An epidemiological approach to prevention and control of three common heritable diseases in canine pedigree breeds in the United Kingdom.

This paper reviews recent epidemiological research in the United Kingdom for controlling deafness in Dalmatians, glaucoma in flat coated retrievers and great Danes and hip dysplasia in flat coated retrievers, Newfoundlands, Gordon setters and Labrador retrievers. These studies assessed the prevalence of the disease, identified the factors affecting prevalence, and developed predictive statistical models of offspring/parent relationships. For each disease/breed combination, the research identified those sires and dams that might justifiably be regarded as suitable/unsuitable as potential parents in a selective breeding strategy to control or prevent the disease. Future progress in the control of these diseases is likely to come from greater understanding of their mode of inheritance. Insight, even for these complex diseases, can be derived from further detailed statistical evaluation of datasets such as those described in this paper.

Effect of month of birth on hip dysplasia in labrador retrievers and Gordon setters.

Recent studies have proposed selective breeding policies for preventing or controlling hip dysplasia, based upon the relationships between the hip scores of the offspring and their parents. However, these studies have ignored the possible effects on an animal's hip score of its age when it was examined and the month in which it was born. This paper describes the results of statistical analyses of large data sets of Kennel Club-registered labrador retrievers and Gordon setters. Regression modelling showed that an animal's hip score depended significantly upon the hip score of its sire and dam, and upon its month of birth. Enlarging the model by including its age when examined made it possible to quantify the significant genetic parental effects and the effects of the animal's month of birth and its age when examined.

Hip dysplasia in labrador retrievers: the effects of age at scoring.

Selective breeding policies for preventing or controlling hip dysplasia require accurate estimates of parameters in offspring/parental relationships and estimates of heritability. Recent literature includes some major studies of pedigree breeds of dog, using data derived from the hip dysplasia screening scheme set up by the British Veterinary Association. These publications have not taken into account the age of the animals when they were screened. This study analyses the data from 29,213 labrador retrievers whose ages were known when they screened. The mean hip score of the dogs was positively and significantly correlated with their age. If this relationship with age is ignored, various offspring/parental relationships and the estimates of heritability are likely to be distorted.

Heritability and epidemiology of canine hip-dysplasia score and its components in Labrador retrievers in the United Kingdom.

Hip-dysplasia (malformation of the coxofemoral joint) in dogs is a major health problem. Under the British Veterinary Association/Kennel Club's voluntary hip-dysplasia scheme, dog-owners/breeders submit radiographs from animals >1-year-old, to ensure adequate skeletal maturity. An overall hip score quantifies the degree of malformation in the hip joints of these animals, by summing the scores for nine components of the radiographs of both the left and right joints. The hip score data for 29,610 Labrador retrievers (registered with The Kennel Club, UK) were merged with the Kennel Club pedigree database for 472,435 Labrador retrievers. The merged data included the animal's identity, date of birth, sex and hip score and similar records for the dog's relatives, including the hip score if the relative had been tested. In recent years, breeding had been increasingly from tested parents. The mean hip score for male Labradors was significantly higher than that for females. Regression modelling showed a significant, positive dependence of the hip score of the offspring upon the hip scores of its sire, dam and grandparents. Genetic heritability (using data from 13,382 Labrador retrievers comprising 718 litters) was highly significant: 0.34 from the two parents, 0.41 from sire alone and 0.30 from dam alone. Using components data from 2038 offspring Labrador retrievers comprising 1248 litters, three similar estimates of heritability were significant for three major components (Norberg angle, cranial acetabular edge and subluxation); for other components, heritability was significant from the sire but not from the dam. Offspring hip score could be reduced substantially by using only parents with zero hip score.

Relationship of the degree of goniodysgenesis and other ocular measurements to glaucoma in Great Danes.

