SNP-based heritability and genetic architecture of cranial cruciate ligament rupture in Labrador Retrievers

Cranial cruciate ligament rupture (CCLR) is one of the leading causes of pelvic limb lameness in dogs. About 6% of Labrador Retrievers suffer from this orthopedic problem. The aim of this study was to determine the heritability of CCLR in this breed using SNP array genotyping data. DNA samples were collected from CCLR-affected dogs (n = 190) and unaffected dogs over the age of 8 years (n = 143). All 333 dogs were genotyped directly or imputed up to approximately 710k SNPs on the Affymetrix Axiom CanineHD SNP array. Heritability of CCLR was calculated using multiple methodologies, including linear mixed models, Bayesian models and a model that incorporates LD. The covariates of sex and sterilization status were added to each analysis to assess their impact. Across the algorithms of these models, heritability ranged from 0.550 to 0.886, depending on covariate inclusion. The relatively high heritability for this disease indicates that a substantial genetic component contributes to CCLR in the Labrador Retriever.     

Contact forces in several TKA designs during squatting: A numerical sensitivity analysis

Total knee arthroplasty (TKA) is a very successful procedure, but pain or difficulties during activities still persist in patients. Patient outcomes in TKA surgery can be affected by implant design, alignment or patient-related anatomical factors. This paper presents a numerical sensitivity analysis of several TKA types: a fixed bearing, posterior stabilized prosthesis, a high flexion fixed bearing guided motion prosthesis, a mobile bearing prosthesis and a hinge prosthesis. Each prosthesis was virtually implanted on the same cadaver leg model and it underwent a loaded squat, in 10s, between 0° and 120°, similar to several previous experimental tests performed on knee kinematics simulators. The aim of this examination was to investigate the sensitivity of the patello-femoral (PF) and tibio-femoral (TF) contact forces to patient-related anatomical factors, and component position in the different implant types. The following parameters were used for the sensitivity study: the proximo-distal patellar position, the patellar component tilting, the tibial component position and orientation, the locations of the medial and lateral collateral ligaments with respect to femur and tibia and the patellar tendon length. The sensitivity analysis showed that PF contact forces are mostly affected by patella height (increases up to 67% for one TKA type in patella-alta configuration), by an anterior tibial component translation (increases up to 30%), and by patellar component tilting (increases up to 29%); TF contact forces are mostly affected by the anterior displacement of the insertion points of the medial collateral ligament with respect to the reference position (increases up to 48%).     

Muscular dystrophy in the Japanese Spitz: an inversion disrupts the DMD and RPGR genes

An X‐linked muscular dystrophy, with deficiency of full‐length dystrophin and expression of a low molecular weight dystrophin‐related protein, has been described in Japanese Spitz dogs. The aim of this study was to identify the causative mutation and develop a specific test to identify affected cases and carrier animals. Gene expression studies in skeletal muscle of an affected animal indicated aberrant expression of the Duchenne muscular dystrophy (dystrophin) gene and an anomaly in intron 19 of the gene. Genome‐walking experiments revealed an inversion that interrupts two genes on the X chromosome, the Duchenne muscular dystrophy gene and the retinitis pigmentosa GTPase regulator gene. All clinically affected dogs and obligate carriers that were tested had the mutant chromosome, and it is concluded that the inversion is the causative mutation for X‐linked muscular dystrophy in the Japanese Spitz breed. A PCR assay that amplifies mutant and wild‐type alleles was developed and proved capable of identifying affected and carrier individuals. Unexpectedly, a 7‐year‐old male animal, which had not previously come to clinical attention, was shown to possess the mutant allele and to have a relatively mild form of the disease. This observation indicates phenotypic heterogeneity in Japanese Spitz muscular dystrophy, a feature described previously in humans and Golden Retrievers. With the availability of a simple, fast and accurate test for Japanese Spitz muscular dystrophy, detection of carrier animals and selected breeding should help eliminate the mutation from the breed.     

