Canine genetics and epidemiology最新文献

Background: Canine DNA-testing has become an important tool in purebred dog breeding and many breeders use genetic testing results when planning their breeding strategies. In addition, information obtained from testing of hundreds dogs in one breed gives valuable information about the breed-wide genotype frequency of disease associated allele. Lafora disease is a late onset, recessively inherited genetic disease which is diagnosed in Miniature Wirehaired Dachshunds (MWHD). It is one of the most severe forms of canine epilepsy leading to neurodegeneration and, frequently euthanasia within a few years of diagnosis. Canine Lafora disease is caused by a dodecamer repeat expansion mutation in the NHLRC1 gene and a DNA test is available to identify homozygous dogs at risk, carriers and dogs free of the mutation.

Results: Blood samples were collected from 733 MWHDs worldwide, mostly of UK origin, for canine Lafora disease testing. Among the tested MWHD population 7.0% were homozygous for the mutation and at risk for Lafora disease. In addition, 234 dogs were heterozygous, indicating a carrier frequency of 31.9% in the tested population. Among the tested MWHDs, the mutant allele frequency was 0.2. In addition, data from the tested dogs over 6 years (2012-2017) indicated that the frequency of the homozygous and carrier dogs has decreased from 10.4% to 2.7% and 41.5% to 25.7%, respectively among MWHDs tested. As a consequence, the frequency of dogs free of the mutation has increased from 48.1% to 71.6%.

Conclusions: This study provides valuable data for the MWHD community and shows that the DNA test is a useful tool for the breeders to prevent occurrence of Lafora disease in MWHDs. DNA testing has, over 6 years, helped to decrease the frequency of carriers and dogs at risk. Additionally, the DNA test can continue to be used to slowly eradicate the disease-causing mutation in the breed. However, this should be done carefully, over time, to avoid further compromising the genetic diversity of the breed. The DNA test also provides a diagnostic tool for veterinarians if they are presented with a dog that shows clinical signs associated with canine Lafora disease.

Background: The selection of a future breeding dog is a complicated task, in which disease characteristics and different traits have to be combined and weighed against one another. Truncation selection, that is the exclusion of affected animals, may be very inefficient when selecting on a large number of traits, and may result in a reduction of the genetic diversity in a population or breed. Selection could be facilitated by the use of a selection index that combines multiple traits or breeding values into one score. This however requires a consideration of their relative value according to their economic weight, which is difficult to express in monetary units for health traits. The use of a choice experiment to derive non-market values might be a solution to this problem. This is a pilot study to assess the potential use of choice experiments to ascertain the public preference and relative importance attached to health- and conformation traits in the selection of a Cavalier King Charles spaniel. The focus was on two prevalent disorders, mitral valve disease and syringomyelia, and on several important conformation traits such as muzzle length and eye shape. Based on available prior information, a Bayesian D-optimal design approach was used to develop a choice experiment and the resulting choice sets.

Results: Every participant (breeder or owner) in the choice experiment was presented with a total of 17 choice sets, in which at most four traits could vary to reduce the cognitive burden. A total of 114 respondents participated in the choice experiment and results showed that respondents (breeders/owners) current attitudes were directed towards health (syringomyelia and mitral valve disease), followed by eye shape and level of inbreeding.

Conclusions: This approach identifies the value breeders and owners attach to certain traits in the breeding objective. The resulting relative weights, represented as the logworths obtained from the choice experiment, could be an alternative to economic weights. They could be implemented as a weight when breeding values are available, but more study on this topic will be necessary. A challenge in this approach is to scale up the experiment with additional traits. Moreover, for other traits, the genetic parameters and correlations should be known first, in order to include them in the health selection index as well.

Background: Breed-related health problems in dogs have received increased focus over the last decade. Responsibility for causing and/or solving these problems has been variously directed towards dog breeders and kennel clubs, the veterinary profession, welfare scientists, owners, regulators, insurance companies and the media. In reality, all these stakeholders are likely to share some responsibility and optimal progress on resolving these challenges requires all key stakeholders to work together. The International Partnership for Dogs (IPFD), together with an alternating host organization, holds biennial meetings called the International Dog Health Workshops (IDHW). The Société Centrale Canine (French Kennel Club) hosted the 3rd IDHW, in Paris, in April, 2017. These meetings bring together a wide range of stakeholders in dog health, science and welfare to improve international sharing of information and resources, to provide a forum for ongoing collaboration, and to identify specific needs and actions to improve health, well-being and welfare in dogs.