OBJECTIVES: To assess the association between goniodysgenesis, ocular measurements, and glaucoma in Great Danes. ANIMALS: 180 Great Danes. PROCEDURE: Eye examination and measurements were obtained from 180 Great Danes; for 30 of these dogs, depth of the anterior chamber, vitreal body length, and total depth of the globe were also measured. These data were merged with electronic pedigree information on 43,371 kennel club registered Great Danes. Relationships among goniodysgenesis, ocular measurements, and glaucoma and the heritability of goniodysgenesis were estimated. RESULTS: The degree of goniodysgenesis was significantly and positively associated with the likelihood of glaucoma. There was a significant association between the degree of goniodysgenesis in offspring and parents. The estimated heritability of the degree of goniodysgenesis was 0.52. The depth of the anterior chamber of the eye was also a good predictor of goniodysgenesis (ie, the dog was almost certain to have glaucoma if the depth was < 3.7 mm). If both parents had goniodysgenesis < 70%, then with 95% confidence, the occurrence of glaucoma in the ensuing offspring would be < 4/1000. This strategy translates to ensuring that the depth of the anterior chamber of the eye is > 3.7 mm for both parents. CONCLUSIONS AND CLINICAL RELEVANCE: The strong and significant correlation among goniodysgenesis, other eye measurements, and glaucoma and the significant heritability of goniodysgenesis suggests that glaucoma may be heritable in Great Danes. If so, glaucoma can be controlled by breeding only from sires and dams with a minimum degree of goniodysgenesis.

Subchondral bone thickness, hardness and remodelling are influenced by short-term exercise in a site-specific manner.

It was hypothesised that subchondral bone thickness, hardness and remodelling are influenced by exercise intensity, and by location within a joint. Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. This project aimed to determine the subchondral bone thickness, formation, resorption and hardness at sites with high and low incidence of pathology in 2 year-old horses undergoing 19 weeks high intensity treadmill training or low intensity exercise, and to compare these factors between exercise groups. Dorsal and palmar test sites were identified on radial, intermediate and third carpal articular surfaces after euthanasia. Adjacent osteochondral samples from each test site underwent histomorphometric analysis (for subchondral bone thickness, osteoid perimeter, osteoid seam width, eroded cavity area and eroded cement line surface length) and microhardness testing. Bone from horses undergoing high intensity training was thicker with a greater osteoid perimeter, and at individual sites had a smaller osteoid seam width and eroded cavity. Exercise-related differences were most marked at dorsal locations. Maximal differences in bone formation indices were observed at dorsal radial and medial third carpal locations. Overall subchondral bone from dorsal sites was thicker with a greater osteoid perimeter. Subchondral bone from dorsal sites was approximately 35% harder than bone from palmar sites. These results show topographical variations in subchondral bone structure, formation, resorption and material properties and a site-specific response to exercise. The maximal response to exercise was at high load sites with a clinical predisposition to injury. These findings indicate that the combined effect of exercise and local load variations within a joint may lead to maximal adaptive responses or overload of these responses at sites predisposed to injury.

Control of strangles outbreaks by isolation of guttural pouch carriers identified using PCR and culture of Streptococcus equi.

Previous use of repeated nasopharyngeal swabbing and culture of Streptococcus equi showed that healthy carriers developed in more than 50% of 'strangles' outbreaks. The guttural pouches were the only detectable site of S. equi colonisation on endoscopic examination of horses during one of these outbreaks and S. equi was sometimes not detected by culture of nasopharyngeal swabs from carriers for up to 2 or 3 months before nasal shedding resumed sporadically. A more sensitive way of detecting S. equi on swabs from established guttural pouch carriers was therefore required. Conveniently selected 'strangles' outbreaks were investigated in detail using endoscopy, in order to develop and assess a suitable polymerase chain reaction (PCR) test. We report here 3 protracted 'strangles' outbreaks on different kinds of establishments in which between 29 and 52% of sampled horses were infected as detected by culture and/or PCR. Of the infected horses, between 9 and 44% were identified as carrying S. equi after clinical signs had disappeared and the predominant site of carriage was the guttural pouch. Prolonged carriage of S. equi, which lasted up to 8 months, did not cease spontaneously before treatment was initiated to eliminate the infections. The detection and isolation of the carriers, in conjunction with strict hygiene measures, apparently resulted in the control of the outbreaks and allowed the premises to return to normal activity. Comparing PCR and culture, many more swabs were found to be positive using PCR (56 vs. 30% of 61 swabs). Similar results were obtained for guttural pouch samples from 12 established carriers (PCR 76% and culture 59%). These results from repeated samples from relatively few animals need confirming using more long-term carriers. PCR can also detect dead organisms and is, therefore, liable to yield false positive results. Despite this drawback, it is argued that PCR provides a potentially useful adjunct to culture of nasopharyngeal swabs in the detection of asymptomatic carriers of S. equi following outbreaks of 'strangles'.

