SNP-based heritability and genetic architecture of cranial cruciate ligament rupture in Labrador Retrievers.
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ABSTRACT:
SUBMITTER: Cook SR
PROVIDER: S-EPMC7492375 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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SNP-based heritability and genetic architecture of cranial cruciate ligament rupture in Labrador Retrievers.
Cook S R SR Conzemius M G MG McCue M E ME Ekenstedt K J KJ
Animal genetics 20200722 5
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 ...[more]
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Project description:We recently reported that a conformation score derived from the tibial plateau angle (TPA) and the femoral anteversion angle (FAA), best discriminates limbs predisposed to, or affected by cranial cruciate ligament disease (CCLD), from those that are at low risk for CCLD. The specificity and sensitivity of this score were high enough to support further investigations toward its use for large-scale screening of dogs by veterinarians. The next step, which is the objective of the current study, is to determine inter-observer variability of that CCLD score in a large population of Labrador Retrievers. A total of 167 Labradors were enrolled in this cross-sectional study. Limbs of normal dogs over 6 years of age with no history of CCLD were considered at low risk for CCLD. Limbs of dogs with CCLD were considered at high risk for CCLD. Tibial plateau and femoral anteversion angles were measured independently by two investigators to calculate a CCLD score for each limb. Kappa statistics were used to determine the extent of agreement between investigators. Pearson's correlation and intraclass coefficients were calculated to evaluate the correlation between investigators and the relative contribution of each measurement to the variability of the CCLD score.The correlation between CCLD scores calculated by investigators was good (correlation coefficient = 0.68 p < 0.0001). However, interobserver agreement with regards to the predicted status of limbs was fair (kappa value = 0.28), with 37% of limbs being assigned divergent classifications. Variations in CCLD scores correlated best with those of TPA, which was the least consistent parameter between investigators. Absolute interobserver differences were two times greater for FAAs (4.19° ± 3.15) than TPAs (2.23° ± 1.91).The reproducibility of the CCLD score between investigators is fair, justifying caution when interpreting individual scores. Future studies should focus on improving the reproducibility of TPA and FAA measurements, as strategies to improve the agreement between CCLD scores.
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Project description:Tibial Tuberosity Advancement (TTA) is a surgical technique based on a linear osteotomy that determines a cranial advancement of the tibial tuberosity in patients suffering from cranial cruciate ligament rupture (CCL). The aim is to neutralize the cranial tibial thrust (CTT) and to reach a 90° angle between the patellar tendon and the tibial plateau with a physiological knee extension of 135°. In our study, a Ti6AI4V ELI (Titanium Aluminium Vanadium) titanium scaffold for the Porous TTA, with excellent properties of osteointegration and osteoconduction when subjected to cyclic loading has been adopted. Based on the previous scientific work on an ovine model, the use of this type of porous scaffolds has subverted the previous models. Scaffold production technology is based on direct mechanical manufacturing called Electron Beam Melting (EBM). For this study, 41 dogs, different breeds, medium-large size, weighing between 10 and 80 kg, aged between 1 and 13 years, were enrolled. The inclusion criteria were based on clinical evaluations (different gaits), drawer test and tibial compression, LOAD score (Liverpool Osteoarthritis in Dogs questionnaire), radiographic diagnosis in sedation with a 135° positioning of the joint and baropodometric investigations (Stance Analyzer). The results show that Porous TTA is an excellent method for functional recovery of the knee joint following the partial and total rupture of the CCL.
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Project description:BackgroundCranial cruciate ligament rupture (CCLR) results from a multifactorial degenerative process that leads to rupture of the ligament. Vector-borne pathogens (VBP) in dogs can induce joint disease but their role in CCLR has not been previously investigated. The aim of the present work is to evaluate the prevalence of VBP in dogs with CCLR.MethodsThis was a prospective study that included 46 dogs presented for CCLR surgical treatment and 16 control dogs euthanized for diseases unrelated to the joints. Specimens collected included blood, synovial fluid, and synovial membrane biopsy. Pathogen testing consisted of serology for Leishmania infantum (quantitative ELISA), Ehrlichia canis/ewingii, Borrelia burgdorferi, Anaplasma phagocytophilum/platys, and Dirofilaria immitis (4DX IDEXX test), and PCR for L. infantum, Ehrlichia/Anaplasma spp., Bartonella spp., piroplasms (Babesia spp. and Theileria spp.), and filariae (D. immitis, Dirofilaria repens, Acanthocheilonema dracunculoides, Acanthocheilonema reconditum, and Cercopithifilaria spp.) on both EDTA-whole blood (EB) and synovial fluid (SF) samples. SF cytology and histopathological evaluation of synovial membrane were also performed.ResultsThe prevalence of VBP was 19.6% in the CCLR group and 18.8% in the control group, with no statistical difference among them. The presence of synovitis was not more frequent in CCLR dogs (45.6%) than in control dogs (43.7%). Lymphoplasmacytic infiltration was the most common inflammatory pattern detected in the joints of both groups of dogs.ConclusionsThis study failed to demonstrate a role of canine VBP in CCLR or the presence or different pattern of joint inflammation in pathogen-positive dogs.
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