Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci.

BACKGROUND: Hip dysplasia and osteoarthritis continue to be prevalent problems in veterinary and human medicine. Canine hip dysplasia is particularly problematic as it massively affects several large-sized breeds and can cause a severe impairment of the quality of life. In Finland, the complex condition is categorized to five classes from normal to severe dysplasia, but the categorization includes several sub-traits: congruity of the joint, Norberg angle, subluxation degree of the joint, shape and depth of the acetabulum, and osteoarthritis. Hip dysplasia and osteoarthritis have been proposed to have separate genetic etiologies. RESULTS: Using Fédération Cynologique Internationale -standardized ventrodorsal radiographs, German shepherds were rigorously phenotyped for osteoarthritis, and for joint incongruity by Norberg angle and femoral head center position in relation to dorsal acetabular edge. The affected dogs were categorized into mild, moderate and severe dysplastic phenotypes using official hip scores. Three different genome-wide significant loci were uncovered. The strongest candidate genes for hip joint incongruity were noggin (NOG), a bone and joint developmental gene on chromosome 9, and nanos C2HC-type zinc finger 1 (NANOS1), a regulator of matrix metalloproteinase 14 (MMP14) on chromosome 28. Osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for NADPH oxidase 3 (NOX3), an intriguing candidate for articular cartilage degradation, and AT-rich interactive domain 1B (ARID1B) that has been previously linked to joint laxity. CONCLUSIONS: Our findings highlight the complexity of canine hip dysplasia phenotypes. In particular, the results of this study point to the potential involvement of specific and partially distinct loci and genes or pathways in the development of incongruity, mild dysplasia, moderate-to-severe dysplasia and osteoarthritis of canine hip joints. Further studies should unravel the unique and common mechanisms for the various sub-traits.

Provisional heritability estimates of four distraction index traits in a breeding population of German Shepherd dogs.

AIM To obtain provisional estimates of the heritability (h2 ) of passive laxity of the coxofemoral joints of a breeding colony of German Shepherd dogs, measured using the PennHIP distraction index (DI). METHODS Records were obtained of the PennHIP DI of right and left hips of 195 German Shepherd dogs (377 DI records) from the dog breeding colony of the New Zealand Police Dog Breeding Centre between 2003 and 2016, as well as pedigree records of 884 animals over four generations. Estimates of h2 and variance components for the log transformed DI data were obtained using restricted maximum likelihood procedures with a single trait sire model. Four DI traits for each dog were analysed: left hip, right hip, mean and worse-hip DI. The model included the fixed effects of sex and year of birth, with the age at scoring as a covariable, the random sire effect and residual error for each observation. RESULTS The h2 of the DI of the left hip (0.81, SE 0.40) was higher than the h2 of the DI of the right hip (0.35, SE 0.36). The h2 for the worse-hip DI (0.15, SE 0.28) in each dog was lower than the h2 of the individual hip DI, or the h2 for the mean of the two hips (0.53, SE 0.36) in each dog. The low number of generations prevented a meaningful analysis of the genetic trend. CONCLUSIONS AND CLINICAL RELEVANCE The h2 estimates for the left, right and mean DI traits were moderate to high, whereas the h2 estimates for the worse-hip DI (as used by the PennHIP programme for ranking of dogs) was low, but all estimates had large SE due to the small sample size. This provisional estimate of the h2 of four distraction index traits suggests that the mean DI could be useful as a selection tool against canine hip dysplasia in German Shepherd dogs, whereas the worse-hip DI may be less effective. Heritability estimates from a population with a greater number of DI measures is needed to validate this finding given the large SE in our study.

Common Orthopedic Traits and Screening for Breeding Programs.

Orthopedic diseases are complex traits, meaning genetics and environmental factors affect risk, making identification of genetic associations difficult. In the United States, hip and elbow scores, patellar luxation scores, Legg-Calvé-Perthes disease, and shoulder osteochondrosis affectedness are available in the Orthopedic Foundation for Animals registry. Distraction indices and extended, ventrodorsal hip conformation scores are recorded by PennHIP. Application of estimated breeding values for hip and elbow dysplasia in breeder selection reduces the severity and prevalence of these traits. Genomic prediction and whole-genome sequence technologies and methods should improve knowledge of genetics underlying orthopedic diseases, leading to improved canine orthopedic genetic quality.

Palpation and dorsal acetabular rim radiographic projection for early detection of canine hip dysplasia: a prospective study.

