Summary The domestic dog serves as an excellent model to investigate the genetic basis of disease. More than 400 heritable traits analogous to human diseases have been described in dogs. To further canine medical genetics research, we established the Dog Biomedical Variant Database Consortium (DBVDC) and present a comprehensive list of functionally annotated genome variants that were identified with whole genome sequencing of 582 dogs from 126 breeds and eight wolves. The genomes used in the study have a minimum coverage of 10 × and an average coverage of ~24×. In total, we identified 23 133 692 single-nucleotide variants (SNVs) and 10 048 038 short indels, including 93% undescribed variants. On average, each individual dog genome carried ~ 4.1 million single-nucleotide and ~1.4 million short-indel variants with respect to the reference genome assembly. About 2% of the variants were located in coding regions of annotated genes and loci. Variant effect classification showed 247 141 SNVs and 99 562 short indels having moderate or high impact on 11 267 protein-coding genes. On average, each genome contained heterozygous loss-of-function variants in 30 potentially embryonic lethal genes and 97 genes associated with developmental disorders. More than 50 inherited disorders and traits have been unravelled using the DBVDC variant catalogue, enabling genetic testing for breeding and diagnostics. This resource of annotated variants and their corresponding genotype frequencies constitutes a highly useful tool for the identification of potential variants causative for rare inherited disorders in dogs.
Diabetes Mellitus (DM) is a syndrome caused by various etiologies. The clinical manifestations of DM are not indicative of the cause of the disease, but might be indicative of the stage and severity of the disease process. Accurately diagnosing and classifying diabetic dogs and cats by the underlying disease process is essential for current and future studies on early detection, prevention, and treatment of underlying disease. Here, we review the current etiology‐based classification of DM and definitions of DM types in human medicine and discuss key points on the pathogenesis of each DM type and prediabetes. We then review current evidence for application of this etiology‐based classification scheme in dogs and cats. In dogs, we emphasize the lack of consistent evidence for autoimmune DM (Type 1) and the possible importance of other DM types such as DM associated with exocrine pancreatic disease. While most dogs are first examined because of DM in an insulin‐dependent state, early and accurate diagnosis of the underlying disease process could change the long‐term outcome and allow some degree of insulin independence. In cats, we review the appropriateness of using the umbrella term of Type 2 DM and differentiating it from DM secondary to other endocrine disease like hypersomatotropism. This differentiation could have crucial implications on treatment and prognosis. We also discuss the challenges in defining and diagnosing prediabetes in cats.
Although most frog species are specialized for jumping or swimming, Kassina maculata (red-legged running frog) primarily uses a third type of locomotion during which the hindlimbs alternate. In the present study, we examined Kassina's distinct locomotory mode to determine whether these frogs walk or run and how their gait may change with speed. We used multiple methods to distinguish between terrestrial gaits: the existence or absence of an aerial phase, duty factor, relative footfall patterns and the mechanics of the animal's center of mass (COM). To measure kinematic and kinetic variables, we recorded digital video as the animals moved over a miniature force platform (N=12 individuals). With respect to footfall patterns, the frogs used a single gait and walked at all speeds examined. Duty factor always exceeded 0.59. Based on COM mechanics, however, the frogs used both walking and running gaits. At slower speeds, the fluctuations in the horizontal kinetic energy (Ek) and gravitational potential energy (Ep) of the COM were largely out of phase, indicating a vaulting or walking gait. In most of the trials, Kassina used a combined gait at intermediate speeds, unlike cursorial animals with distinct gait transitions. This combined gait, much like a mammalian gallop, exhibited the mechanics of both vaulting and bouncing gaits. At faster speeds, the Ek and Ep of Kassina's COM were more in phase, indicating the use of a bouncing or running gait. Depending on the definition used to distinguish between walking and running, Kassina either only used a walking gait at all speeds or used a walking gait at slower speeds but then switched to a running gait as speed increased.Movies available on-line.
The tauopathy-like phenotype observed in the rTg4510 mouse line, in which human tau P301L expression specifically within the forebrain can be temporally controlled, has largely been attributed to high overexpression of mutant human tau in the forebrain region. Unexpectedly, we found that in a different mouse line with a targeted-insertion of the same transgene driven by the same tetracycline-TransActivator (tTA) allele, but with even higher overexpression of tauP301L than rTg4510, atrophy and tau histopathology are delayed, and a different behavioral profile is observed. This suggests that it is not overexpression of mutant human tau alone that contributes to the phenotype in rTg4510 mice. Furthermore we show that the tauopathy-like phenotype seen in rTg4510 requires a ~70-copy tau-transgene insertion in a 244 kb deletion in Fgf14 , a ~7-copy tTA-transgene insertion in a 508 kb deletion that disrupts another five genes, in addition to high transgene overexpression. We propose that these additional effects need to be accounted for in any studies using rTg4510.
BackgroundHypercalciuria and hyperoxaluria are risk factors for calcium oxalate (CaOx) urolithiasis, but breed‐specific reports of urinary metabolites and their relationship with stone status are lacking.ObjectiveTo compare urinary metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations between CaOx stone formers and breed‐matched stone‐free controls for the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds.AnimalsForty‐seven Miniature Schnauzers (23 cases and 24 controls), 27 Bichons Frise (14 cases and 13 controls), and 15 Shih Tzus (7 cases and 8 controls).MethodsProspective study. Fasting spot urinary calcium‐to‐creatinine and oxalate‐to‐creatinine ratios (UCa/Cr and UOx/Cr, respectively) and blood iCa concentrations were measured and compared between cases and controls within and across breeds. Regression models were used to test the effect of patient and environmental factors on these variables.ResultsUCa/Cr was higher in cases than controls for each of the 3 breeds. In addition to stone status, being on a therapeutic food designed to prevent CaOx stone recurrence was associated with higher UCa/Cr. UOx/Cr did not differ between cases and controls for any of the breeds. Blood iCa was higher in cases than controls in the Miniature Schnauzer and Bichon Frise breeds and had a moderate correlation with UCa/Cr.Conclusions and Clinical ImportanceHypercalciuria is associated with CaOx stone status in the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. UOx/Cr did not correlate with stone status in these 3 breeds. These findings may influence breed‐specific stone prevention recommendations.
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