A three-dimensional anatomical model of the human patello-femoral joint,for the determination of patello-femoral motions and contact characteristics

The object of this study is to develop a three-dimensional mathematical model of the patello-femoral joint, which is modelled as two rigid bodies representing a moving patella and a fixed femur. Two-point contact was assumed between the femur and patella at the medial and lateral sides and in the analysis, the femoral and patellar articular surfaces were mathematically represented using Coons' bicubic surface patches. Model equations include six equilibrium equations and eleven constraints: six contact conditions, four geometric compatibility conditions, and the condition of a rigid patellar ligament; the model required the solution of a system of 17 nonlinear equations in 17 unknowns, its response describing the six-degress-of-freedom patellar motions and the forces acting on the patella. Patellar motions are described by six motion parameters representing the translations and rotations of the patella with respect to the femur. The forces acting on the patella include the medial and lateral component of patello-femoral contact and the patellar ligament force, all of which were represented as ratios to the quadriceps tendon force. The model response also includes the locations of the medial and lateral contact points on the femur and the patella. A graphical display of its response was produced in order to visualize better the motion of the components of the extensor mechanism.Model calculations show good agreement with experimental results available from the literature. The patella was found to move distally and posteriorly on the femoral condyles as the knee was flexed from full extension. Results indicate that the relative orientation of the patellar ligament with respect to the patella remains unchanged during this motion. The model also predicts a patellar flexion which always lagged knee flexion.Our calculations show that as the angle of knee flexion increased, the lateral contact point moved distally on the femur without moving significantly either medially or laterally. The medial contact point also moved distally on the femur but moved medially from full extension to about 40° of knee flexion, then laterally as the knee flexion angle increased. The lateral contact point on the patella did not change significantly in the medial and lateral direction as the knee was flexed; however, this point moved proximally toward the basis of the patella with knee flexion. The medial contact point also moved proximally on the patella with knee flexion, and in a similar manner the medial contact point on the patella moved distally with flexion from full extension to about 40° of flexion. However, as the angle of flexion increased, the medial contact point did not move significantly in the medial-lateral direction.Model calculations also show that during the simulated knee extension exercise, the ratio of the force in the patellar ligament to the force in the quadriceps tendon remains almost unchanged for the first 30° of knee flexion, then decreases as the angle of knee flexion increases. Furthermore, model results show that the lateral component of the patello-femoral contact force is always greater than the medial component, both components increasing with knee flexion.     

Genetic evaluation of hip score in UK Labrador Retrievers

Hip dysplasia is an important and complex genetic disease in dogs with both genetic and environmental influences. Since the osteoarthritis that develops is irreversible the only way to improve welfare, through reducing the prevalence, is through genetic selection. This study aimed to evaluate the progress of selection against hip dysplasia, to quantify potential improvements in the response to selection via use of genetic information and increases in selection intensity, and to prepare for public provision of estimated breeding values (EBV) for hip dysplasia in the UK. Data consisted of 25,243 single records of hip scores of Labrador Retrievers between one and four years old, from radiographs evaluated between 2000 and 2007 as part of the British Veterinary Association (BVA) hip score scheme. A natural logarithm transformation was applied to improve normality and linear mixed models were evaluated using ASREML. Genetic correlations between left and right scores, and total hip scores at one, two and three years of age were found to be close to one, endorsing analysis of total hip score in dogs aged one to three as an appropriate approach. A heritability of 0.35±0.016 and small but significant litter effect (0.07±0.009) were estimated. The observed trends in both mean hip score and mean EBV over year of birth indicate that a small genetic improvement has been taking place, approximately equivalent to avoiding those dogs with the worst 15% of scores. Deterministic analysis supported by simulations showed that a 19% greater response could be achieved using EBV compared to phenotype through increases in accuracy alone. This study establishes that consistent but slow genetic improvement in the hip score of UK Labrador Retrievers has been achieved over the previous decade, and demonstrates that progress may be easily enhanced through the use of EBVs and more intense selection.     

