astrocytomas in dogs and to determine whether there are genetic changes similar to those in the human counterpart.     

Behavioral problems of geriatric dogs and cats

Dogs and cats that have been perfectly acceptable pets for many years may develop behavioral problems with old age. Most often these problems develop in animals that have never been very well behaved but have been tolerated by the owners until the problem has somehow exacerbated secondary to some other geriatric problem. The behavioral problems of old dogs most likely to be encountered by the practitioner are those of deaf dogs, dogs that house-soil because of renal, cardiovascular or gastrointestinal problems, and dogs that are aggressive because of a change in the number of animals or humans in the household or that are aggressive secondary to a chronic painful condition such as arthritis. Common feline problems may concern changes in the cat's environment. The treatment of behavioral problems of old animals is similar to the treatment of the problems of young animals, except that the physical limitations and disabilities of the old, usually ill, animal must be considered. Owners should be advised of the behavioral problems that may occur secondary to degenerative diseases and also be persuaded to keep social and environmental changes to a minimum in an old animal's life.     

犬体型大小相关基因的研究进展

犬作为人类最早驯化的家养动物,在人类发展史和现代生活中扮演着非常重要的角色,如伴侣、看护、导盲、军警用犬等。人工选择过程使得家犬产生了极大的表型多样性,其中体型性状是犬最显著的表型性状之一,属高遗传力性状。本文综述了犬体型性状相关基因IGF1、IGF1R、GHR1、GHR2、SMAD2、STC2、HMGA2、IGSF1、ACSL4及IRS4的研究进展,为未来工作犬体型遗传改良育种提供重要的靶点和依据,为进一步阐明人类及其他家养动物在体型上的遗传变异提供参考。     

Behavioral characteristics of English Cocker Spaniels with owner-defined aggressive behavior

Information on the behavior of both aggressive and nonaggressive (control) English cocker spaniels (ECS) recruited for genetic analysis is presented. Information from a total of 122 dogs was gathered using questionnaires and owner interviews, resulting in analysis of 52 aggressive (5 aggressive dogs were excluded from the analysis) and 65 control dogs. Owners rated their dogs with 5-point frequency scales for unacceptable behavior toward humans (17 items), fear (20 items), barking (8 items), and aggression toward other dogs (4 items). The results show that serious, repeated growling is the most pronounced single behavior characterizing the aggressive ECS, and this seems to be the most important behavior causing owners to classify their dogs as aggressive. The other main behavior characteristic of the aggressive group was skin-penetrating bites. Snapping and “biting in general” were also frequently reported among these dogs. The objective of this study was to describe some behavioral characteristics of ECS showing owner-defined aggressive behavior, and behavioral differences between these dogs and a group of ECS with excellent behavior.     

Genetics and disease resistance

Genetic components of disease resistance have been described in most of important diseases in human as well as in laboratory and livestock animals. However the basic mechanisms have been established in a few examples only. The reasons herefore are the mostly polygenic inheritance of disease resistance traits, the missing of suitable animal models and the dominance of environmental effects like infection pressure, immune status, and stressors, limiting the view on responsible gene variants. Ethical and practical aspects may further hinder research on disease resistance in certain species. Livestock animals play a crucial role in disease resistance research, because of distinct genetic diversity within and between breeds, because of an often distinct metabolic congruency with humans, and aiming towards the improvement of hygiene and economy of production and animal welfare. The following sections will review disease resistance in livestock animals and their practical implications, completed by examples of our own research activities.     

Sequences of canine glutamate decarboxylase (GAD) 1 and GAD2 genes, and variation of their genetic polymorphisms among five dog breeds

Glutamate decarboxylase (GAD) is the primary enzyme in the brain that catalyzes the synthesis of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter. There are two isoforms named according to their molecular weights, GAD67 and GAD65, which are encoded by GAD1 and GAD2, respectively. To investigate the association between GAD genes and temperament in domestic dogs, Canis familiaris, we sequenced the full lengths of the coding regions of these genes and identified three single nucleotide polymorphisms (SNPs) in GAD1 and one in GAD2. When comparing genotype and allele frequencies of SNPs among five breeds with different behavioral traits, statistically significant interbreed differences were observed for three SNPs in GAD1. These results suggest that GAD1 SNPs may be useful for behavioral genetic studies in dogs.     

