Canine medicine and genetics最新文献

Background: Discrete breed ideals are not restricted to delimiting dog breeds from another, but also are key drivers of subpopulation differentiation. As genetic differentiation due to population fragmentation results in increased rates of inbreeding and loss of genetic diversity, detecting and alleviating the reasons of population fragmentation can provide effective tools for the maintenance of healthy dog breeds.

Results: Using a genome-wide SNP array, we detected genetic differentiation to subpopulations in six breeds, Belgian Shepherd, English Greyhound, Finnish Lapphund, Italian Greyhound, Labrador Retriever and Shetland Sheepdog, either due to geographical isolation or as a result of differential breeding strategies. The subpopulation differentiation was strongest in show dog lineages.

Conclusions: Besides geographical differentiation caused by founder effect and lack of gene flow, selection on champion looks or restricted pedigrees is a strong driver of population fragmentation. Artificial barriers for gene flow between the different subpopulations should be recognized, their necessity evaluated critically and perhaps abolished in order to maintain genetic diversity within a breed. Subpopulation differentiation might also result in false positive signals in genome-wide association studies of different traits.

Lay summary: Purebred dogs are, by definition, reproductively isolated from other breeds. However, similar isolation can also occur within a breed due to conflicting breeder ideals and geographic distances between the dog populations. We show here that both of these examples can contribute to breed division, with subsequent loss of genetic variation in the resulting breed lineages. Breeders should avoid creating unnecessary boundaries between breed lineages and facilitate the exchange of dogs between countries.

Background: The calculation of demographic measures is a useful tool for evaluating the genomic architecture of dog breeds and enables ranking dog breeds in terms of genetic diversity. To achieve this for the German Dalmatian dog population, 307 purebred animals of this breed were genotyped on the Illumina Canine high density BeadChip. The analysis of pedigree-based inbreeding was performed based on a pedigree with 25,761 dogs including the genotyped dogs.

Results: The effective population size derived from squared correlation coefficients between SNP alleles (r ²) was 69. The maximum value of r ² was 0.56, resulting in a 50% decay value of 0.28 at a marker distance of 37.5 kb. The effective population size calculated from pedigree data using individual increase in inbreeding over equivalent generations was 116. The pedigree inbreeding coefficient was 0.026. The genomic inbreeding coefficient based on the length of runs of homozygosity (ROH) was calculated for seven length categories of ROHs, and ranged from 0.08 to 0.28. The fixation coefficients F_{IS_PED} and F_{IS_GENO} were at 0.017 and 0.004. PANTHER statistical overrepresentation analysis of genes located in consensus ROHs revealed highly underrepresented biological processes in 50% of the investigated dogs. One of those is the 0.28 fold enriched "immune response", which might be associated to the high prevalence of allergic dermatitis in the breed. Candidate genes for congenital sensorineural deafness (CCSD, a highly prevalent disease in the Dalmatian) were discovered in consensus ROHs.

Conclusions: The fast decay of r ² and the moderate inbreeding coefficients indicate that the German Dalmatian dog population is rather diverse. Pedigree- and genomic-based inbreeding measures were highly correlated and therefore prove good reliability for the given population. Analyses of consensus ROHs with genes coding for deafness and other breed-defining traits, such as hyperuricosuria, indicate that those ROH became fixed in the Dalmatian population about 500 years ago. In case of the Dalmatian dog, a ROH of 40 SNPs length is enough to investigate signatures of selection (e.g. the ROH with the fixed hyperuricosuria mutation) as far back as the breed formation point approximately 500 years ago.

Background: Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison's disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT).

Results: Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites.

Conclusions: This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.

Background: Conditions affecting the elbow joint are a common cause of lameness in dogs. Primary-care veterinary clinical data are now recognised as a valuable research resource. Using data from the VetCompass Programme, this study aimed to report the frequency and risk factors for elbow joint disease in dogs under primary veterinary care in the UK and describe clinical management.

Results: From 455,069 dogs under veterinary care, the one-year period prevalence for elbow joint disease diagnosis was 0.56% (95% CI: 0.53-0.60). Of 616 incident cases, the most common specific variants of elbow joint disease were osteoarthritis (n = 468, 75.97%), elbow dysplasia (190, 30.84%) and traumatic (41, 6.66%). The most common signs described by the owners were lameness (n = 466, 75.65%), difficulty exercising (123, 19.97%) and pain (86, 13.96%). The most common findings recorded on veterinary examination were pain (n = 283, 45.94%), lameness (278, 45.13%) and reduced range of movement (243, 39.45%). Common medications used included non-steroidal anti-inflammatory drugs (n = 544, 88.31%), tramadol (121, 19.64%) and disease modifying agents (118, 19.16%). Of 109 deaths involving euthanasia with information available from the 616 incident cases, elbow joint disease contributed to the decision to euthanase in 45 (41.28%) dogs.Five breeds showed increased odds of elbow joint disease compared with crossbred dogs: Rottweiler (OR: 6.16, 95% CI 3.89-9.75), Labrador Retriever (OR: 5.94, 95% CI 4.65-7.60), German Shepherd Dog (OR: 4.13, 95% CI 2.88-5.93), Golden Retriever (OR: 3.11, 95% CI 1.93-5.00) and English Springer Spaniel (OR: 2.00, 95% CI 1.26-3.18). Additional risk factors included having an adult bodyweight that was equal or higher than their breed/sex mean, advancing age, being male, being neutered, being insured and larger bodyweight.

Conclusions: Elbow joint disease is a relatively common diagnosis in dogs and has a high welfare impact as evidenced by the high proportion of cases recorded with pain, lameness and analgesic therapy. There are strong breed predispositions, in particular for large breed dogs. These findings present a clear case for improved breeding programmes to reduce the burden of elbow joint disease.