OBJECTIVE: To determine the value of 2 diagnostic methods: (1) the reduction angle (RA) using the Ortolani maneuver and (2) the dorsal acetabular slope (DAS) from the dorsal acetabular rim (DAR) radiographic projection, to predict osteoarthritis (OA) in dogs with hip dysplasia. STUDY DESIGN: Prospective study. SAMPLE POPULATION: Dogs (n = 73). METHODS: Hip-extended ventrodorsal (VD) radiographic projections, RA, and DAS were evaluated when dogs were 6, 12, and 24 months of age. VD projections were qualitatively scored for OA. RA was determined using the Ortolani maneuver in dorsal recumbency and DAS using the DAR projection. Distraction index (DI) measurements from the compression-distraction radiographic projections (PennHIP method) were also performed at 6 months of age. Statistical analyses were used to establish the range of values of normal and abnormal RA and DAS, to document the temporal variation in RA and DAS, to compare the ability of the different methods to predict coxofemoral OA, to determine the influence of pure passive laxity and of the DAS on the occurrence of an Ortolani sign and on the magnitude of the RA, to establish the relationship between the DAS and subsequent development of passive laxity and coxofemoral OA, and to evaluate the influence of the DAS and RA on the occurrence of coxofemoral OA with severe, moderate, and minimal coxofemoral passive joint laxity, respectively. RESULTS: VD, RA, DAS, and DI methods of coxofemoral joint evaluation correlated significantly with the status of the coxofemoral joints at 2 years of age. The risk of occurrence of coxofemoral OA increased, as the RA, DAS, or DI increased. There was a significant positive linear relationship between RA and DI (P = .015, r(2) = 0.32), RA and DAS (P = .0078, r(2) = 0.38), and DAS and DI (P = .015, r(2) = 0.33). A negative Ortolani sign was at all times significantly predictive of absence of coxofemoral OA at 2 years of age. DAS best predicted coxofemoral OA for DI ≥ 0.7, whereas RA best predicted coxofemoral OA for 0.3 < DI < 0.7; however, RA proved to be the best overall predictor of coxofemoral OA. CONCLUSION: RA measured at 6 months of age in dorsal recumbency was the best predictor of coxofemoral OA at 2 years of age.

Prime editor-mediated correction of a pathogenic mutation in purebred dogs.

Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part I: two year results of computed tomography and distraction index.

OBJECTIVES: To measure one and two year effects of juvenile pubic symphysiodesis (JPS) in puppies defined as 'at-risk' for canine hip dysplasia (CHD) using the following objective hip conformation criteria: Acetabular angle (AA), dorsal acetabular rim angle (DARA) and hip laxity (PennHIP© distraction index (DI). DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies (six controls). PROCEDURES: The dogs were anaesthetised and acetabular angle, DARA, and DI values were obtained by computed tomography and radiography preoperatively. Electro-cautery fusion of the pubic symphysis was performed between 12 - 24 weeks of age. The imaging was repeated at one and two years of age. RESULTS: Significant hip improvements were seen at the two-year follow-up appointments for: AA (JPS dogs 31% increase, control 3%), DARA (JPS 38% decrease, control 15%) and DI (JPS 41% decrease in laxity, controls 20%) for all postoperative versus preoperative values. Pubic fusion occurred with minor morbidity. CONCLUSION: Juvenile pubic symphysiodesis resulted in significant improvements in hip conformation (AA and DARA), especially in mild to moderately lax hips (DI = 0.40-0.69). Most dogs with DI≥0.70 increased in osteoarthritis grade by two years of age. CLINICAL RELEVANCE: Juvenile pubic symphysiodesis surgery at 12-24 weeks of age significantly improved hip conformation and decreased laxity in at-risk CHD dogs. Early-age (12 to 16 week) recognition of hip laxity offered greater JPS benefits than surgery performed at 19- to 24-weeks-old. Dogs with severe laxity (DI≥0.70) continued to increase in osteoarthritis. An early (12-16 weeks) positive laxity test (Ortolani) should alert one to obtain objective laxity determinations (PennHIP© DI).

Canine hip dysplasia screening: Comparison of early evaluation to final grading in 231 dogs with Fédération Cynologique Internationale A and B.