Toward the most ideal case–control design with related and unrelated dogs in whole‐exome sequencing studies

With the recent development of whole‐exome sequencing enrichment designs for the dog, a novel tool for disease‐association studies became available. The aim of disease‐association studies is to identify one or a very limited number of putative causal variants or genes from the large pool of genetic variation. To maximize the efficiency of these studies and to provide some directions of what to expect, we evaluated the effect on variant reduction for various combinations of cases and controls for both dominant and recessive types of inheritance assuming variable degrees of penetrance and detectance. In this study, variant data of 14 dogs (13 Labrador Retrievers and one Dogue de Bordeaux), obtained by whole‐exome sequencing, were analyzed. In the filtering process, we found that unrelated dogs from the same breed share up to 70% of their variants, which is likely a consequence of the breeding history of the dog. For the designs tested with unrelated dogs, combining two cases and two controls gave the best result. These results were improved further by adding closely related dogs. Reduced penetrance and/or detectance has a drastic effect on the efficiency and is likely to have a profound effect on the sample size needed to elucidate the causal variant. Overall, we demonstrated that sequencing a small number of dogs results in a marked reduction of variants that are likely sufficient to pinpoint causal variants or genes.     

Factors affecting gestation duration in the bitch

A retrospective analysis was performed to determine the effects of age, breed, parity, and litter size on the duration of gestation in the bitch. Bitches at two locations were monitored from breeding to whelping. A total of 764 litters whelped from 308 bitches (36 large hounds, 34 Golden Retrievers, 23 German Shepherd Dogs (GSD), and 215 Labrador Retrievers). By breed, the number of whelpings was 152, 72, 58, and 482 for the hounds, Golden Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. Whelping was predicted to be 57 d from the first day of cytologic diestrus in the hounds or 65 d from the initial progesterone rise in the other breeds. The average gestation duration (calculated as 8 d prior to Day 1 of cytologic diestrus in hounds or measured from the initial progesterone rise in other breeds) by breed (days +/- S.D.) was 66.0 +/- 2.8, 64.7 +/- 1.5, 63.6 +/- 2.1, and 62.9 +/- 1.3 for the hounds, Golden Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. The relationship of age, breed, parity, and litter size with the difference in gestation duration was evaluated using log linear modeling. Age or parity had no effect on gestation duration. Compared to Labrador Retrievers, the German Shepherd Dogs, Golden Retrievers and hounds were more likely to have a longer gestation duration; three, four and nearly eight times as likely, respectively. Bitches whelping four or fewer pups were significantly more likely to have a longer gestation duration than those whelping five or more pups; the prolongation averaging 1 d.     

Patellar taping increases vastus medialis oblique activity in the presence of patellofemoral pain.

A common rehabilitation strategy for patellofemoral pain syndrome (PFPS), which lacks scientific evidence, includes pulling the patella medially with tape to reduce pain and increase the vastus medialis oblique (VMO) muscle activity. The purpose of this study was to examine the effect of various patellar taping procedures on force production, EMG activity of the VMO and vastus lateralis (VL) muscles, and perceived pain experienced by 30 women (27.3 +/- 1.53), half diagnosed with PFPS. The perceived pain, force, and EMG of the VMO and VL, were recorded while subjects performed maximal isokinetic leg presses at 30 degrees /s for each of the following patellar taping conditions: no tape (control), no glide (placebo), medial and lateral glide (experimental). The medial and placebo procedures significantly (P < 0.01) reduced perceived pain (70-80%) in PFPS subjects. Although patellar taping did not influence leg press force (P > 0.05), it increased the VMO activity and decreased the VL activity in PFPS subjects but had the opposite effect in healthy subjects. The findings suggest that taping the patella medially can contribute positively to PFPS rehabilitation. Because the medial glide and placebo taping conditions had similar effects, it is proposed that the benefits of patellar taping are not due to a change in patellar position but rather due to enhanced support of the patellofemoral ligaments and/or pain modulation via cutaneous stimulation.     

