Breeding implications resulting from classification of patellae luxation in dogs.

Patellar luxation (PL) is one of the major hereditary orthopaedic abnormalities observed in a variety of dog breeds. When the patellae move sideways out of the trochlear groove, this is called PL. The PL score varies between dogs from normal to very severe. Reducing the prevalence of PL by breeding could prevent surgery, thereby improve welfare. Orthopaedic specialists differentiate between normal and loose patellae, where the patellae can be moved to the edge of the trochlear groove, considering scoring loose patellae as normal in the future. Loose patellae are considered acceptable for breeding so far by the breeding organization. The aim of this study was to analyse the genetic background of PL to decide on the importance of loose patellae when breeding for healthy dogs. Data are available from two dog breeds, that is Flat-coated Retrievers (n = 3808) and Kooiker dogs (n = 794), with a total of 4602 dogs. Results show that loose patellae indicate that dogs are genetically more susceptible to develop PL because family members of the dogs with loose patellae showed more severe PL. In addition, the estimated breeding values for dogs with loose patellae indicate that breeding values of dogs with loose patellae were worse than breeding values obtained for dogs with a normal score. Given these results, it is advised to orthopaedic specialists to continue to score loose patellae as a separate class and to dog breeders to minimize the use of dogs in breeding with a genetically higher susceptibility for PL.

Phenotypic and genetic relationships of bovine natural antibodies binding keyhole limpet hemocyanin in plasma and milk.

To improve the health status (resilience) of dairy cows, levels of natural antibodies (NAb) might be useful. The objective of the present study was to compare levels and to estimate genetic parameters for NAb measured in milk and plasma samples. Titers of NAb IgM and IgG isotype-binding keyhole limpet hemocyanin of 2,919 cows, in both plasma and milk, were measured using ELISA. Analysis revealed that NAb levels in milk significantly increased with parity, whereas they remained constant in plasma. Moderate positive phenotypic correlations were found between NAb levels in milk and in plasma: 0.18 for IgG and 0.40 for IgM. This indicates that NAb from milk and plasma might reflect different aspects of dairy cow health status. However, high genetic correlations were found for NAb in milk and plasma: 0.81 for IgG and 0.79 for IgM. Heritabilities (SE in parentheses) for NAb measured in plasma [0.15 (0.05) for IgG and 0.25 (0.06) for IgM] were higher than heritabilities of NAb measured in milk [0.08 (0.03) for IgG and 0.23 (0.05) for IgM]. Our results indicate that NAb measured in milk and plasma are heritable and likely have a common genetic background, suggesting that NAb levels measured in milk might be useful for genetic improvement of disease resistance.

The effect of genetic selection for Johne's disease resistance in dairy cattle: Results of a genetic-epidemiological model.

The objective of this study was to model genetic selection for Johne's disease resistance and to study the effect of different selection strategies on the prevalence in the dairy cattle population. In the Netherlands, a certification-and-surveillance program is in use to reduce prevalence and presence of sources of infection in milk by culling ELISA-positive dairy cows in infected herds. To investigate the additional genetic effect of this program, a genetic-epidemiological model was developed to assess the effect of selection of cows that test negative for Johne's disease (dam selection). The genetic effect of selection at the sire level was also considered (sire selection), assuming selection of 80% of sires producing the most resistant offspring based on their breeding values, as well as the combined effect. Parameters assumed to be affected by genetic selection were the length of the latent period, susceptibility (i.e., the number of infectious doses needed to become infected), or the length of susceptible period as a calf. The effect of selection was measured by the time in years required to eliminate infection. Sensitivity analysis was performed for heritability, accuracy of selection, and intensity of selection. For dam selection, responses to selection were small, requiring 379 to 702 yr for elimination. For sire selection, responses were much larger, although elimination still required 147 to 223 yr. The response to selection was largest if genetic selection affected the length of the susceptible period, followed by the susceptibility, and finally the length of the latent period. Genetic selection for Johne's disease resistance by certification and surveillance is too slow for practical purpose, but that selection on the sire level is able to contribute to the control of Johne's disease in the long run.