Heritability and epidemiology of canine hip-dysplasia score in flat-coated retrievers and Newfoundlands in the United Kingdom.

Hip dysplasia (malformation of the coxofemoral joint) in dogs is a major health problem for which the British Veterinary Association (BVA) had set up a control scheme in 1965. Based on scoring nine components of the radiographs of both the left and right joints, the degree of hip joint malformation is now quantified by an overall hip score (a measure of the condition of the hip joint). The hip scores of 1258 flat-coated retrievers and 1566 Newfoundlands (registered with The Kennel Club in the United Kingdom) were analysed after merging with Kennel Club pedigree data for 19036 flat-coated retrievers registered by 1995 and 14336 Newfoundlands registered by 1997. The merged data included the animal's identity, date of birth, sex and hip scores and also similar records for the dog's relatives including the hip score if the relative had been tested. In recent years, breeding has been increasingly from tested parents. There has been some reduction in offspring hip scores - presumably because breeders avoided breeding from males with very high scores. However, a much greater reduction in offspring hip score would be achieved by stricter science-based selection of potential sires and dams. Regression modelling quantified the positive relationship between offspring and parental hip scores. The genetic heritability of hip scores was large and significant in both breeds (particularly from dams). The breeders in UK tended to use healthy sires for breeding but they have taken less care in selecting dams. Our regression models emphasise the need for both sires and dams, particularly dams, to be healthy with very small hip scores.

Heritability of canine hip-dysplasia score and its components in Gordon setters.

Hip dysplasia (malformation of the hip joint) is an important health problem in dogs. The condition and the control scheme for Gordon Setters was organised by the British Veterinary Association (BVA) and the Kennel Club before 1976 and use hip scores. Our analyses of hip dysplasia in Gordon Setters used both hip scores and the scores for the nine components (which collectively defined the hip score). The scores for all nine components were available for 732 females and 420 males. These clinical data were merged with the Kennel Club pedigree database (animal's identity, date of birth, and also similar data for its parents, including hip scores if the parent had been tested). Regression models showed strong positive relationships between offspring and parental hip scores as well as for some component scores. The heritability of hip dysplasia (assessed using both hip scores and the major components) was significant, particularly from dams. Our research emphasizes the need for both sires and dams--particularly dams, to have zero or small hip scores. Tested parents have been used increasingly in recent years, but greater reduction in offspring hip score will require stricter selection of potential breeding stock. The models reported here provide quantitative predictions of likely health benefits from selective breeding.

Risk factors for equine influenza serum antibody titres in young thoroughbred racehorses given an inactivated vaccine.

Young Thoroughbred racehorses (222 yearlings entering training and 246 2-year-old horses already in training) from eight flat-training yards in Newmarket, UK were used to monitor serological responses to vaccination with an inactivated influenza virus vaccine. Blood samples taken prior to and after vaccination were tested by single radial haemolysis (SRH) to determine antibody titres (expressed as area of haemolysis in mm(2)). Prior to vaccination, yearlings had mean antibody titres (64+/-4 mm(2)) that were approximately half of those of 2-year-olds (115+/-3 mm(2)) and 89% of yearlings and 73% of 2-year-olds had SRH titres <140 mm(2). Extrapolation from experimental and field studies suggests that these levels would not protect against homologous influenza virus infection. Both age-groups showed anamnestic responses to vaccination resulting in similar peak mean titres ( approximately 160+/-2mm(2)) with 67% of yearlings and 73% of 2-year-olds achieving levels > or =140 mm(2). A second dose of vaccine administered a month after the first in yearlings did not increase the mean titre but 75% of horses had levels of antibody > or =140 mm(2). The vaccination history in the official passport of yearlings showed that 23% had no record of previous vaccination and were probably fully susceptible to infection. For yearlings entering training, the important predictors from multiple-regression analyses of SRH titres prior to vaccination were "Time since last vaccination," "Total number of previous vaccines" and "Age at first vaccination." In 2-year-olds and following two doses of vaccine in yearlings, there was no significant relationship between these factors and SRH titre.

