Recent advances in small animal genetics.

The whole genome sequence of the dog is complete, and partial sequencing of the cat genome is underway. Sequences allow the molecular basis for inherited diseases to be more easily determined, leading to development of DNA tests to verify carrier and affected states as well as potential gene therapy for the treatment of those diseases. To help veterinarians provide genetic services to their clients, the molecular genetic tests currently available are listed in this article. In addition, cloning of small animals is now available to clients on a commercial basis. Information about the cloning process and possible health issues in clones are discussed.     

Give a dog a genome

In 2004 the dog became only the fifth mammal to have its entire genome fully sequenced. The canine genome was sequenced in the hope that it would help scientists understand the complex evolutionary mechanisms that shape genes and genomes and provide a powerful tool for identifying genetic factors that contribute to human health and disease. It is expected that over the coming years the genome of man's best friend will help in the understanding of the genetic cause of many inherited diseases that humans and dogs have in common. Not only of obvious benefit to humans, these studies will enable the development of DNA diagnostic tests that breeders can use to identify which of their dogs carry mutations that put them at risk of developing particular conditions and thus, over time, eliminate those diseases from the breed.     

Finding cardiovascular disease genes in the dog

Recent advances in canine genomics are changing the landscape of veterinary biology, and by default, veterinary medicine. No longer are clinicians locked into traditional methods of diagnoses and therapy. Rather, major advances in canine genetics and genomics from the past five years are now changing the way the veterinarian of the 21st century practices medicine. First, the availability of a dense genome map gives canine genetics a much-needed foothold in comparative medicine, allowing advances made in human and mouse genetics to be applied to companion animals. Second, the recently released 7.5× whole genome sequence of the dog is facilitating the identification of hereditary disease genes. Finally, development of genetic tools for rapid screening of families and populations at risk for inherited disease means that the cost of identifying and testing for disease loci will significantly decrease in coming years. Out of these advances will come major changes in companion animal diagnostics and therapy. Clinicians will be able to offer their clients genetic testing and counseling for a myriad of disorders. In this review we summarize recent findings in canine genomics and discuss their application to the study of canine cardiac health.     

LUPA: a European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs

The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism for comparative disease genetics. Using newly developed resources, genome-wide association studies in dog breeds are proving to be exceptionally powerful. Towards this aim, veterinarians and geneticists from 12 European countries are collaborating to collect and analyse the DNA from large cohorts of dogs suffering from a range of carefully defined diseases of relevance to human health. This project, named LUPA, has already delivered considerable results. The consortium has collaborated to develop a new high density single nucleotide polymorphism (SNP) array. Mutations for four monogenic diseases have been identified and the information has been utilised to find mutations in human patients. Several complex diseases have been mapped and fine mapping is underway. These findings should ultimately lead to a better understanding of the molecular mechanisms underlying complex diseases in both humans and their best friend.     

家犬基因组及表型特征的遗传研究进展

犬具有丰富的遗传多样性,犬、人和鼠3种生物的基因组分析发现,犬与人、鼠的保守性非常高。犬的特殊群体结构使其成为研究形态、行为等多样性、哺乳动物进化遗传基础和疾病的良好模型。本文就家犬起源进化、基因组结构、犬表型特征的遗传变异、基因定位等研究进展做一综述,以期为犬遗传育种研究提供理论基础,并为人类疾病的预防、诊断和治疗提供新的思路与方法。     

Non-lactational traits of importance in dairy cows and applications for emerging biotechnologies

Dairy cattle have traditionally been selected for their ability to produce milk and milk components. The traditional single-minded approach to selection of dairy cattle has now changed and secondary traits are being included in selection indices by decreasing the emphasis on production. Greater emphasis on non-production traits reflects the industry's desire for functional dairy cattle. Six broad categories of non-lactational traits are discussed in this review. They are: type; growth, body size and composition; efficiency of feed utilisation; disease resistance, e.g. udder health as measured by somatic cell score; reproduction; and management. Most of these traits can be found within selection indices worldwide, although relative emphasis varies.

The non-lactational traits mentioned above are quantitative, meaning that the phenotype in the whole animal represents the sum of lesser traits that cannot be easily measured. The physiological mechanisms that underlie quantitative traits are extremely complex. Genetic selection can be applied to quantitative traits but it is difficult to link successful genetic selection with the underlying physiological mechanisms. The importance that the bovine genome sequence will play in the future of the genetics of dairy cattle cannot be understated. Completing the bovine genome sequence is the first step towards modernising our approach to the genetics of dairy cattle.

Finding genes in the genome is difficult and scanning billions of base pairs of DNA is an imperfect task. The function of most genes is either unknown or incompletely understood. Combining all of the information into a useable format is known as bioinformatics. At the present time, our capacity to generate information is great but our capacity to understand the information is small. The important information resides within subtle changes in gene expression and within the cumulative effect that these have.