Phenotypic and genetic trends of patellar luxation in Dutch Flat-Coated Retrievers.

Canine patellar luxation has been described in various dog breeds, with high prevalence especially in smaller dogs. Most dogs suffer from medial displacement of the patella, although in larger dogs lateral displacement is also seen. A sex predisposition has been described for females. Patellar luxation is considered a polygenic, multifactorial disorder. From 1990 to 2007, in total 3834 Flat-Coated Retrievers were screened; 23.6% of those animals were affected with patellar luxation. Lateral displacement of the patella was most common in this breed (61% of cases), whereas medial (31% of cases) and lateral and medial (8% of cases) were less common. Unilateral involvement (51% of cases) was just as often observed as was bilateral involvement (49% of cases). Females were more often affected with patellar luxation (30% of all tested females) than were males (17% of all tested males). The heritability of patellar luxation was 0.17 ± 0.03 in this population, and breeding with one affected parent increased the prevalence of patellar luxation in offspring by 45% compared to that with two unaffected parents. Since the start of the screening program, there was an initial decrease from 28% to 18% in incidence, but this stagnated thereafter. The annual average estimated breeding values followed the same pattern. With approximately one quarter of the Dutch Flat-Coated Retrievers being affected with patellar luxation, this population shows unusually high prevalence compared with reports in other large-breed dogs. The heritability for patellar luxation in this population was moderate (0.17), indicating that environmental factors play a large role in the manifestation of the disorder. A screening program reduced the prevalence of patellar luxation in this breed, but improvement has recently stagnated. Inclusion of breeding values in the screening program could improve its effectiveness.

Genetic and nongenetic variation in plasma and milk ß-hydroxybutyrate and milk acetone concentrations of early-lactation dairy cows.

This study assessed genetic variation, heritability estimates, and genetic correlations for concentrations of plasma ß-hydroxybutyrate (BHBA), milk BHBA, and milk acetone in early lactation to investigate differences between cows in susceptibility to hyperketonemia and possibilities to use test-day milk ketone bodies for genetic improvement. Blood and test-day milk samples were collected on randomly selected dairy farms in the Netherlands from cows of various parities between 5 and 60 d in milk. Plasma samples were analyzed for BHBA (reference test for hyperketonemia) and test-day milk samples were analyzed for BHBA and acetone using Fourier-transform infrared spectroscopy. The final data set consisted of plasma BHBA concentrations of 1,615 cows from 122 herds. Milk BHBA and milk acetone concentrations were determined for 1,565 cows. Genetic variation, heritability, and proportion of phenotypic variation attributable to the herd were estimated using an animal model with fixed effects for parity and season, a covariate for days in milk, and random effects for herd, animal, and error. Genetic correlations for plasma BHBA, milk BHBA, and milk acetone were estimated using bivariate analyses. The heritability estimate for plasma BHBA concentrations in early lactation was 0.17, whereas heritability estimates for milk BHBA and milk acetone were 0.16 and 0.10, respectively. This indicates that selective breeding may contribute to a lower incidence of hyperketonemia in early lactation. For the 3 traits, the proportion of variance attributable to herd was larger than the additive genetic variance, underlining the importance of on-farm feeding and management in the etiology of hyperketonemia in fresh cows. Prevention strategies for hyperketonemia can, therefore, include both feeding and management strategies at dairy farms (short-term) and genetic improvement through breeding programs (long-term). Genetic correlations between concentrations of plasma BHBA and milk BHBA (0.52) or milk acetone (0.52) were moderate. As milk ketone bodies can be routinely analyzed at test days, this may provide a practical alternative for breeding programs aimed at reducing hyperketonemia in early lactation.

Genetic variation for infection status as determined by a specific antibody response against Mycobacterium avium subspecies paratuberculosis in milk of Dutch dairy goats.