Results: The workshop included 140 participants from 23 countries and was structured around six important issues facing those who work to improve dog health. These included individualized breed-specific strategies for health and breeding, extreme conformations, education and communication in relation to antimicrobial resistance, behavior and welfare, genetic testing and population-based evidence. A number of exciting actions were agreed during the meeting. These included setting up working groups to create tools to help breed clubs accelerate the implementation of breed-health strategies, review aspects of extreme conformation and share useful information on behavior. The meeting also heralded the development of an online resource of relevant information describing quality measures for DNA testing. A demand for more and better data and evidence was a recurring message stressed across all themes.

Conclusions: The meeting confirmed the benefits from inclusion of a diverse range of stakeholders who all play relevant and collaborative parts to improve future canine health. Firm actions were set for progress towards improving breed-related welfare. The next international workshop will be in the UK in 2019 and will be organized by the UK Kennel Club.

Background: The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme.

Results: Annual birth proportion for Border Terriers showed a decreasing trend from 1.46% in 2005 to 0.78% in 2014. The median adult bodyweight for males (10.9 kg, IQR: 9.6-12.3, range: 6.3-25.0) was higher than for females (9.1 kg, IQR: 8.2-10.3, range: 5.2-21.6) (P < 0.001). The median longevity was 12.7 years (IQR 9.3-14.3, range 1.0-17.5).The most prevalent fine-level disorders recorded were periodontal disease (17.63%, 95% CI: 15.62-19.79), overweight/obesity (7.01%, 95% CI: 5.69-8.52) and otitis externa (6.71%, 95% CI: 5.42-8.19). The most prevalent grouped-level precision disorders were dental disorder (18.54%, 95% CI: 16.48-20.74), enteropathy (11.68%, 95% CI: 10.00-13.53), and skin disorder (10.17%, 95% CI: 8.60-11.93).Syndromic analysis showed that the most prevalent body locations affected were the head-and-neck (37.75%, 95% CI: 35.14-40.43), abdomen (18.61%, 95% CI: 16.55-20.81) and limb (11.53%, 95% CI: 9.86-13.37). At least one organ system was affected in 834 (62.85%) Border Terriers. The most prevalent organ systems affected were the digestive (32.03%, 95% CI: 29.52-34.61), integument (26.68%, 95% CI: 24.31-29.14), connective/soft tissue (11.15%, 95% CI: 9.51-12.97) and auditory (9.87%, 95% CI: 8.32-11.60). At least one affected pathophysiological process was described in 881 (66.39%) Border Terriers. The most prevalent pathophysiologic processes recorded were inflammation (31.65%, 95% CI: 29.15-34.23), nutritional (9.04%, 95% CI: 7.55-10.72), mass/swelling (8.89%, 95% CI: 7.42-10.55), traumatic (7.99%, 95% CI: 6.59-9.58) and infectious (7.76%, 95% CI: 6.38-9.33).

Conclusions: This study documented a trend towards reducing ownership and relatively long-livedness in the Border Terrier. The most common disorders were periodontal disease, overweight/obesity and otitis externa. Predisposition to dental and neurological disease was suggested. These results can provide a comprehensive evidence resource to support breed-based health plans that can contribute positively to reforms to improve health and welfare within the breed.

Background: Pure breeding of dogs has led to over 700 heritable disorders, of which almost 300 are Mendelian in nature. Seventy percent of the characterized mutations have an autosomal recessive mode of inheritance, indicative of positive selection during bouts of inbreeding primarily for new desired conformational traits. Samoyed suffer from several common complex genetic disorders, but up to this time only two X-linked and one autosomal dominant disorder have been identified. Previous studies based on pedigrees and SNP arrays have concluded that Samoyed breeders have done a good job in maintaining genetic diversity and avoiding excessive inbreeding. This may explain why autosomal recessive disorders have not occurred to the extent observed in many other breeds. However, an enamel hypoplasia analogous to a form of autosomal recessive amelogenesis imperfecta (ARAI) in humans has been recently characterized in Samoyed, although the causative mutation appears to have existed for three or more decades. The rise of such a mutation indicates that bouts of inbreeding for desired conformational traits are still occurring despite an old and well-defined breed standard. Therefore, the present study has two objectives: 1) measure genetic diversity in the breed using DNA and short tandem repeats (STR), and 2) identify the exact mutation responsible for enamel hypoplasia in the breed, possible explanations for its recent spread, and the effect of eliminating the mutation on existing genetic diversity.