A second KRT71 allele in curly coated dogs

Major characteristics of coat variation in dogs can be explained by variants in only a few genes. Until now, only one missense variant in the KRT71 gene, p.Arg151Trp, has been reported to cause curly hair in dogs. However, this variant does not explain the curly coat in all breeds as the mutant ¹⁵¹Trp allele, for example, is absent in Curly Coated Retrievers. We sequenced the genome of a Curly Coated Retriever at 22× coverage and searched for variants in the KRT71 gene. Only one protein‐changing variant was present in a homozygous state in the Curly Coated Retriever and absent or present in a heterozygous state in 221 control dogs from different dog breeds. This variant, NM_001197029.1:c.1266_1273delinsACA, was an indel variant in exon 7 that caused a frameshift and an altered and probably extended C‐terminus of the KRT71 protein NP_001183958.1:p.(Ser422ArgfsTer?). Using Sanger sequencing, we found that the variant was fixed in a cohort of 125 Curly Coated Retrievers and segregating in five of 14 additionally tested breeds with a curly or wavy coat. KRT71 variants cause curly hair in humans, mice, rats, cats and dogs. Specific KRT71 variants were further shown to cause alopecia. Based on this knowledge from other species and the predicted molecular consequence of the newly identified canine KRT71 variant, it is a compelling candidate causing a second curly hair allele in dogs. It might cause a slightly different coat phenotype than the previously published p.Arg151Trp variant and could potentially be associated with follicular dysplasia in dogs.     

Association between COMT SNP variation and timidity in Golden and Labrador Retrievers

Timidity in dogs is a trait with high heritability. However, the relevant genetic factors and markers associated with this condition are largely unknown. The function of the catechol‐O‐methyl transferase (COMT) gene has been found to be associated with human fearful or anxious emotions, and the COMT:p.Val158Met polymorphism locus is significantly related to anxious behavior. In the present study, the correlation between timidity and four single nucleotide polymorphism (SNP) variations (C.‐1666C>G c.39A>G, c.216G>A, c.482G>A) of the COMT gene was investigated in dogs. The evaluation was based on the dog courage assessment assay and a genotype and haplotype analysis in Labrador Retrievers (LR) and Golden Retrievers (GR). The principal components analysis factor structure of the courage phenotype was invariant between LR and GR. Sex, breed and age had no statistically significant effect on the timidity of the dogs. All SNP loci detected were in Hardy–Weinberg equilibrium. The c.39A>G locus was removed in the subsequent association analysis due to the significant difference between LR and GR in genotype distributions. Intriguingly, the genotypes and haplotypes of the COMT gene were significantly and highly correlated with the timidity of LR and GR. The A alleles of the COMT:c.216G>A and c.482G>A loci appeared to play a dominant role in the timid behavior of the dogs. This result supports and broadens the warrior/worrier hypothesis and will have important implications for the understanding of the evolution of temperament in dogs. Additionally, the results provide predictive genetic markers for temperament in dogs.     

The biomechanical function of the patellar tendon during in-vivo weight-bearing flexion

Few studies have investigated the function of the patellar tendon in-vivo. This study quantified the three-dimensional (3D) kinematics of the patellar tendon during weight-bearing flexion. Eleven subjects were imaged using magnetic resonance (MR). Sagittal plane images were outlined to create a 3D model of the patella, tibia, and femur and included the attachment sites of the patellar tendon. Each attachment site was divided into central, medial, and lateral thirds. Next, the subjects were imaged using fluoroscopy from two orthogonal directions while performing a single-leg lunge. The models and fluoroscopic images were used to reproduce the motion of the patella, tibia, and femur. The apparent elongation, sagittal plane angle, and coronal plane angle of each third of the patellar tendon were measured from the relative motion of the attachment sites. All three portions of the patellar tendon deformed similarly with flexion. The length of the patellar tendon significantly from full extension to 30 degrees . From 30 degrees -110 degrees , no significant change in the length of the patellar tendon was observed. The patellar tendon was oriented anteriorly at flexion angles less than 60 degrees and posteriorly thereafter. From full extension to 60 degrees , the medial orientation of the patellar tendon decreased significantly with flexion. These data may have important implications for anterior cruciate ligament reconstruction using patellar tendon autografts and for the design of rehabilitation regimens for patients of patellar tendon repair.     