Classical control strategies based on management restrictions to reduce transmission, culling of infected goats, and vaccination have not been able to eradicate Johne's disease from infected herds. Selective breeding for less susceptibility to disease may be a useful additional tool to contribute to control of the disease. The aim of this study was to estimate genetic variation and heritability for infection status as determined by a specific antibody response against Mycobacterium avium subspecies paratuberculosis in milk of Dutch dairy goats. Milk samples from 950 goats were tested for antibodies specific to Johne's disease by ELISA on 5 consecutive test days, with a time interval of around 3 mo. Test results were coded as infected or not infected according to the instructions of the manufacturer. Heritability of infection status was estimated for 3 data sets to determine the effect of repeated sampling: only test results obtained on the first test day (first-test); the maximum test result of each animal obtained on 1 of the 5 test days (max-test); and all test results per animal, with a maximum of 5 consecutive samplings (all-test). Data sets first-test and max-test were analyzed with a sire model with fixed effects for year of birth and stage of lactation, and random effects for sire and error. For data set all-test, an additional permanent environment effect was included in the model. The estimated heritability on the underlying scale ranged from 0.12 in data set first-test, to 0.09 in data set max-test, to 0.07 in data set all-test.

Genome-wide association study to identify chromosomal regions associated with antibody response to Mycobacterium avium subspecies paratuberculosis in milk of Dutch Holstein-Friesians.

Heritability of susceptibility to Johne's disease in cattle has been shown to vary from 0.041 to 0.159. Although the presence of genetic variation involved in susceptibility to Johne's disease has been demonstrated, the understanding of genes contributing to the genetic variance is far from complete. The objective of this study was to contribute to further understanding of genetic variation involved in susceptibility to Johne's disease by identifying associated chromosomal regions using a genome-wide association approach. Log-transformed ELISA test results of 265,290 individual Holstein-Friesian cows from 3,927 herds from the Netherlands were analyzed to obtain sire estimated breeding values for Mycobacterium avium subspecies paratuberculosis (MAP)-specific antibody response in milk using a sire-maternal grandsire model with fixed effects for parity, year of birth, lactation stage, and herd; a covariate for milk yield on test day; and random effects for sire, maternal grandsire, and error. For 192 sires with estimated breeding values with a minimum reliability of 70%, single nucleotide polymorphism (SNP) typing was conducted by a multiple SNP analysis with a random polygenic effect fitting 37,869 SNP simultaneously. Five SNP associated with MAP-specific antibody response in milk were identified distributed over 4 chromosomal regions (chromosome 4, 15, 18, and 28). Thirteen putative SNP associated with MAP-specific antibody response in milk were identified distributed over 10 chromosomes (chromosome 4, 14, 16, 18, 19, 20, 21, 26, 27, and 29). This knowledge contributes to the current understanding of genetic variation involved in Johne's disease susceptibility and facilitates control of Johne's disease and improvement of health status by breeding.

Effect of herd prevalence on heritability estimates of antibody response to Mycobacterium avium subspecies paratuberculosis.

Worldwide, classical control strategies based on hygiene and culling of infected animals have been implemented to eradicate Johne's disease. Breeding for disease resistance may be a useful additional tool to control the disease. The aim of this study was to estimate genetic parameters for the presence of a Mycobacterium avium ssp. paratuberculosis specific antibody response in milk of Dutch Holstein-Friesian cows using subsets of data based on within-herd test prevalence. The analyzed data set consisted of milk samples of 684,364 animals from 12,077 herds collected during the routine milk production scheme. Milk samples were tested for antibodies specific for Johne's disease by an ELISA test. Heritability estimates were calculated for 4 different subsets of data to determine the sensitivity of heritability for within-herd test prevalence. Results expressed as percentage of the sample to positive ratio were analyzed with a sire-maternal grandsire model with fixed effects for parity, year of birth, lactation stage, and herd; a covariate for milk yield at test day; and random effects for sire, maternal grandsire, and error. The estimated heritability ranged from 0.031 for the complete data set to 0.097 for herds with a test prevalence of at least 10%. Cross-validation was applied to determine which of the subsets of data produced the most accurate estimated breeding values. Results showed that for genetic selection to contribute to disease control, breeding values were estimated most accurately from herds with at least 2 animals that tested positive. In this subset the heritability was 0.041.