Comparative Genomics Approach to Identify Candidate Genetic Loci for Male Fertility

The article presents multi‐species, genome‐wide, comparative approach to review male fertility‐associated loci to contribute to the development of new genetic markers that could be of interest for functional studies and have the potential to be implemented in farm animal breeding programmes. We reviewed 835 male fertility‐associated candidate loci from seven species and presented them as bovine orthologues where possible. The candidate loci were identified exploiting seven different research approaches: (i) data from animal models: mouse transgenics and knock‐outs (569 genes) and random chemical mutagenesis of mouse genome (31); (ii) animal QTL (69); (iii) genes differentially expressed between fertile and subfertile phenotype in humans and mouse (95); (iv) DNA sequence variations that show specific allele‐phenotype interactions (43 in human and 13 in farm animals); (v) germ line‐specific small non‐coding RNAs (47); (vi) testes expressed genes controlling complex differentiation process of mammalian spermatogenesis (6); and (vii) epigenetically regulated genes (4). According to the number of different research approaches reporting effects of individual genes, we selected 33 most promising candidate genes, which were further in silico analysed for expression levels in testes, genetic variability and top biological functions in functional networks. The aim of this study was to review systematically male fertility‐associated candidate loci using integrated information from different study approaches and species, which will further facilitate development of novel genetic markers for selection towards improved fertility in domestic animals.     

Molecular genetics of behaviour: research strategies and perspectives for animal production

Genetic factors are undoubtedly involved in inter-individual variability of the behaviours that may be important for livestock production, as shown by pedigree studies, comparison of genetic stocks raised in the same environment, and selection experiments. The knowledge of gene polymorphisms responsible for genetic variability would increase the efficiency of selection, as shown for instance by the identification of the ryanodine receptor gene that harbours the mutations responsible for the porcine stress syndrome, that allows the eradication of the susceptibility allele. One strategy is to screen systematically the genes that are known to be involved in regulation of behaviour (functional candidate genes). This strategy is however very difficult for most behavioural traits, since behaviour is an emerging function from the whole brain/body and the molecular pathways involved in genetic variability are very poorly understood. Another strategy is to investigate linkage between trait variation and genetic markers in a segregating population (usually an intercross or backcross between two strains or breeds contrasting for the trait under study). It allows the detection of genomic regions influencing that trait (quantitative trait loci or QTL), and further investigation aims at the identification of the gene(s) located in each of these regions and the molecular polymorphisms involved in phenotypic variation. Although many QTL have been published for behavioural traits in experimental animals, very few examples are available where strong candidate genes have been identified. Further progress will be very much dependent upon the careful definition of behavioural traits to be studied (including their importance for animal production), on the reliability of their measurement in a large number of animals and on the efficient mastering of environmental factors of variability. The fast increase in the knowledge of genome sequence in several species will undoubtedly facilitate the application to farm animal species of the knowledge obtained in model organisms, as well as the use of model organisms to explore candidate genes detected by QTL studies in farm animals.     

Genetic correlations between categorical morphological traits in Nelore cattle by applying Bayesian analysis under a threshold animal model

In this study, Bayesian analysis under a threshold animal model was used to estimate genetic correlations between morphological traits (body structure, finishing precocity and muscling) in Nelore cattle evaluated at weaning and yearling. Visual scores obtained from 7651 Nelore cattle at weaning and from 4155 animals at yearling, belonging to the Brazilian Nelore Program, were used. Genetic parameters for the morphological traits were estimated by two‐trait Bayesian analysis under a threshold animal model. The genetic correlations between the morphological traits evaluated at two ages of the animal (weaning and yearling) were positive and high for body structure (0.91), finishing precocity (0.96) and muscling (0.94). These results indicate that the traits are mainly determined by the same set of genes of additive action and that direct selection at weaning will also result in genetic progress for the same traits at yearling. Thus, selection of the best genotypes during only one phase of life of the animal is suggested. However, genetic differences between morphological traits were better detected during the growth phase to yearling. Direct selection for body structure, finishing precocity and muscling at only one age, preferentially at yearling, is recommended as genetic differences between traits can be detected at this age.     