A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis

Hereditary nasal parakeratosis (HNPK), described in the Labrador Retriever breed, is a monogenic autosomal recessive disorder that causes crusts and fissures on the nasal planum of otherwise healthy dogs. Our group previously showed that this genodermatosis may be caused by a missense variant located in the SUV39H2 gene encoding a histone 3 lysine 9 methyltransferase, a chromatin modifying enzyme with a potential role in keratinocyte differentiation. In the present study, we investigated a litter of Greyhounds in which six out of eight puppies were affected with parakeratotic lesions restricted to the nasal planum. Clinically and histologically, the lesions were comparable to HNPK in Labrador Retrievers. Whole genome sequencing of one affected Greyhound revealed a 4‐bp deletion at the 5′‐end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5′‐splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non‐affected littermates were heterozygous. Genotyping of a larger cohort of Greyhounds revealed that the variant is segregating in the breed and that this breed might benefit from genetic testing to avoid carrier × carrier matings.     

A new in vivo technique for determination of femoro-tibial and femoro-patellar 3D kinematics in total knee arthroplasty

Aim was to develop an in vivo technique which allows determination of femoro-tibial and of femoro-patellar 3D-kinematics in TKA simultaneously. The knees of 20 healthy volunteers and of eight patients with TKA (PCR, rotating platform) were investigated. Kinematics analysis was performed in an open MR-system at different flexion angles with external loads being applied. The TKA components were identified using a 3D-fitting technique, which allows an automated 3D-3D-registration of the TKA. Femoro-patellar and femoro-tibial 3D-kinematics were analyzed by image postprocessing. The validity of the postprocessing technique demonstrated a coefficient of determination of 0.98 for translation and of 0.97 for rotation. The reproducibility yielded a coefficient of variation (CV%) for patella kinematics between 0.17% (patello-femoral angle) and 6.8% (patella tilt). The femoro-tibial displacement also showed a high reproducibility with CV% of 4.0% for translation and of 7.1% for rotation. While in the healthy knees the typical screw-home mechanism was observed, a paradoxical anterior translation of the femur relative to the tibia combined with an external rotation occurred after TKA. Fifty percent of the TKA's experienced a condylar lift-off of >1mm predominately on the medial side. Regarding patellar kinematics significant changes were found in both planes in TKA with an increased patella height in the sagittal plane and patella tilt and shift in the transversal plane. The results demonstrate that the presented 3D MR-open based method is highly reproducible and valid for image acquisition and postprocessing and provides--for the first time--in vivo data of 3D-kinematics of the tibio-femoral and simultaneously of the patello-femoral joint during knee flexion.     

Extent of linkage disequilibrium in large-breed dogs: chromosomal and breed variation

The aim of this study was to better define the extent of linkage disequilibrium (LD) in populations of large-breed dogs and its variation by breed and chromosomal region. Understanding the extent of LD is a crucial component for successful utilization of genome-wide association studies and allows researchers to better define regions of interest and target candidate genes. Twenty-four Golden Retriever dogs, 28 Rottweiler dogs, and 24 Newfoundland dogs were genotyped for single-nucleotide polymorphism (SNP) data using a high-density SNP array. LD was calculated for all autosomes using Haploview. Decay of the squared correlation coefficient (r ²) was plotted on a per-breed and per-chromosome basis as well as in a genome-wide fashion. The point of 50 % decay of r ² was used to estimate the difference in extent of LD between breeds. Extent of LD was significantly shorter for Newfoundland dogs based upon 50 % decay of r ² data at a mean of 344 kb compared to Golden Retriever and Rottweiler dogs at 715 and 834 kb, respectively (P < 0.0001). Notable differences in LD by chromosome were present within each breed and not strictly related to the length of the corresponding chromosome. Extent of LD is breed and chromosome dependent. To our knowledge, this is the first report of SNP-based LD for Newfoundland dogs, the first report based on genome-wide SNPs for Rottweilers, and an almost tenfold improvement in marker density over previous genome-wide studies of LD in Golden Retrievers.     

Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.     

In vivo patellar tracking induced by individual quadriceps components in individuals with patellofemoral pain

Patellofemoral pain is a common knee disorder with a multi-factorial etiology related to abnormal patellar tracking. Our hypothesis was that the pattern of three-dimensional rotation and translation of the patella induced by selective activation of individual quadriceps components would differ between subjects with patellofemoral pain and healthy subjects. Nine female subjects with patellofemoral pain and seven healthy female subjects underwent electrical stimulation to selectively activate individual quadriceps components (vastus medialis obliquus, VMO; vastus medialis lateralis, VML; vastus lateralis, VL) with the knee at 0° and 20° flexion, while three-dimensional patellar tracking was recorded. Normalized direction of rotation and direction of translation characterized the relative amplitudes of each component of patellar movement. VMO activation in patellofemoral pain caused greater medial patellar rotation (distal patellar pole rotates medially in frontal plane) at both knee positions (p<0.01), and both VMO and VML activation caused increased anterior patellar translation (p<0.001) in patellofemoral pain compared to healthy subjects at 20° knee flexion. VL activation caused more lateral patellar translation (p<0.001) in patellofemoral pain compared to healthy subjects. In healthy subjects the 3-D mechanical action of the VMO is actively modulated with knee flexion angle while such modulation was not observed in PFP subjects. This could be due to anatomical differences in the VMO insertion on the patella and medial quadriceps weakness. Quantitative evaluation of the influence of individual quadriceps components on patellar tracking will aid understanding of the knee extensor mechanism and provide insight into the etiology of patellofemoral pain.     

Intervertebral disc disease in Dachshunds radiographically screened for intervertebral disc calcifications

Background

Intervertebral disc disease (IDD) is a very common neurological disease, Dachshunds being the breed most often affected. In this breed, IDD has a hereditary background and is associated with intervertebral disc calcification (IDC), an indicator of severe intervertebral disc degeneration. In Finland, spinal radiography is used, when screening for IDC before breeding Dachshunds. We evaluated the association between IDC and IDD in Finnish Dachshunds radiographically screened for IDC.A questionnaire was sent to owners of 193 radiographically screened Dachshunds aged at least ten years. Clinical signs indicative of IDD were compared with IDC grade (grade 0?=?no calcifications, grade 1?=?1 – 2 calcifications, grade 2?=?3 – 4 calcifications and grade 3?=?5 or more calcifications) and with age at the time of the radiographic examination. The diagnosis of IDD was confirmed by a veterinarian.

Results

IDD was common in the study population with 31% of dogs being affected. IDD and IDC were clearly connected (P?<?0.001); IDD was rare in dogs with no calcifications (grade 0) and common in dogs with severe IDC (grade 3). The IDC grade was strongly positively associated with frequency of back pain periods (P?<?0.001), and dogs with IDC grade 3 had frequent periods of pain. Reluctance to jump onto a sofa had a strong positive association with back pain. No association existed between age of the dog at the time of the radiographic examination and clinical signs indicative of IDD.

Conclusions

Radiographically detected IDC and IDD are common in Finnish Dachshunds and are strongly associated with one another. Spinal radiography is an appropriate screening tool for breeders attempting to diminish IDC and IDD in Dachshunds. A breeding program that screens dogs and selects against IDC can be expected to reduce the occurrence of IDD in future. Twenty-four to 48 months of age is a suitable age for screening.