Mapping markers linked to porcine salmonellosis susceptibility.

The goal of this study was to identify pig chromosomal regions associated with susceptibility to salmonellosis. Genomic DNA from pig reference populations with differences in susceptibility to Salmonella enterica serovar Choleraesuis as quantified by spleen and liver bacterial colonization at day 7 post-infection (dpi; Van Diemen et al. 2002) was used. These samples belonged to the offspring of a sire thought to be heterozygous for genes involved in susceptibility to salmonellosis. Amplified fragment length polymorphism (AFLP) markers were created and used to determine associations with spleen or bacterial counts at 7 dpi. To position linked markers, two mapping populations, the Roslin and Uppsala PiGMaP pedigrees were used to create an integrated map which included the AFLP markers associated with salmonellosis. Twenty-six AFLP markers located in 14 different chromosomal regions in the porcine genome were found to be significantly associated with susceptibility (Chi-square P < 0.05). More than one linked marker was found on chromosomes 1, 7, 13, 14 and 18. It is likely that these regions contain genes involved in Salmonella susceptibility. Regions on chromosomes 1, 7 and 14 were significantly associated with Salmonella counts in the liver and regions on chromosomes 11, 13 and 18 with counts in spleen. The identification of these chromosomal regions highlights specific areas to search for candidate genes that may be involved in innate or adaptive immunity. Further investigation into these chromosomal regions would be useful to improve our understanding of host responses to infection with this widespread pathogen.

Evidence of inheritance of intrahepatic portosystemic shunts in Irish Wolfhounds.

BACKGROUND: The etiogenesis of congenital portosystemic shunt in dogs is not understood. In Irish Wolfhounds, intrahepatic portosystemic shunt (IHPSS) is thought to be hereditary, but the mode of inheritance is unknown. OBJECTIVES: To document the genetic background and investigate the potential mode of inheritance of IHPSS in Irish Wolfhounds. ANIMALS: Three mature, privately owned, affected siblings and their progeny produced in 2 litters. METHODS: Prospective, observational study. Two test matings of 1 affected sire with 2 of his affected sisters were used to determine the inheritance pattern. Affection status was determined by measuring venous blood ammonia concentrations, detection of the shunt by ultrasonography and confirmation during surgical attenuation of the intrahepatic shunting vessel. RESULTS: In 1 litter of 5 pups all had an IHPSS. In the other litter 5 of 11 pups were affected. Both left- and right-sided shunts occurred in both litters. No sex predisposition was evident among affected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results show that IHPSS in Irish Wolfhounds is a familial disorder that is likely genetic. It is unlikely that the mode of inheritance is monogenic. A digenic, triallelic trait could explain the observed occurrence of IHPSS but other modes of inheritance cannot be excluded.

Identification of environmental factors affecting the prevalence of insect bite hypersensitivity in Shetland ponies and Friesian horses in The Netherlands.

REASONS FOR PERFORMING STUDY: It is expected that climate and habitat factors influence the prevalence of culicoides and, therefore, the prevalence of insect bite hypersensitivity (IBH), but very little is described in the literature to prove the association of these factors. Prevalence varies widely from 3% in certain areas of Great Britain to 60% in certain parts of Australia. OBJECTIVES: To describe the influence of environmental factors on the prevalence of IBH in Shetland ponies and Friesian horses in The Netherlands. METHODS: Data on 3284 Shetland and 2824 Friesian mares (n = 6108) were collected in The Netherlands, based on 90 regions, according to postal codes. The climate components, amount of rainfall, number of warm days, number of cold days, and habitat components of soil type and type of vegetation were collected for each region. RESULTS: Prevalence of IBH varied widely from 0-71.4% per region. The results showed that the environment with low IBH-prevalence had high rainfall, many cold days and few warm days per year. Habitats with a low IBH-prevalence were based along the coast line. Habitats with increasing prevalence of IBH had soils of clay with heather and woody vegetation. Friesian mares had a higher IBH prevalence than Shetland mares, which could indicate an effect of genetic background or an effect of year. CONCLUSIONS: There is an environmental effect on IBH prevalence within The Netherlands, which is caused by climate and habitat factors. POTENTIAL RELEVANCE: The results provide a more accurate description of environmental factors and their impact on development of IBH; and should help better to understand habitat and climate effects, and to distinguish these from other effects, such as animal factors (genetics, age or sex).

