BackgroundMeasurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor.ObjectiveTo investigate breed variation in plasma concentrations of pro‐atrial natriuretic peptide 31‐67 (proANP 31‐67) and N‐terminal B‐type natriuretic peptide (NT‐proBNP) in healthy dogs.Animals535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project.MethodsAbsence of cardiovascular disease or other clinically relevant organ‐related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31‐67 and NT‐proBNP were measured by commercially available ELISA assays.ResultsOverall significant breed differences were found in proANP 31‐67 (P < .0001) and NT‐proBNP (P < .0001) concentrations. Pair‐wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31‐67 as well as NT‐proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT‐proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT‐proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31‐67 concentrations, twice the median concentration in Doberman Pinschers.Conclusions and Clinical ImportanceConsiderable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT‐proBNP. Additional studies are needed to establish breed‐specific reference ranges.

Understanding the adaptive significance of multiple mating (polyandry) by females has long been a challenge in evolutionary biology. Several genetic and nongenetic benefits have been proposed to explain the evolution and maintenance of polyandry. In eusocial Hymenoptera, a prominent hypothesis is that increased genetic diversity within colonies results in more polymorphic workers and facilitates division of labour. We analysed the genetic basis of worker size (i.e. worker head width) and task preference in Cataglyphis cursor, an ant showing natural variations in queen-mating frequency. Our data show that increased genetic diversity within colonies does not result in more polymorphic workers. Moreover, worker head width is not different between patrilines within colonies. Consistent with these findings, worker size has a low heritable component. Moreover, task performance is not correlated with patriline. By contrast, it is significantly associated with worker size: the first foragers leaving the nest at sunrise are significantly larger than workers remaining in the nest. Overall, these results do not support the hypothesis that multiple mating is favoured because increased genetic diversity within colonies translates into more polymorphic workers and facilitates genetic polyethism. We discuss other hypotheses to account for the evolution of polyandry in C. cursor.

Results of this study reveal that Alternaria and Cladosporium species are part of the canine nasal flora, and that these fungi are probably not involved in the pathogenesis of lymphoplasmacytic rhinitis.

Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.

The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1-47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8-78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine. The domestic dogs share many diseases and phenotypes with human 1. Through two bottlenecks resulting from domestication 2 and the frequent use of specific males, each dog breed shows lower heterogeneity for disease. In humans, higher heterogeneity, meaning multiple variants with different levels of effects influencing the same disease, makes it difficult to identify genetic variants associated with disease 3. Therefore, dogs are considered an ideal model animal for identifying genes and genomic loci underlying diseases and phenotypic variation 1,4. Genome-wide association studies (GWAS) using canine single nucleotide polymorphism (SNP) chips have identified susceptibility genes and genomic loci for several complex diseases 5-10 and for many Mendelian disorders 11-16. The diagnosis of a disease often involves taking many clinical measurements including blood and urine analysis. These measurements directly reflect different aspects of the health of each individual. Individual differences in these measurements are known to be heritable in humans, and GWAS have identified genetic loci explaining these individual differences 17. A systematic analysis of 6,046 dogs has identified breed-specific differences in hematological measurements 18 , suggesting also a genetic contribution to the inter-breed variation for these

BackgroundPrimary ciliary dyskinesia (PCD) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene (CCDC39) has been identified in the Old English Sheepdog (OES).ObjectivesTo describe the clinical findings and the molecular changes of affected dogs and estimate the worldwide prevalence of the mutation in a large cohort of OES.Animals578 OES, including 28 affected and 550 clinically healthy dogs.MethodsThis retrospective study reviewed the data of OES diagnosed with PCD and OES tested for the mutation. Clinical data including results of physical examination and further investigations were obtained on 11/28 dogs. CCDC39 expression was assessed by qRT‐PCR and Western blot analysis in affected dogs and healthy dogs. DNA was extracted on 561/578 dogs and a genetic test by Taqman technology was developed to genotype the CCDC39 mutation in these dogs.ResultsClinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia. Ultrastructural defects were characterized by central microtubular abnormalities and decreased number of inner dynein arms (IDAs). Molecular analysis revealed a reduced expression of CCDC39 RNA and an absence of CCDC39 protein in affected dogs compared to healthy dogs. The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non‐European dogs (7%).Conclusion and Clinical Importance CCDC39 mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.

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