Inheritance of gluten-sensitive enteropathy in Irish Setters.

OBJECTIVE: To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters. ANIMALS: 44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters. PROCEDURE: Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated. RESULTS: The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE. CONCLUSIONS: Genetic transmission of GSE is under the control of a single major autosomal recessive locus.

Exercise affects the mechanical properties and histological appearance of equine articular cartilage.

Dorsal carpal osteochondral injury is a major cause of reduced performance in horses undergoing high-intensity training. It was hypothesised that the mechanical behaviour and histology of cartilage are influenced by the intensity of exercise and by location within a joint. Relationships between histology and mechanical behaviour were identified in 2-year-old horses undergoing 19 weeks of high-intensity treadmill training or low-intensity exercise and then compared between groups. Dorsal and palmar test sites were identified on radial, intermediate, and third carpal articular surfaces after euthanasia. The mechanical properties of cartilage were determined with an automated creep indentation apparatus as previously described for equine cartilage. Cartilage morphology was assessed with use of sections stained with haematoxylin and eosin and toluidine blue. Dorsal cartilage was less permeable, thinner, and had a loss of chondrocyte alignment compared with palmar cartilage. Cartilage from strenuously trained horses showed more fibrillation and chondrocyte clusters than did cartilage from gently exercised animals. Dorsal radial carpal cartilage and third carpal cartilage of strenuously trained animals were significantly less stiff than that from gently exercised animals, and the former had reduced superficial toluidine blue staining compared with that from the gently exercised group. These results indicate that topographical and exercise-related differences exist in the morphology and mechanical properties of carpal cartilage and suggest that strenuous training may lead to deterioration of cartilage at sites with a high clinical incidence of lesions.

Clindamycin hydrochloride and clavulanate-amoxycillin in the treatment of canine superficial pyoderma.

A masked, randomised, controlled clinical trial for the treatment of canine superficial pyoderma was undertaken. Dogs with a clinical diagnosis of superficial pyoderma, supported by bacterial culture were admitted to the trial and randomly assigned to treatment with either clindamycin hydrochloride at 5.5 mg/kg twice daily or clavulanate-amoxycillin at 12.5 mg/kg twice daily. After 21 days the animals were re-assessed, and therapy was continued for a further 21 days in the dogs with persistent lesions if bacterial culture demonstrated continued sensitivity. Twenty-nine dogs were treated with clindamycin hydrochloride and 27 with clavulanate-amoxycillin. Complete cure was obtained after three weeks in 17 (59 per cent) of the clindamycin-treated cases, but in only eight (30 per cent) of the clavulanate-amoxycillin treated group. Clindamycin was significantly more effective than clavulanate-amoxycillin for the treatment of superficial pyoderma in dogs.

Deafness in dalmatians: does sex matter?

Recent studies on the prevalence of deafness in Dalmatians have reported vastly different gender effects on the prevalence. The diverse conclusions in these reports cover all possibilities, higher prevalence in males, no difference between genders and higher prevalence in females. Much of this confusion about the effect of gender on the Dalmatian's hearing status is due to the unsatisfactory statistical interpretation of the available data. Careful analysis of a large (n = 1234) composite database on Dalmatians in the UK has provided a reliable assessment of the effect of gender on deafness. The overall rate of deafness in the tested Dalmatians was 18.4%, of which 13.1% were unilaterally deaf and 5.3% were bilaterally deaf. The overall deafness in females (21.1%) was significantly higher (p = 0.014) than that in males (15.5%). In all subsets of the full dataset [subsets obtained by partitioning by testing locations, colour (black or liver spots), parental hearing status normal or untested) and time (year of test)], the prevalence was higher in females compared with males. Unlike other studies, the confounding of the gender effect with other factors, particularly the parental hearing status, was avoided in the large, composite UK study. Because dogs from the same litter might be correlated with respect to their deafness status, the data were analysed further to take the random litter effect into account. This further emphasised the difference between genders. We believe that the reason for the prevailing confusion in the literature is that the unwary referees and readers give the same amount of credence to 'not significant' results from small scale studies as they give to significant results from large scale studies and do not always recognize the absence of sound statistical methods.