Results: The recent discovery of an autosomal recessive amelogenesis imperfecta (ARAI) in Samoyed provides an opportunity to study the mutation as well as genetic factors that favored its occurrence and subsequent spread. The first step in the study was to use 33 short tandem repeat (STR) loci on 25/38 autosomes and seven STRs across the dog leukocyte antigen (DLA) class I and II regions on CFA12 to determine the DNA-based genetic profile of 182 individuals from North America, Europe and Australia. Samoyed from the three continents constituted a single breed with only slight genetic differences. Breed-wide genetic diversity was low, most likely from a small founder population and subsequent artificial genetic bottlenecks. Two alleles at each autosome locus occurred in 70-95% of the dogs and 54% of alleles were homozygous. The number of DLA class I and II haplotypes was also low and three class I and two class II haplotypes occurred in 80-90% of individuals. Therefore, most Samoyed belong to two lines, with most dogs possessing a minority of existing genetic diversity and a minority of dogs containing a majority of diversity. Although contemporary Samoyed lack genetic diversity, the bulk of parents are as unrelated as possible with smaller subpopulations either more inbred or outbred than the total population. A familial disorder manifested by hypocalcification of enamel has been recently identified. A genome wide assoc

Background: Rottweilers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Rottweilers under UK veterinary care. Clinical health records within the VetCompass Programme were explored for disorders recorded during 2013.

Results: Rottweilers comprised 5321 (1.17%) of 455,557 dogs attending 304 clinics. Annual proportional birth rates dropped from 1.75% in 2006 to 1.07% in 2013. Median adult bodyweight overall was 44.9 kg (IQR 39.55-51.00, range 20.00-88.80). Median male adult bodyweight (48.5 kg, interquartile range [IQR] 43.0-54.0, range 20.0-88.8) was heavier than female (41.5 kg, IQR 37.0-46.4, range 21.1-73.5) (P < 0.001). Median longevity overall was 9.0 years (IQR 7.2-10.5, range 0.0-17.0). Median female longevity (9.5 years, IQR 7.8-11.0) was greater than male (8.7 years, IQR 6.8-10.1) (P = 0.002). The most common causes of death were neoplasia (33.0%), inability to stand (16.0%) and mass-associated disorder (7.1%).At least one disorder was recorded for 60.31% of Rottweilers. The most prevalent specific disorders recorded were aggression (7.46%, 95% CI 6.40-8.64), overweight/obesity (7.06%, 95% CI: 6.02-8.21), otitis externa (6.14%, 95% CI: 5.18-7.23) and degenerative joint disease (4.69%, 95% CI: 3.84-5.66). Male Rottweilers had higher prevalence than females for aggression (9.36% versus 5.47%, P = 0.001) and pyotraumatic dermatitis (4.05% versus 1.76%, P = 0.001). Aggression was more prevalent in neutered than entire females (7.5% versus 3.1%, P = 0.003) but did not differ between neutered and entire males (9.6% versus 9.0%, P = 0.773). The most frequent disorder groups were musculoskeletal (12.01%, 95% CI: 10.69-13.45), dermatological (10.96%, 95% CI: 9.69-12.35), gastro-intestinal (195, 8.87%, 95% CI: 7.72-10.14), undesirable behaviour (7.96%, 95% CI: 6.87-9.18) and neoplasia (7.96%, 95% CI: 6.87-9.18).

Conclusions: The current study assists prioritisation of health issues within Rottweilers. Rottweilers are relatively short-lived and neoplasia is a common cause of death. The most common disorders were aggression, overweight/obesity, otitis externa and degenerative joint disease. Males were significantly heavier, shorter-lived and predisposed to aggression than females. These results can alert prospective owners to potential health issues and optimise sex selection decision-making.

Background: Studying cancer and other diseases poses a problem due to their protracted and multifactorial nature. Prospective studies are useful to investigate chronic disease processes since collection of lifestyle information, exposure data and co-incident health issues are collected before the condition manifests. The Golden Retriever Lifetime Study is one of the first prospective studies following privately-owned dogs throughout life to investigate the incidence and risk factors for disease outcomes, especially cancer.Owners of golden retrievers in the contiguous United States volunteered their dogs in early life. Owners and veterinarians complete online questionnaires about health status and lifestyle; dogs undergo a physical examination and collection of biological samples annually. The data presented summarize the initial study visits and the corresponding questionnaires for 3044 dogs in the cohort.

Results: The median age of dogs at enrollment was 14.0 months (interquartile range (IQR): 8-20 months). Approximately half of the population had undergone gonadectomy by their initial study visit. Medical conditions reported at enrollment consisted primarily of integumentary, gastrointestinal and urinary dysfunction. A large majority of the dogs have a record of having received preventive care (vaccines, parasiticides, flea and heartworm prevention) by the time of the initial study visit. Clinical pathology data were unremarkable.