Traditional methods of genetic selection in dairy cattle will be used for the foreseeable future. Most non-lactational traits are heritable and will be included in selection indices if the traits have value. The long-term prognosis for genome science is good but advances will take time. Genetic selection in the genome era will be different because DNA sequence analysis may replace traditional methods of genetic selection.     

Polymorphic microsatellite markers for genetic analysis of collagen genes in suspected collagenopathies in dogs

Defects in collagen proteins cause a variety of disorders in humans. It can be expected that collagen gene mutations are involved in collagenopathies in dogs. The collagen genes COL3A1, COL5A1, COL5A2, COL6A1, COL6A3, COL9A1, COL9A2, COL9A3, COL10A1 and COL11A1 were identified on the canine genome based on the homology with the human genes. Simple sequence repeats (microsatellites) were found in the chromosomal regions of these genes and investigated for polymorphism in Labrador Retrievers, Bernese Mountain dogs, Boxer dogs and German Shepherd dogs by PCR and subsequent detection of the DNA products. Nine informative microsatellite markers were identified. The markers closely situated to COL9A1, COL9A2 and COL9A3 were used to investigate the involvement of the genes in cranial cruciate ligament rupture in Boxer dogs. It was found that these genes are probably not involved in this abnormality. The markers described here will be useful for a candidate gene approach of suspected collagenopathies specific to dog breeds.     

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.     

Characterization of canine filaggrin: gene structure and protein expression in dog skin

Background – Filaggrin (FLG) is a key protein for skin barrier formation and hydration of the stratum corneum. In humans, a strong association between FLG gene mutations and atopic dermatitis has been reported. Although similar pathogenesis and clinical manifestation have been argued in canine atopic dermatitis, our understanding of canine FLG is limited. Hypothesis/Objectives – The aim of this study was to determine the structure of the canine FLG gene and to raise anti‐dog FLG antibodies, which will be useful to detect FLG protein in dog skin. Methods – The structure of the canine FLG gene was determined by analysing the publicly available canine genome DNA sequence. Polyclonal anti‐dog FLG antibodies were raised based on the canine FLG sequence analysis and used for defining the FLG expression pattern in dog skin by western blotting and immunohistochemistry. Results – Genomic DNA sequence analysis revealed that canine FLG contained four units of repeated sequences corresponding to FLG monomer protein. Western blots probed with anti‐dog FLG monomer detected two bands at 59 and 54 kDa, which were estimated sizes. The results of immunohistochemistry showed that canine FLG was expressed in the stratum granulosum of the epidermis as a granular staining pattern in the cytoplasmic region. Conclusions and clinical importance – This study revealed the unique gene structure of canine FLG that results in production of FLG monomers larger than those of humans or mice. The anti‐dog FLG antibodies raised in this study identified FLG in dog skin. These antibodies will enable us to screen FLG‐deficient dogs with canine atopic dermatitis or ichthyosis.     

Genetics of canine diabetes mellitus: Are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs?

Diabetes mellitus is a common endocrinopathy in companion animals, characterised by hyperglycaemia, glycosuria and weight loss, resulting from an absolute or relative deficiency in the pancreatic hormone insulin. There are breed differences in susceptibility to diabetes mellitus in dogs, with the Samoyed breed being overrepresented, while Boxers are relatively absent in the UK population of diabetic dogs, suggesting that genetic factors play an important role in determining susceptibility to the disease. A number of genes, linked with susceptibility to diabetes mellitus in humans, are associated with an increased risk of diabetes mellitus in dogs, some of which appear to be relatively breed-specific. Diabetes mellitus in dogs has been associated with major histocompatibility complex (MHC) class II genes (dog leucocyte antigen; DLA), with similar haplotypes and genotypes being identified in the most susceptible breeds. A region containing a variable number of tandem repeats (VNTR) and several polymorphisms have been identified in the canine insulin gene, with some alleles associated with susceptibility or resistance to diabetes mellitus in a breed-specific manner. Polymorphisms in the canine CTLA4 promoter and in other immune response genes are associated with susceptibility to diabetes mellitus in a number of pedigree breeds. Genome wide association studies are currently underway that should shed further light on the genetic factors responsible for the breed profile seen in the diabetic dog population.     