Pectinate ligament dysplasia (PLD) and glaucoma in Flat Coated Retrievers. I. Objectives, technique and results of a PLD survey.

Pectinate ligament dysplasia (PLD) in dogs is a congenital ocular abnormality affecting the iridocorneal angle, the presence of which may be associated with adult-onset primary glaucoma. This paper describes the objectives, methods and results of a survey of PLD in Flat Coated Retrievers in the UK, including the technique used for gonioscopic assessment of the degree of PLD. In a random sample of 389 Flat Coated Retrievers, 34.7% were found to have a degree of PLD. In a 'target' sample of 48 Flat Coated Retrievers (close relatives of dogs from the random sample with high degrees of PLD, or dogs presented with primary glaucoma), 83.3% were found to have a degree of PLD. The percentage of animals with a degree of PLD was only 6.0% in a 'control' sample of 100 dogs from other breeds. The relationship between PLD and canine glaucoma is discussed.

Pectinate ligament dysplasia and glaucoma in Flat Coated Retrievers. II. Assessment of prevalence and heritability.

Pectinate ligament dysplasia (PLD) in dogs is a congenital ocular abnormality affecting the iridocorneal angle, the presence of which may be associated with adult-onset primary glaucoma. This study demonstrates a significant association between PLD and glaucoma in Flat Coated Retrievers, and also a higher prevalence of PLD in Flat Coated Retrievers compared with other breeds. It is shown that the association between PLD and glaucoma was robust and not due to a small increase in PLD with age. There was also a significant association between PLD in offspring and parents and, using the offspring-parents regression, the heritability of PLD was estimated as approximately 0.7. As glaucoma is significantly related to PLD, glaucoma may also be heritable. Thus, glaucoma can be controlled by gonioscopic examination and elimination of animals with a high degree of PLD from a breeding program. Breeding from only those animals with a moderate or low PLD value or score should limit the expected prevalence of glaucoma in the resulting population to < 0.2%. The preceding study describes in detail the PLD survey, gonioscopic technique and some initial results obtained prior to this epidemiological investigation.

Prevalence and prevention of deafness in the Dalmatian--assessing the effect of parental hearing status and gender using ordinary logistic and generalized random litter effect models.

The Dalmatian dog is susceptible to congenital deafness which is thought to be inherited. The condition cannot be treated or cured, but controlled breeding could prevent or minimize the occurrence. An understanding of the quantitative relationship between the relevant attributes (sex, colour etc.) and the probability of deafness is likely to be of assistance in implementing any breeding programme to eliminate the condition. Most reported studies on Dalmatians have ignored the hearing status of close parental relatives, and none has taken into account the likely positive correlations in dogs from same litters. A composite database, obtained by merging deafness data on 1234 tested Dalmatians with Kennel Club pedigree data on 22,873 Dalmatians in the United Kingdom, has enabled us to include the hearing status of parental relatives and litter effects in our analysis. Contingency tables and ordinary logistic regression were used to obtain preliminary results which could be compared with the findings from other studies based on similar analyses. Further logistic modelling included an additional random effects term for the effect of litters to which the dogs belonged. The preliminary analysis showed that the prevalence of overall deafness in the tested Dalmatians was 18.4%, of which 13.1% were unilaterally deaf, and 5.3% were bilaterally deaf. There was no association between deafness and either testing location or coat colour but prevalence was strongly associated with parental hearing status. In Dalmatians from normal dams the prevalence (15.6%) was significantly lower than in those from untested dams (21.9%). If the parents were both normal or both untested, these figures were 15.3 and 23.6%, respectively, and significantly different. There was a significant gender effect, the prevalence being significantly higher in females (21.1%) than in males (15.5%), and this was seen in all subsets of data partitioned by parental hearing status, by locations, and by dominant coat colours. The use of generalized modelling, which included the random litter effects yielded point estimates of the prevalence of deafness which were smaller, but with wider confidence limits. Breeding from only tested and proven normal dams and sires is therefore recommended, and should reduce overall deafness to below 15% and bilateral deafness to below 4%.