     

Validation of DNA test for hip dysplasia failed in Danish Labrador Retrievers

Canine hip dysplasia is characterized by poor hip joint conformation and laxity. The disease is a complex trait influenced by both genetics and environment. Diagnosis and quantification of hip dysplasia are performed by radiographic examination of the hip joint and the diagnosis is used for making breeding decisions in many breeds. A prognostic genetic test (the Dysgen test) based on seven associated SNPs has been developed in a study based on Spanish Labrador Retrievers. In our study this test has been evaluated in 39 Danish Labrador Retrievers with known radiographic hip score: 14 with hip dysplasia (grade D or E) and 25 without hip dysplasia (grade A or B). There was no significant correlation between the Dysgen test results and the radiographic hip status (P = 0.3203) in these dogs, indicating that Dysgen test results obtained for Danish Labrador Retrievers have no prognostic value.     

Retrospective Analysis for Genetic Improvement of Hip Joints of Cohort Labrador Retrievers in the United States: 1970–2007

Background

Canine Hip Dysplasia (CHD) is a common inherited disease that affects dog wellbeing and causes a heavy financial and emotional burden to dog owners and breeders due to secondary hip osteoarthritis. The Orthopedic Foundation for Animals (OFA) initiated a program in the 1960''s to radiograph hip and elbow joints and release the OFA scores to the public for breeding dogs against CHD. Over last four decades, more than one million radiographic scores have been released.

Methodology/Principal Findings

The pedigrees in the OFA database consisted of 258,851 Labrador retrievers, the major breed scored by the OFA (25% of total records). Of these, 154,352 dogs had an OFA hip score reported between 1970 and 2007. The rest of the dogs (104,499) were the ancestors of the 154,352 dogs to link the pedigree relationships. The OFA hip score is based on a 7-point scale with the best ranked as 1 (excellent) and the worst hip dysplasia as 7. A mixed linear model was used to estimate the effects of age, sex, and test year period and to predict the breeding value for each dog. Additive genetic and residual variances were estimated using the average information restricted maximum likelihood procedure. The analysis also provided an inbreeding coefficient for each dog. The hip scores averaged 1.93 (±SD = 0.59) and the heritability was 0.21. A steady genetic improvement has accrued over the four decades. The breeding values decreased (improved) linearly. By the end of 2005, the total genetic improvement was 0.1 units, which is equivalent to 17% of the total phenotypic standard deviation.

Conclusion/Significance

A steady genetic improvement has been achieved through the selection based on the raw phenotype released by the OFA. As the heritability of the hip score was on the low end (0.21) of reported ranges, we propose that selection based on breeding values will result in more rapid genetic improvement than breeding based on phenotypic selection alone.     

Correlation between trochlear groove depth and patellar position during open and closed kinetic chain exercises in subjects with anterior knee pain

The purpose of this study was to correlate the trochlear shape and patellar tilt angle and lateral patellar displacement at rest and maximal voluntary isometric contraction (MVIC) exercises during open (OKC) and closed kinetic chain (CKC) in subjects with and without anterior knee pain. Subjects were all women, 20 who were clinically healthy and 19 diagnosed with anterior knee pain. All subjects were evaluated and subjected to magnetic resonance exams during OKC and CKC exercise with the knee placed at 15, 30, and 45 degrees of flexion. The parameters evaluated were sulcus angle, patellar tilt angle and patellar displacement using bisect offset. Pearson's r coefficient was used, with p < .05. Our results revealed in knee pain group during CKC and OKC at 15 degrees that the increase in the sulcus angle is associated with a tilt increase and patellar lateral displacement. Comparing sulcus angle, patellar tilt angle and bisect offset values between MVIC in OKC and CKC in the knee pain group, it was observed that patellar tilt angle increased in OKC only with the knee flexed at 30 degrees. Based on our results, we conclude that reduced trochlear depth is correlated with increased lateral patellar tilt and displacement during OKC and CKC at 15 degrees of flexion in people with anterior knee pain. By contrast, 30 degrees of knee flexion in CKC is more recommended in rehabilitation protocols because the patella was more stable than in other positions.