OBJECTIVES: This study aimed to verify if a significant difference exists between parameters in the early evaluation of normal and near-normal hip joints, to evaluate the influence of age and breed on the parameters, and to clarify the usefulness of a total score for differentiating between Fédération Cynologique Internationale (FCI) grade A and B hips. METHODS: A total of 231 dogs were classified according to whether they had FCI A or B hips at adulthood, with measurements obtained at 14-28 weeks of age. The total score was calculated by the summation of the following quantitative parameters: angle of subluxation (AS), angle of reduction (AR), laxity index (LI), and dorsal acetabular rim slope (DARS). Logistic regression analysis was performed to establish the probability of the study population to develop an FCI B hip based on the total score. This was repeated for the highest score in combination with the worst-rated hip and once more for breeds. RESULTS: No correlation between age and the parameters was found in the cohort, or for FCI A and B. The values of all the parameters were significantly lower in the FCI A group than in the FCI B group (AR: 4.42° ± 6.0° vs 7.62° ± 7.2°; AS: 0.45° ± 1.9° vs 1.55° ± 3.8°; LI: 0.32 ± 0.1 vs 0.36 ± 0.1; DARS: 3.30° ± 1.8° vs 3.77° ± 1.9°; TS: 11.47 ± 8.3 vs 16.65 ± 10.9). Labrador Retrievers and Golden Retrievers showed significant differences between parameters for both FCI grades. The range, where FCI A and B hips can be predicted on the basis of the total score, was different when assessed for the entire cohort, Labrador Retrievers, and Golden Retrievers. CLINICAL SIGNIFICANCE: Our results show that even in normal and near-normal hips, the parameters significantly differed in the early evaluation. Moreover, cutoff values should be set for different breeds in the prediction of the FCI grade during early evaluation for a better breeding selection regarding canine hip dysplasia, one of the most common orthopedic diseases among large and giant breed dogs.

The differentiating ability of four plasma biomarkers in canine hip dysplasia.

BACKGROUND: The accumulation of cartilage breakdown products in body fluids has been extensively investigated to assess the accuracy of molecular biomarkers from a diagnostic, prognostic, and therapeutic perspective. Nevertheless, to the authors' knowledge, there is a lack of information about spontaneous models of hip osteoarthritis and the differentiating ability of collagen, noncollagen, and inflammatory biomarkers. OBJECTIVES: We aimed to assess the accuracy of four plasma biomarkers that could differentiate between healthy dogs and dogs with hip dysplasia. METHODS: Twenty-four dogs were used in this institutionally approved study (12 in the mild to severe hip dysplasia group; 12 in the control group). Plasma concentrations of biomarkers were compared. The ability of each marker to differentiate control from diseased dogs was assessed using an independent t-test, logistic regression, and receiving operating characteristics (ROC) analysis. RESULTS: Three biomarkers were significantly different between the two groups. The collagen marker procollagen type II propeptide (PIICP) was useful in differentiating between control and diseased dogs with the best combination of sensitivity and specificity. The four biomarkers showed high area under the curve (AUC) values. CONCLUSIONS: The results indicate that plasma biomarkers can be used as a screening tool for canine hip dysplasia. Although the cutoff values and diagnostic ability of the biomarkers used in this study show promising results, the sources of individual variability should be addressed. Future studies with larger groups of dogs are needed to correlate plasma levels in serum and synovial fluid during clinical disease.

Early hip laxity examination in predicting moderate and severe hip dysplasia in Estrela mountain dog.

OBJECTIVES: To determine the reliability of early passive hip laxity examination in predicting moderate and severe hip dysplasia. METHODS: The passive hip laxity of 104 Estrela Mountain dogs was evaluated using the Ortolani method, conventional hip-extended radiography and the PennHIP method, when the animals were between four and 12 months of age. After the age of one, dogs were re-examined for hip dysplasia using the Fédération Cynologique Internationale scoring system. The passive hip laxity results were subsequently compared with the Fédération Cynologique Internationale scores for sensitivity, specificity, positive predictive value, negative predictive value and accuracy. RESULTS: The PennHIP method achieved the best results in specificity (93 per cent), positive predictive value (91 per cent) and accuracy (88 per cent), and the Ortolani method was the best in sensitivity (92 per cent) and negative predictive value (92 per cent). CLINICAL SIGNIFICANCE: The Fédération Cynologique Internationale grades D and E can be predicted with confidence even before animals are one year old.