Population genetic analysis and genome-wide association study of patellar luxation in a Thai population of Pomeranian dogs.

The genetics of patellar luxation (PL) were investigated in Pomeranian dogs presented at the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. A cohort of 339 Pomeranian dogs, part of a four-generation pedigree of 842 Pomeranians, was screened for PL from 2006 to 2013. PL was present in 77% of the screened dogs, with 84% having bilateral and 16% unilateral luxation. Medial PL was more common (95%) than lateral PL (2%) or bidirectional PL (3%). The risk of PL was similar in male and female dogs (female:male relative risk 1.11, 95% CI 0.98-1.25). The heritability of PL in the screened population was 0.44±0.04 using a threshold model. A genome-wide association study of PL (48 cases and 48 controls) using a high-density SNP array indicated the possible involvement of 15 chromosomal regions, of which CFA05 and CFA32 remained associated in a larger study involving an additional 128 cases and 7 controls. Candidate genes in these regions may be involved in the pathogenesis of PL in Pomeranian dogs.

Prevalence and genetics of patellar luxation in Kooiker dogs.

The prevalence of patellar luxation (PL) and genetic factors potentially involved in the disorder were investigated in Dutch Kooiker dogs. A cohort of 842 Kooiker dogs, the offspring of 195 sires and 318 dams, was screened for PL from 1994 to 2011. The cohort was included in a pedigree of 1737 Kooiker dogs comprising nine generations. PL was present in 24% of screened dogs, with unilateral and bilateral luxation being observed equally frequently. Medial PL was more common (61%) than lateral PL (32%) or bidirectional PL (7%). The frequency of PL was similar in male and female dogs, with a female:male relative risk of 1.15 (95% confidence interval, CI, 0.90-1.48). The heritability of PL in the screened population was 0.27 ± 0.07. Since the start of the screening programme, the prevalence of PL decreased from 28% to 19%. A genome-wide association study of PL with 48 cases and 42 controls suggested the possible involvement of a region on chromosome 3 (Praw = 1.32 × 10(-)(5), Pgenome = 0.142), but the involvement of this region could not be confirmed in a validation group. Breeding programmes for complex diseases, such as PL, would benefit from combining pedigrees, phenotypes and genotypes, i.e. from genomic selection, as is currently the method of choice for breeding of production animals.

Skeletal and hepatic changes induced by chronic vitamin A supplementation in cats.

The first aim of this study was to determine whether vitamin D supplementation influenced the effects of high vitamin A intake on new bone formation in adult cats. The second aim was to determine whether high vitamin A intake in cats caused liver pathology and, if so, whether the current upper limit for the dietary intake of vitamin A for healthy adult cats would be safe. Twenty-four healthy adult cats were divided into four groups that received a control diet supplemented with peanut oil (control), or peanut oil containing a 100-fold increase in vitamin A (HA), or a 100-fold increase in vitamin A and a fivefold increase in vitamin D (HAMD), or a 100-fold increase in vitamin A and a 65-fold increase in vitamin D (HAHD) over a period of 18 months. Cats did not show abnormal locomotion or clinical signs of liver failure after 18 months of supplementation but did show subtle skeletal changes and liver pathology, suggesting that the current National Research Council (2006) safe upper limit for vitamin A for cats is too high. The addition of vitamin D did not seem to influence bone pathology. While moderately elevated dietary vitamin D levels (HAMD) seemed to protect cats against the liver pathology caused by the consumption of large amounts of vitamin A, higher dietary levels of vitamin D (HAHD) did not seem to be protective.

Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure-bred dogs.