Conclusions: This study represents one of the first lifetime observational investigations in veterinary medicine. The population characteristics reported here indicate a healthy cohort of golden retrievers cared for by owners committed to their dogs' health. Data acquired over the study period will provide valuable information about genetic, dietary and environmental risk factors associated with disease in golden retrievers and a framework for future prospective studies in veterinary medicine.

Background: Canine lumbosacral stenosis is defined as narrowing of the caudal lumbar and/or sacral vertebral canal. A risk factor for neurologic problems in many large sized breeds, lumbosacral stenosis can also cause early retirement in Labrador retriever military working dogs. Though vital for conservative management of the condition, early detection is complicated by the ambiguous nature of clinical signs of lumbosacral stenosis in stoic and high-drive Labrador retriever military working dogs. Though clinical diagnoses of lumbosacral stenosis using CT imaging are standard, they are usually not performed unless dogs present with clinical symptoms. Understanding the underlying genomic mechanisms would be beneficial in developing early detection methods for lumbosacral stenosis, which could prevent premature retirement in working dogs. The exomes of 8 young Labrador retriever military working dogs (4 affected and 4 unaffected by lumbosacral stenosis, phenotypically selected by CT image analyses from 40 dogs with no reported clinical signs of the condition) were sequenced to identify and annotate exonic variants between dogs negative and positive for lumbosacral stenosis.

Results: Two-hundred and fifty-two variants were detected to be homozygous for the wild allele and either homozygous or heterozygous for the variant allele. Seventeen non-disruptive variants were detected that could affect protein effectiveness in 7 annotated (SCN1B, RGS9BP, ASXL3, TTR, LRRC16B, PTPRO, ZBBX) and 3 predicted genes (EEF1A1, DNAJA1, ZFX). No exonic variants were detected in any of the canine orthologues for human lumbar spinal stenosis candidate genes.

Conclusions: TTR (transthyretin) gene could be a possible candidate for lumbosacral stenosis in Labrador retrievers based on previous human studies that have reported an association between human lumbar spinal stenosis and transthyretin protein amyloidosis. Other genes identified with exonic variants in this study but with no known published association with lumbosacral stenosis and/or lumbar spinal stenosis could also be candidate genes for future canine lumbosacral stenosis studies but their roles remain currently unknown. Human lumbar spinal stenosis candidate genes also cannot be ruled out as lumbosacral stenosis candidate genes. More definitive genetic investigations of this condition are needed before any genetic test for lumbosacral stenosis in Labrador retriever can be developed.

Background: Genetic polymorphisms within the glutathione S-transferase P1 (GSTP1) gene affect the elimination of toxic xenobiotics by the GSTP1 enzyme. In dogs, exposure to environmental chemicals that may be GSTP1 substrates is associated with cancer. The objectives of this study were to investigate the genetic variability in the GSTP1 promoter in a diverse population of 278 purebred dogs, compare the incidence of any variants found between breeds, and predict their effects on gene expression. To provide information on ancestral alleles, a number of wolves, coyotes, and foxes were also sequenced.

Results: Fifteen single nucleotide polymorphisms (SNPs) and two microsatellites were discovered. Three of these loci were only polymorphic in dogs while three other SNPs were unique to wolves and coyotes. The major allele at c.-46 is T in dogs but is C in the wild canids. The c.-185 delT variant was unique to dogs. The microsatellite located in the 5' untranslated region (5'UTR) was a highly polymorphic GCC tandem repeat, consisting of simple and compound alleles that varied in size from 10 to 22-repeat units. The most common alleles consisted of 11, 16, and 17-repeats. The 11-repeat allele was found in 10% of dogs but not in the other canids. Unequal recombination and replication slippage between similar and distinct alleles may be the mechanism for the multiple microsatellites observed. Twenty-eight haplotypes were constructed in the dog, and an additional 8 were observed in wolves and coyotes. While the most common haplotype acrossbreeds was the wild-type *1A(17), other prevalent haplotypes included *3A(11) in Greyhounds, *6A(16) in Labrador Retrievers, *9A(16) in Golden Retrievers, and *8A(19) in Standard Poodles. Boxers and Siberian Huskies exhibited minimal haplotypic diversity. Compared to the simple 16*1 allele, the compound 16*2 allele (found in 12% of dogs) may interfere with transcription factor binding and/or the stability of the GSTP1 transcript.

Conclusions: Dogs and other canids exhibit extensive variation in the GSTP1 promoter. Genetic polymorphisms within distinct haplotypes prevalent in certain breeds can affect GSTP1 expression and carcinogen detoxification, and thus may be useful as genetic markers for cancer in dogs.