Correction: The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels.

[This corrects the article DOI: 10.1371/journal.pgen.1009726.].

The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels.

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heart-derived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.

Robenacoxib versus meloxicam for the management of pain and inflammation associated with soft tissue surgery in dogs: a randomized, non-inferiority clinical trial.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a new NSAID with high selectivity for the cyclo-oxygenase (COX)-2 isoform of COX. The objective of this study was to evaluate the efficacy and tolerability of robenacoxib for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs. The study was a prospective, randomized, blinded, positive-controlled, non-inferiority, multi-center clinical trial. A total of 174 dogs undergoing major soft tissue surgery were included and randomly allocated in a 2:1 ratio to receive either robenacoxib (n = 118) or the positive control, meloxicam (n = 56). Each dog received an initial dose subcutaneously prior to surgery (robenacoxib 2 mg/kg, meloxicam 0.2 mg/kg), followed by daily oral doses (robenacoxib 1-2 mg/kg, meloxicam 0.1 mg/kg) for 12 days (range 10-14) after surgery. Pain and inflammation were assessed subjectively using the Glasgow Composite Pain Scale (GCPS) by clinicians as the primary end point and additional evaluations by the clinicians and animal owners as secondary endpoints. RESULTS: Both treatments provided similar pain control, with no significant differences between groups for any efficacy variable using non-parametric analyses (Mann-Whitney U test). In no dog was analgesic rescue therapy administered. Non-inferior efficacy of robenacoxib compared to meloxicam was demonstrated statistically for the primary and all secondary endpoints using parametric analysis of variance, although the data were not normally distributed even after log transformation. For the primary endpoint (reciprocal of the modified GCPS score), the relative efficacy of robenacoxib/meloxicam was 1.12 with a 95% confidence interval of 0.97-1.29. CONCLUSION: A treatment regimen of robenacoxib by subcutaneous injection followed by oral tablets had good tolerability and non-inferior efficacy compared to meloxicam for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs.

Evaluation of subcutaneous and oral administration of robenacoxib and meloxicam for the treatment of acute pain and inflammation associated with orthopedic surgery in dogs.

OBJECTIVE: To assess efficacy and tolerability of robenacoxib for control of pain and inflammation in dogs undergoing orthopedic surgery. ANIMALS: 140 client-owned dogs. PROCEDURES: A multicenter, prospective, randomized, blinded field trial was conducted to compare robenacoxib (97 dogs) and meloxicam (43 dogs). After randomization, each dog received an initial dose (robenacoxib, 2 mg/kg; meloxicam, 0.2 mg/kg) via SC injection before surgery and daily doses (robenacoxib, 1 to 2 mg/kg; meloxicam, 0.1 mg/kg) administered orally for up to 15 days after surgery. Efficacy was assessed by veterinarians and owners via numeric rating scales and visual analogue scales. Safety was assessed on the basis of reported adverse events, clinical signs, results of hematologic and biochemical analyses, and buccal mucosa bleeding times. RESULTS: Treatment groups were balanced with respect to baseline and demographic data. Both treatments provided similar adequate pain control, as assessed with a modified Glasgow pain scale as the primary end point and supported by secondary end points in evaluations conducted by veterinarians and owners. For the primary end point, the ratio of the reciprocal of the scores for robenacoxib to meloxicam was 1.16 (95% confidence interval, 0.98 to 1.37). No dogs required rescue analgesia. Both treatments were associated with only minor adverse events, which were not necessarily related to the administered treatments and did not affect mucosal bleeding times. CONCLUSIONS AND CLINICAL RELEVANCE: Robenacoxib provided efficacy and tolerability similar to those of meloxicam for the management of perioperative pain and inflammation in dogs undergoing orthopedic surgery.