ABSTRACT
The dog leukocyte antigen (DLA) system contains many of the functional genes of the immune system, thereby making it a candidate region for involvement in immune-mediated disorders. A number of studies have identified associations between specific DLA class II haplotypes and canine immune hemolytic anemia, thyroiditis, immune polyarthritis, type I diabetes mellitus, hypoadrenocorticism, systemic lupus erythematosus-related disease complex, necrotizing meningoencephalitis (NME) and anal furunculosis. These studies have relied on sequencing approximately 300 bases of exon 2 of each of the DLA class II genes: DLA-DRB1, DLA-DQA1 and DLA-DQB1. In the present study, an association (odds ratio=4.29) was identified by this method between Weimaraner dogs with hypertrophic osteodystrophy (HOD) and DLA-DRB1∗01501. To fine map the association with HOD, a genotyping assay of 126 coding single nucleotide polymorphisms (SNPs) from across the entire DLA, spanning a region of 2.5 Mb (3,320,000-5,830,000) on CFA12, was developed and tested on Weimaraners with HOD, as well as two additional breeds with diseases associated with DLA class II: Nova Scotia duck tolling retrievers with hypoadrenocorticism and Pug dogs with NME. No significant associations were found between Weimaraners with HOD or Nova Scotia duck tolling retrievers with hypoadrenocorticism and SNPs spanning the DLA region. In contrast, significant associations were found with NME in Pug dogs, although the associated region extended beyond the class II genes. By including a larger number of genes from a larger genomic region, a SNP genotyping assay was generated that provides coverage of the extended DLA region and may be useful in identifying and fine mapping DLA associations in dogs.
Subject(s)
Addison Disease/veterinary , Bone Diseases, Metabolic/veterinary , Dog Diseases/genetics , Genotyping Techniques/methods , Histocompatibility Antigens Class II/genetics , Meningoencephalitis/veterinary , Addison Disease/genetics , Addison Disease/immunology , Animals , Bone Diseases, Metabolic/genetics , Bone Diseases, Metabolic/immunology , Dog Diseases/immunology , Dogs , Exons , Genes, MHC Class II , Genetic Predisposition to Disease , Genome-Wide Association Study/veterinary , Haplotypes , Histocompatibility Antigens Class II/immunology , Meningoencephalitis/genetics , Meningoencephalitis/immunology , Odds Ratio , Pedigree , Polymorphism, Single Nucleotide , Species SpecificityABSTRACT
Hyperuricosuria, an autosomal recessive disorder, is characterized by high levels of uric acid in the urine of Dalmatian dogs. Whereas high levels of uric acid are known to be caused by the silencing of the urate oxidase (uox) gene in humans and higher primates, the molecular basis for the Dalmatian defect is unknown. Transplantation studies show that the organ responsible for the Dalmatian phenotype is the liver, which is where urate oxidase is exclusively expressed and uric acid is converted into allantoin. We cloned and sequenced the canine uox cDNA and compared the sequence between a Dalmatian and non-Dalmatian dog. No change in cDNA sequence was identified. A Dalmatian x pointer backcross family was used to track the segregation of microsatellite markers surrounding the urate oxidase locus. The uox gene was excluded for Dalmatian hyperuricosuria based on the cDNA sequence identity and negative LOD scores.
Subject(s)
Dog Diseases/genetics , Urate Oxidase/genetics , Uric Acid/urine , Animals , Base Sequence , Cloning, Molecular , DNA, Complementary/chemistry , Dogs , Genotype , Inbreeding , Lod Score , Male , Mice , Microsatellite Repeats/genetics , Molecular Sequence Data , Papio , Sequence Analysis, DNA , SwineABSTRACT
Two different vaccination protocols were compared with regard to the development of hypertrophic osteodystrophy (HOD) (also termed metaphyseal osteopathy) and effectiveness of immunisation in a litter of 10 Weimaraner puppies. Five puppies (group 1) were vaccinated with a modified live canine parvovirus vaccine (CPV) and then two weeks later with a trivalent vaccine containing modified live canine distemper virus and adenovirus type 2 combined with a Leptospira bacterin (DHL). The CPV and DHL vaccine protocols were administered a further two times, at two-week intervals. Group 2 was vaccinated with three consecutive multivalent vaccines containing modified live canine distemper virus, canine parvovirus, parainfluenza and adenovirus type 2 combined with a Leptospira bacterin, at four-week intervals. All puppies were first vaccinated at the age of eight weeks. Three dogs in group 1 developed HOD, while all five dogs in group 2 developed HOD during the study period. Dogs in group 2 had more episodes of HOD than those in group 1. Dogs in group 1 developed higher antibody titres to canine distemper virus and parvovirus compared with those in group 2. Only two out of the 10 dogs developed protective antibody titres to parvovirus. The results of this study suggest that the two different vaccination protocols affected the pattern of appearance of HOD and immunisation in this litter of Weimaraner puppies. The results obtained and the previously reported data suggest that a larger controlled study is needed to further elucidate the effect of different vaccination protocols on HOD and immunisation in Weimaraner puppies.