An update on canine coronaviruses: viral evolution and pathobiology

The emergence of human severe acute respiratory syndrome incited renewed interest in animal coronaviruses (CoVs) as potential agents of direct and indirect zoonoses. The reinforced epidemiological surveillance on CoVs has led to the identification of new viruses, genotypes, pathotypes and host variants in animals and humans. In dogs, a CoV associated with mild enteritis, canine coronavirus (CCoV), has been known since 1970s. CoV strains with different biological and genetic properties with respect to classical CCoV strains have been identified in dogs in the last few years, leading to a full reconsideration of the CoV-induced canine diseases. The genetic evolution of dog CoVs is paradigmatic of how CoVs evolve through accumulation of point mutations, insertions or deletions in the viral genome, that led to the emergence of new genotypes (CCoV type I), biotypes (pantropic CCoV) and host variants (canine respiratory coronavirus). This paper is a review of the current literature on the recent genetic evolution of CCoV and emergence of new CoVs in the dog. The significances of the newly acquired information for the canine health status and prophylaxis programmes are also discussed.     

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.     

Canine and human factors related to dog bite injuries

OBJECTIVE: To identify physical traits of biting dogs and characteristics of injured persons and dog owners associated with bite situations for use in public health prevention activities. DESIGN: Retrospective cohort study. STUDY POPULATION: Licensed dog and dog bite report data from June 30, 2002, to July 1, 2003, that were obtained from Animal Control Services of Multnomah County, Oregon. PROCEDURES: To determine the canine and human factors associated with dog bite injuries, the number of bites, dog and injured person characteristics, and the overall canine population were evaluated. Dog owner characteristics at the block group level were defined by use of geographic information system software through 2000 census information based on place of residence. RESULTS: During the study period, 636 dog bites were reported to Animal Control Services, and 47,526 dogs were licensed in Multnomah County. Risk factors associated with biting dogs included breed (terrier, working, herding, and nonsporting breeds), being a sexually intact male, and purebred status. Male children aged 5 to 9 years had the highest rate of injury (178 bites/100,000 children). Biting dogs were more likely than nonbiting dogs to live in neighborhoods where the residents' median incomes were less than the county median income value ($41,278). CONCLUSIONS AND CLINICAL RELEVANCE: Dog bites continue to be a source of preventable injury. Prevention programs should target owners of sexually intact male and purebred dogs and owners who live in lower income neighborhoods.     

Exaggerated breed characteristics in dogs

Dutch dog owners seem to be aware of bad dog breeding practices with regard to exaggerated breed characteristics that are detrimental to the dog's welfare. Yet they do not always look for these features when buying a dog. Most dog owners think that veterinarians could have an important role in preventing these exaggerated physical traits, by providing information about these traits and taking action in their capacity as veterinarian. Articles 36 and 55 of the Dutch GWWD (animal health and welfare law) provide opportunities to act against the breeding of dogs with exaggerated genetic traits.     

Healthy pets, healthy people.

Zoonoses, diseases that can be transmitted from animals to humans, can pose serious health risks to immunocompromised people. Although pets can carry zoonoses, owning and caring for animals can benefit human health. Information exists about preventing transmission of zoonoses, but not all physicians and veterinarians provide adequate and accurate information to immunocompromised pet owners. This disease prevention/health promotion project provides physicians and veterinarians with information, created specifically to share with patients and clients, about the health risks and benefits of pet ownership. Further, "Healthy Pets, Healthy People" encourages communication between veterinarians, physicians, clients, and patients and can serve as a model program for a nation-wide effort to aid health professionals in making recommendations about pet ownership for immunocompromised people.     

Development of DNA markers for improvement of meat quality in a Japanese Black cattle population in Hyogo Prefecture

The polymorphisms associated with economic traits in livestock animals provide useful information as genetic indicators for breeding improvement. Over the last two decades, several DNA markers have been developed in Japanese Black cattle; however, the effect of these markers differs across populations due to differences in their genetic structures and backgrounds. As such, there is a need to verify the effectiveness of these markers in each population. This review summarizes the effectiveness of previously reported markers on carcass traits and the development of novel DNA markers in a Japanese Black cattle population in Hyogo Prefecture. As result of genome wide association studies and resequencing analyses, two novel significant markers associated with meat quality-related traits (beef marbling and fatty acid composition) were developed. These findings will lead to the identification of responsible genes and polymorphisms and contribute to the development of novel DNA markers for numerous traits in various cattle populations.     