Radiographic findings in the coxofemoral joint of Australian Cattle Dogs / Achados radiográficos em articulação coxofemoral de cães da raça Australian Cattle Dog

Australian Cattle Dogs (ACD) are medium-sized animals widely used in fieldwork for managing cattle and sheep. There needs to be more information about the conditions these dogs can develop despite being well-characterized animals since the beginning of the 20th century. Hip dysplasia (HD) is a developmental abnormality between the femoral head and the acetabular fossa, which can be debilitating. However, the available literature has no studies on the prevalence of this condition in dogs of this breed. This study aimed to evaluate radiographs of ACD qualitatively and quantitatively. For this purpose, 49 dogs considered healthy without clinical signs of HD were radiographically assessed, and the animals were classified as dysplastic (D) and non-dysplastic (ND). A frequency of 46.9% of dysplastic dogs was observed, with males being more affected. The cortical index (CI) and angle of inclination (AI) could not differentiate D from ND animals; only the Norberg angle (NA) was effective in this differentiation. No correlation was observed between AI, CI, and AN.(AU)

Os cães da raça Autralian Cattle Dog (ACD) são animais de porte médio, muito utilizados no trabalho de campo para manejo de gado e ovelha. Apesar de serem animais bem caracterizados desde o início do século XX, há poucas informações sobre afecções que esses cães podem desenvolver. A displasia coxofemoral (DCF) é uma anormalidade do desenvolvimento entre a cabeça do fêmur e a fossa acetabular podendo ser debilitante. Contudo, não há estudos, na literatura disponível, sobre a prevalência desta afecção em cães dessa raça. O objetivo deste trabalho foi avaliar qualitativamente e quantitativamente radiografias de cães da raça ACD. Para tanto, foram avaliados radiograficamente 49 cães considerados hígidos e sem sinais clínicos de DCF. Os animais foram classificados em displásicos (D) e não displásicos (ND). Observou-se a frequência de 46,9% de cães displásicos, sendo os machos mais acometidos. O índice cortical (IC) e o ângulo de inclinação (AI) não foram capazes de diferenciar os animais D dos ND, apenas o ângulo de Norberg (AN) foi eficaz nessa diferenciação. Não houve correlação entre AI, IC e AN.(AU)

Impact of sedation method on the diagnosis of hip and elbow dysplasia in Swedish dogs.

Our objective was to investigate the effect of sedation method on the screening result for hip and elbow dysplasia. The study was based on a questionnaire survey of routines for hip and elbow screening at Swedish veterinary clinics and results of hip and elbow status, for eight breeds (Bernese Mountain Dog, Boxer, German Shepherd Dog, Golden Retriever, Labrador Retriever, Newfoundland, Rottweiler, and Saint Bernard) recorded by the Swedish Kennel Club. In total 5877 and 5406 dogs examined for hip and elbow dysplasia, respectively, from January 2002 through March 2003 were included. We used logistic regression to examine whether the type of chemical restraint used for sedation affected the screening result for hip and elbow dysplasia. In addition to sedation method, the effects of veterinary clinic, sex, breed, and age at screening were studied. The type of chemical restraint used for sedation affected the screening result for hip but not for elbow dysplasia. Acepromazine gave less than half the odds of hip dysplasia compared with medetomidine and butorphanol (the most common method), medetomidine alone or xylazine. Females had about 25% higher odds for developing hip dysplasia whereas males had almost 40% higher odds for developing elbow dysplasia. Saint Bernard, Newfoundland and German Shepherd Dog had the highest odds of developing hip dysplasia, whereas Rottweiler and Labrador Retriever had the lowest odds. Boxer had the lowest risk for elbow dysplasia, followed by Labrador Retriever. Saint Bernard and Rottweiler had the highest odds of elbow dysplasia. Increasing age increased the odds of both hip and elbow dysplasia, by about 2.5% per month. Following the results in this study, recording of the type of chemical restraint used for sedation during hip screening has now become mandatory in Sweden. This makes it possible to account for the effect of sedation method in a model for prediction of breeding values for hip dysplasia.

Measurement of the femoral neck anteversion angle in the dog using computed tomography.

Simple and accurate limb and pelvic conformation evaluation using computed tomography (CT) can be useful in planning canine hip dysplasia (CHD) treatment and in helping to understand the pathogenesis of osteoarthritis and CHD. The objectives of this study were to describe a new method for femoral neck anteversion angle (FNA-angle) measurement in CT, and to compare it to the established radiographic standard biplanar method. The hips of 23 Estrela Mountain Dogs were evaluated using radiography and CT and their FNA-angles were determined by performing two CT examinations and with one radiographic measurement session. The intra-class correlation coefficient (ICC) was used to evaluate the repeatability (agreement between the two CT sessions, ICC=0.92) and reproducibility (agreement between each CT and radiographic session, ICC=0.91 in both cases) of the CT FNA-angle measurement method. This study suggests that CT FNA-angle measurement method is reliable and can be used in CT hip studies with confidence.