Primates as experimental animals

The term "primates" comprises a varied group of animals, consisting of more than 250 different species. The close evolutionary relationship to man resulted in the use of nonhuman primates as subjects of study for scientists from different research fields. In biomedical research the use of primates is restricted to questions which cannot be answered by animals with less developed physiological senses. Primates play an important role in infectious disease research, as many pathogens relevant to humans can be transferred to selected primate species. In the last few decades this applied especially for HIV-infections of man, viral hepatitides, herpesvirus infections and for quite a long time for agents of transmissible spongiform encephalopathies, too. In neurobiology, primates play an outstanding role due to the morphological-structural and functional resemblance of their CNS to that of man. Due to new developments in biomedicine, in particular in the field of gene therapeutics, it has to be expected that primates will have to be used also in future as animal models for the welfare of human health.     

Stress Reactivity and Coping in Horse Adaptation to Environment

“Coping” or “coping strategy”, defined as the behavioral and physiological efforts of animal to master the situation, is more and more in interest of researchers dealing with applied animal behavior and welfare. Knowledge about “coping styles” may be helpful in understanding individual adaptive capacity to stressful events. At least two types of animal coping strategy (or coping style) can be involved: (1) active copers (proactive) and (2) passive copers (reactive). The individual differences in stress response to threatening situations have been found in horses, and these animals can show specific coping strategies such as other species. This article reviews the set of behavioral, psychoneuroendocrine, and psychoneuroimmune mechanisms involved in animal adaptation to environmental challenges and discusses the relationship between behavioral and physiological factors involved in stress response of the horse. Exploring coping strategies in horses and in any captive animal can be successful when a multidimensional approach including behavioral, neural, hormonal, and hematological measures is considered. Knowledge on stress coping styles can provide valuable information to predict the behavior of individuals during response to specific challenging situations. Moreover, assessing individual differences in adaptation strategies can be useful in horse selection to different exploitation tasks and reproduction.     

犬品种之间的药物遗传和代谢差异

描述动物物种的相关药理学遗传差异的资料非常有限。尽管在兽医药学的遗传信息缺乏,但品种对内在的和外在的物质的具体反应已经有许多物种的报告。这一发现强调了当前跨越品种获得洞察基因型和表型变异的重要性。本文提供了有关犬品种在生理学,药物反应,药物药代动力学和代谢特性方面的差异的文献总结。了解这些品种差异将改善犬的人口预测（为了犬的药物产品）,当推断从犬到人类的毒理学数据时可能是有价值的。     

Pharmacogenetics of opioid analgesics in dogs

Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine. This review discusses the opioid drug metabolism and possible genetic polymorphism of metabolizing enzymes in dogs. Polymorphism of genes encoding opioid drug transporter proteins and its effect on opioid response and opioid receptor gene variants are also discussed. Due to the scarcity of studies reported on opioid pharmacogenetics in dogs, relevant studies in humans and rodents have also been discussed to indicate current trends and potential targets for research in dogs.     

Canine fertility: The consequences of selection for special traits

Pedigree dogs and cats are bred aiming to conform breed standards with very poor consideration for breeding stock fertility. At the same time, the genetic asset underlining reproductive traits could be effectively analysed like in other species under selection. The definition of selection targets is very important in breeding protocols determination. The aim of the present work is to present an overview of the different correlations between reproduction and genetics, starting from selection procedure and inbreeding coefficient moving to genomic and the application of SNPs and GWAS on population study and identification of genes involved in phenotypical variation of reproductive traits in dogs. Particular relevance has been given to the concept of inbreeding which effects on canine reproduction have been presented. The use of genomic information in inbreeding coefficient calculation can be considered an improved effective procedure in the evaluation of the genetic variability loss in canine population and its negative effects on reproductive traits.     

角蛋白家族基因及其与动物毛发性状关系的研究进展

角蛋白基因家族由众多结构和功能相似的基因组成,分为角蛋白中间丝蛋白(KIF)和角蛋白关联蛋白(KAP)2个基因家族.角蛋白是动物毛发的结构蛋白,决定毛发纤维的基本特征,是在寻找控制毛皮性状主效基因时的首选候选基因.角蛋白基因的表达与遗传多样性有关,角蛋白的多态性与毛皮动物的毛发性状具有相关性.本文从角蛋白基因的结构与定...