昆明犬群体遗传结构及受选择基因分析

旨在以昆明犬为主要研究对象探究昆明犬-国内唯一培育并广泛使用的工作犬品种的遗传多样性和群体遗传结构。本试验共采集16头昆明犬(3个品系)、4头马里努阿犬、4头德国牧羊犬血样并提取基因组DNA，用Illumina CanineHD Beadchip芯片对24头3个品种犬进行主成分分析(PCA)、STRUCTURE和邻接(NJ)树分析，检测3个品种警犬的遗传群体结构，并分析昆明犬选育中可能受到选择的候选基因。结果显示，芯片数据根据质控标准最终有86 270个SNPs被筛选出来用于分析。STRUCTURE群体结构分析表明，K=2时德国牧羊犬(DM)和其他品种犬完全区分开来，K=3时马里努阿犬(ML)可以和其他两个品种区分出来，昆明犬中存在部分德国牧羊犬的杂合。PCA和NJ树分析均能将3个品种犬清楚地分开。通过在常染色体上设置500 kb的滑动窗口和将这些区域注释后得到22个在昆明犬品种形成过程中可能受到正选择的基因，主要是参与腺苷酸环化酶活化g蛋白偶联受体信号通路的基因及蛋白和在神经元轴突的生长锥中影响轴突和前导突起生长的基因。本研究探讨了中国昆明犬与其他品种犬的遗传关系,为昆明犬受到强烈的人工选择而产生调节学习、记忆、应激刺激等适应的遗传机制提供了重要的参考。     

Current Status of Genetic Studies of Exocrine Pancreatic Insufficiency in Dogs

Exocrine pancreatic insufficiency (EPI) is a disorder wherein the pancreas fails to secrete adequate amounts of digestive enzymes. In dogs, EPI is usually the consequence of an autoimmune disease known as pancreatic acinar atrophy. Originally believed to be a simple autosomal recessive disorder, a test-breeding recently revealed that EPI has a more complex mode of inheritance. The contributions of multiple genes, combined with environmental factors, may explain observed variability in clinical presentation and progression of this disease. Research efforts aim to identify genetic variations underlying EPI to assist breeders in their efforts to eliminate this disease from their breed and provide clinicians with new targets for therapeutic intervention and/or disease prevention. Genome-wide linkage, global gene expression, and candidate gene analyses have failed to identify a major locus or genetic variations in German Shepherd Dogs with EPI. Recently, genome-wide association studies revealed numerous genomic regions associated with EPI. Current studies are focused on alleles of the canine major histocompatibility complex. In this article we review findings from scientific investigations into the inheritance and genetic cause(s) of EPI in the purebred dog.     

DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia,modelling human myeloid leukaemia

Tumours shows aberrant DNA methylation patterns, being hypermethylated or hypomethylated compared with normal tissues. In human acute myeloid leukaemia (hAML) mutations in DNA methyltransferase (DNMT3A) are associated to a more aggressive tumour behaviour. As AML is lethal in dogs, we defined global DNA methylation content, and screened the C‐terminal domain of DNMT3 family of genes for sequence variants in 39 canine acute myeloid leukaemia (cAML) cases. A heterogeneous pattern of DNA methylation was found among cAML samples, with subsets of cases being hypermethylated or hypomethylated compared with healthy controls; four recurrent single nucleotide variations (SNVs) were found in DNMT3L gene. Although SNVs were not directly correlated to whole genome DNA methylation levels, all hypomethylated cAML cases were homozygous for the deleterious mutation at p.Arg222Trp. This study contributes to understand genetic modifications of cAML, leading up to studies that will elucidate the role of methylome alterations in the pathogenesis of AML in dogs.     

Survey of veterinarians' recommendations for treatment and control of intestinal parasites in dogs: public health implications

A systematic, random sample of 450 small and mixed-animal practitioners was selected from the client list of a prominent veterinary pharmaceutical and animal health company. A telephone survey was conducted, using a standard questionnaire, to assess whether current veterinary practices concerning prophylaxis and treatment of canine roundworm (Toxocara canis) and hookworm (Ancylostoma spp) infections are adequate to prevent transmission to human beings. Analysis of results focused on 3 questions related to prevention: practitioner's frequency of client education regarding zoonotic potential of roundworms and hookworms, pup age at which veterinarian recommends first anthelmintic treatments, and proportion of veterinarians recommending prophylactic drug administration for pups and nursing bitches. Despite the proven association of household pet dogs and human toxocariasis, only a third (148/450) of veterinarian respondents routinely discussed the potential zoonotic hazards of canine roundworms with their clients. A total of 29% (130/450) of veterinarians surveyed either never discussed these potential hazards or discussed them only when asked by their clients. With regard to anthelmintic treatment practices, 31% (140/450) of veterinarians surveyed recommended that pups first be examined and treated for intestinal parasites within 4 weeks of age. Thirty-three percent (163/450) recommended first examination and deworming at 5 to 6 weeks of age, and 36% (163/450) suggested that it be done at or after 7 weeks of age. Less than half (208/450) of veterinarians administered anthelmintics prophylactically to at least some pups and dogs. Sixty-four percent (287/450) of respondents recommended routine testing and treatment of nursing bitches.(ABSTRACT TRUNCATED AT 250 WORDS)