Assessment of the hip reduction angle for predicting osteoarthritis of the hip in the Labrador Retriever.

Hip palpation has been used to provide semiquantitative information regarding passive joint laxity and susceptibility to hip dysplasia. The purpose of this study was to: (1) evaluate the intra- and inter-examiner repeatability of the hip reduction angle measured at 4 months of age by three examiners using manual goniometry and an electromagnetic tracking system; (2) compare the hip reduction angle measured with manual goniometry to the hip reduction angle measured with the electromagnetic tracking system; and (3) evaluate the hip reduction angle, distraction index and Ortolani manoeuvre at 4 months of age as predictors of the development of hip osteoarthritis at 12 months of age in 11 Labrador Retriever dogs. Intra- and inter-examiner repeatability was demonstrated for both the manual and electromagnetic goniometric measurement of the hip reduction angle (coefficient of variation < 4.3% and < 6.1%; and P = 0.163 and P = 0.836 respectively). The hip reduction angle measured by manual goniometry was moderately correlated to the hip reduction angle measured by the electromagnetic tracking system (r = 0.603, P < 0.0000). The hip reduction angle measured by manual and electromagnetic goniometry was a poor predictor of osteoarthritis at 12 months of age (r = 0.231, P < 0.062, and r = 0.321, P < 0.01). The distraction index was moderately correlated with the development of osteoarthritis by 12 months of age (r = 0.493, P < 0.0000). The Ortolani sign was sensitive (100%) but not specific (41%) for the development of osteoarthritis at 12 months of age. The hip reduction angle did not further quantify the Ortolani manoeuvre as a predictor of osteoarthritis in Labrador Retrievers.

Mechanical devices to help in PennHIP examination.

A modified PennHIP procedure (MPP), using specific mechanical holding devices, was used on 70 dogs and compared to the standard PennHIP method (SPM) used on 39 dogs, in terms of technical effectiveness and the mean number of essential individuals within the X-ray room (EIXRR). The data using the Chi-squared test were consistent with the null hypothesis that the technical effectiveness was equal in the groups under investigation (P > 0.05). On the contrary, using the two-sample unpaired t-test the null hypothesis, that the mean EIXRR was equal, was rejected (P < 0.001). The estimated EIXRR was 3.4 +/- 0.7 and 5.7 +/- 1.2 (mean +/- SD) for MPP and SPM, respectively. In conclusion, the MPP needs fewer EIXXR than the SPM and complies with the new recommendations in X-ray protection, which introduce the ALARA (as-low-as-reasonably-achievable) idea.

Genetic correlations of hip dysplasia scores for Golden retrievers and Labrador retrievers in France, Sweden and the UK.

In order to reduce the prevalence of inherited diseases in pedigree dogs, the feasibility of implementation of an international breeding program was investigated. One prerequisite is a strong genetic correlation between countries and our objective was to estimate this correlation for canine hip dysplasia (HD) across three countries to evaluate the feasibility of an international genetic evaluation. Data were provided by the Société Centrale Canine (SCC, France), Svenska Kennelklubben (SKK, Sweden) and The Kennel Club (KC, UK) on Golden retriever and Labrador retriever dogs. Trivariate analysis on the three different modes of scoring HD in France, Sweden and the UK was performed using a mixed linear animal model. Heritability, genetic correlation, number of common sires, genetic similarity, selection differentials and accuracy of selection were calculated. The estimated heritabilities of Golden retrievers (Labrador retrievers) for HD scores were 0.28 (0.15), 0.28 (0.29) and 0.41 (0.34) in France, Sweden and the UK, respectively. The feasibility of performing a genetic evaluation of HD across countries was indicated by the favourable genetic correlations estimated between score modes (ranged from 0.48 to 0.99). The accuracy of selection for the most recent birth year cohorts of male dogs was not improved by international evaluation compared to national evaluation. Improvement in genetic progress can however be achieved by selection across populations in different countries, particularly for small populations, which were indicated by the large difference between selection differentials based on the national and international evaluations.

Inter-rater agreement in radiographic canine hip dysplasia evaluation.

