50 research outputs found
Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog
Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals
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The effect of inbreeding, body size and morphology on health in dog breeds
BackgroundDog breeds are known for their distinctive body shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized by distinct predispositions to disease. We explored the relationships between inbreeding, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity.ResultsThe average inbreeding based on genotype across 227 breeds was Fadj =β0.249 (95% CI 0.235-0.263). There were significant differences in morbidity between breeds with low and high inbreeding (Hβ=β16.49, P =β0.0004). There was also a significant difference in morbidity between brachycephalic breeds and non-brachycephalic breeds (P =β0.0048) and between functionally distinct groups of breeds (Hβ=β14.95 P <β0.0001). Morbidity was modeled using robust regression analysis and both body weight (P <β0.0001) and inbreeding (P =β0.013) were significant (r2 =β0.77). Smaller less inbred breeds were healthier than larger more inbred breeds.ConclusionsIn this study, body size and inbreeding along with deleterious morphologies contributed to increases in necessary health care in dogs
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DNA Sequence Variants in the Five Prime Untranslated Region of the Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves.
The aim of this study was to investigate the frequency of regional DNA variants upstream to the translation initiation site of the canine Cyclooxygenase-2 (Cox-2) gene in healthy dogs. Cox-2 plays a role in various disease conditions such as acute and chronic inflammation, osteoarthritis and malignancy. A role for Cox-2 DNA variants in genetic predisposition to canine renal dysplasia has been proposed and dog breeders have been encouraged to select against these DNA variants. We sequenced 272-422 bases in 152 dogs unaffected by renal dysplasia and found 19 different haplotypes including 11 genetic variants which had not been described previously. We genotyped 7 gray wolves to ascertain the wildtype variant and found that the wolves we analyzed had predominantly the second most common DNA variant found in dogs. Our results demonstrate an elevated level of regional polymorphism that appears to be a feature of healthy domesticated dogs
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Correction: DNA Sequence Variants in the Five Prime Untranslated Region of the Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves.
[This corrects the article DOI: 10.1371/journal.pone.0133127.]