Hip as well as elbow dysplasia (HD, ED) are developmental disorders leading to malformation of their respective joints. For a long time both disorders have been scored and targeted for improvement using selective breeding in several Dutch dog populations. In this paper all scores for both HD and ED, given to pure bred dogs in the Netherlands from 2002 to 2010, were analyzed. Heritabilities and correlations between HD and ED were calculated for the 4 most frequently scored breeds. Heritabilities ranged from 0.0 to 0.37 for HD related traits (FCI-score, osteoarthritis, congruity, shape and laxity (Norberg angle); FCI: Fédération Cynologique Internationale) and from 0.0 to 0.39 for ED related traits (IEWG score, osteoarthritis, sclerosis and indentation; IEWG: International Elbow Working Group). HD related traits showed high genetic and residual correlations among each other but were only to a minor extent correlated with ED related traits, which also showed high correlations among each other. Genetic correlations were higher than residual correlations. Phenotypic and genetic trends since 2001 for the four most scored breeds were slightly positive but decreasing over time, indicating that selection over the past decade has not been effective.

Heritable and non-heritable genetic effects on retained placenta in Meuse-Rhine-Yssel cattle.

Failure of the timely expulsion of the fetal membranes, called retained placenta, leads to reduced fertility, increased veterinary costs and reduced milk yields. The objectives of this study were to concurrently look at the heritable and non-heritable genetic effects on retained placenta and test the hypothesis that a greater coefficient of relationship between dam and calf increases the risk of retained placenta in the dam. The average incidence of retained placenta in 43,661 calvings of Meuse-Rhine-Yssel cattle was 4.5%, ranging from 0% to 29.6% among half-sib groups. The average pedigree based relationship between the sire and the maternal grandsire was 0.05 and ranged from 0 to 1.04. Using a sire-maternal grandsire model the heritability was estimated at 0.22 (SEM=0.07) which is comparable with estimates for other dual purpose breeds. The coefficient of relationship between the sire and the maternal grandsire had an effect on retained placenta. The coefficient of relationship between the sire and the maternal grandsire was used as a proxy for the coefficient of relationship between dam and calf, which is correlated with the probability of major histocompatibility complex (MHC) class I compatibility between dam and calf. MHC class I compatibility is an important risk factor for retained placenta. Although the MHC class I haplotype is genetically determined, MHC class I compatibility is not heritable. This study shows that selection against retained placenta is possible and indicates that preventing the mating of related parents may play a role in the prevention of retained placenta.

Phenotypic and genetic evaluation of elbow dysplasia in Dutch Labrador Retrievers, Golden Retrievers, and Bernese Mountain dogs.

Canine elbow dysplasia encompasses four developmental diseases: ununited anconeal process, osteochondrosis of the medial part of the humeral condyle, fragmented medial coronoid process (FCP), and incongruity of the elbow joint. Four radiographic views per joint were used to evaluate 2693 Labrador Retrievers (LRs), 1213 Golden Retrievers (GRs), and 974 Bernese Mountain Dogs (BMDs) for the presence of elbow dysplasia between 2002 and 2009 in the Netherlands. The views were also graded for signs of osteoarthritis and sclerosis. FCP was diagnosed most frequently in LRs, GRs and BMDs, with an incidence of 6%, 5%, and 15%, and a heritability of 0.17, 0.24, and 0.06, respectively. Heritabilities were estimated using a sire model and all available ancestors. Sclerosis at the base of the medial coronoid process was the radiographic sign most strongly correlated with FCP (r=0.95, 0.92, and 0.95 in LRs, GRs and BMDs, respectively). The sex of the dog was significantly correlated with the presence of osteoarthritis in LRs, but not in GRs and BMDs. Male LRs were 1.7-fold more frequently, but not more severely, affected by osteoarthritis than female dogs. Age at radiographic examination was significantly associated with osteoarthritis in all three breeds. The heritability estimates in Retrievers were high enough to warrant including FCP findings in the breeding policy, but until the biomechanical and genetic background of elbow dysplasia are better understood, correct phenotyping with a sensitive technique is essential.