The objective was to determine the agreement between scrutineers assessing canine hip dysplasia (CHD) within and between the Fédération Cynologique Internationale (FCI) and the Swiss (CH) grading schemes, and between first-opinion and second-opinion scrutineers using the CH scheme. 62 scrutineers, participating in a quality assessment programme, were asked to evaluate 12 sets of hip radiographs. All radiographs had been previously evaluated by a first-opinion and 7 by both a first-opinion and second-opinion scrutineers using the CH scheme. Inter-rater agreement (κ) and intraclass correlation (ICC) were evaluated for the Norberg angle and dysplasia grades, and ICC for the numerical CH scores. The κ and ICC were 0.290 and 0.471 for Norberg angles, 0.372 and 0.577 for FCI grades, and 0.417 and 0.567 for CH grades, respectively. The ICC for CH scores was 0.614. Total agreement for grades was found in a single case. For radiographs evaluated using both schemes, raters gave the same grade in 441 cases, a lower FCI than CH grade in 78 cases and a lower CH than FCI grade in 32 cases. Intrarater agreement between grades of the two schemes was 0.786. Agreement between the first-opinion and second-opinion scrutineers was 0.250 for Norberg angles and -0.286 for CH grades. Although agreement between the two schemes was good, agreement between scrutineers using either scheme was only fair to moderate, and no agreement was found between first-opinion and second-opinion scrutineers. Application of the FCI and CH schemes may impact the incidence of hip dysplasia in populations with both severe and moderate dysplasia, but is unlikely to impact populations with only mild dysplasia. The CH system of first-opinion and second-opinion examinations should be re-evaluated.

Hip Dysplasia: Clinical Signs and Physical Examination Findings.

Hip dysplasia is a common developmental disorder of the dog, consisting of varying degrees of hip laxity, progressive remodeling of the structures of the hip, and subsequent development of osteoarthritis. It is a juvenile-onset condition, with clinical signs often first evident at 4 to 12 months of age. A tentative diagnosis of hip dysplasia can be made based on signalment, history, and physical examination findings. The Ortolani test is a valuable tool for identifying juvenile dogs affected with this condition. Further diagnostics can then be prioritized, contributing to prompt diagnosis and appropriate treatment.

Prospective evaluation of a patented DNA test for canine hip dysplasia (CHD).

Genetic testing has been propagated as a suitable means to specify individual risks for canine hip dysplasia (CHD). However, the current lack of validation of most genetic CHD tests has left dog owners and breeders in the dark about their practical utility. Therefore, the Society for German Shepherd Dogs (Verein für Deutsche Schäferhunde, SV) initiated a prospective study of 935 animals to assess independently the value of a genetic CHD test (European Patent Specification EP 2 123 777 B1) that was developed by Distl et al. (2009) on the basis of the SV animal stock. Dogs were followed-up for 3 years after birth, classified regarding their CHD phenotype using the scheme of the Fédération Cynologique Internationale, and genotyped for the 17 single nucleotide polymorphisms (SNPs) constituting the CHD test in question. Individual SNP genotypes were combined into animal-specific genomic breeding values (GBVs), calculated as the weighted sum of SNP-wise scores as laid down in the patent specification. Logistic regression analysis revealed that, unexpectedly, the odds ratio for CHD decreased, rather than increased, by a factor of 0.98 per unit increase of the GBV. Nevertheless, since this effect was not statistically significant (95% CI: 0.93-1.03), and the area-under-curve of the test was only 0.523, it must be concluded that the genetic test patented by Distl et al. (2009) is unsuitable for individual CHD risk assessment.

Repeatability and reproducibility of distraction indices in PennHIP examinations of the hip joint in dogs.

Repeatability and reproducibility of Distraction Index (DI) measurements in the PennHIP method were evaluated in 100 dogs. The PennHIP distraction views sent to the PennHIP Analysis Center (PAC) were duplicated, digitalised, and identified with a code, and an adequate computer software was used for DI measurements. One examiner performed two DI measurement sessions, evaluating individually 200 hip joints. The scoring repeatability and reproducibility were estimated calculating the Intraclass Correlation Coefficient (ICC) between the two DI measurement sessions and between the second DI measurement session and the DI in PAC reports, respectively. The ICC for repeatability was 0.97 [95% confidence interval (CI), 0.96 to 0.98], and the ICC for reproducibility was 0.95 (95% CI, 0.93 to 0.96). The results suggest that the DI measurement method described is repeatable and can reproduce the PAC reports with confidence. Distraction indices measured in different PennHIP studies, using this DI measurement method and performed by trained researchers, can be considered interchangeable.