Multivariate genome-wide association analysis identifies novel and relevant variants associated with anterior cruciate ligament rupture risk in the dog model

Baker, Louise; Rosa, Guilherme J. M.; Hao, Zhengling; Piazza, Alexander M; Hoffman, Christopher; Binversie, Emily E.; Sample, Susannah J.; Muir, Peter

doi:10.1186/s12863-018-0626-7

Cited by 16 publications

(28 citation statements)

References 84 publications

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“…SNPs with the largest mean difference were considered to be the most likely associated with ACL rupture (Hajiloo et al 2013). The number of genetic variants believed to affect ACL rupture in dogs is unknown, though there are likely hundreds to thousands of non-null effect SNPs (Baker et al 2017;Baker et al 2018). Therefore, prediction performance of each model was assessed at several SNP inclusion thresholds from 5 to 15,000 SNPs.…”

Section: Snp Selectionmentioning

confidence: 99%

Bayesian and Machine Learning Models for Genomic Prediction of Anterior Cruciate Ligament Rupture in the Canine Model

Baker

Momen

Chan

et al. 2020

G3 Genes|Genomes|Genetics

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Anterior cruciate ligament (ACL) rupture is a common, debilitating condition that leads to early-onset osteoarthritis and reduced quality of human life. ACL rupture is a complex disease with both genetic and environmental risk factors. Characterizing the genetic basis of ACL rupture would provide the ability to identify individuals that have high genetic risk and allow the opportunity for preventative management. Spontaneous ACL rupture is also common in dogs and shows a similar clinical presentation and progression. Thus, the dog has emerged as an excellent genomic model for human ACL rupture. Genome-wide association studies (GWAS) in the dog have identified a number of candidate genetic variants, but research in genomic prediction has been limited. In this analysis, we explore several Bayesian and machine learning models for genomic prediction of ACL rupture in the Labrador Retriever dog. Our work demonstrates the feasibility of predicting ACL rupture from SNPs in the Labrador Retriever model with and without consideration of non-genetic risk factors. Genomic prediction including non-genetic risk factors approached clinical relevance using multiple linear Bayesian and non-linear models. This analysis represents the first steps towards development of a predictive algorithm for ACL rupture in the Labrador Retriever model. Future work may extend this algorithm to other high-risk breeds of dog. The ability to accurately predict individual dogs at high risk for ACL rupture would identify candidates for clinical trials that would benefit both veterinary and human medicine.

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Section: Snp Selectionmentioning

confidence: 99%

Bayesian and Machine Learning Models for Genomic Prediction of Anterior Cruciate Ligament Rupture in the Canine Model

Baker

Momen

Chan

et al. 2020

G3 Genes|Genomes|Genetics

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“…CrCL ruptures continue to be a disease that negatively affects the lives of dogs who share our homes, as well as in working and sporting breeds. Advancing technology and facilities have reduced the costs of tests for the diagnosis of genetic and environmental components leading to CrCL rupture [10,11]. Although some studies [12] have reported a direct proportion between the incidence of CrCL rupture and increasing age, an increase in body weight and neutering rate have caused this disease to appear at an earlier age [13].…”

Section: Discussionmentioning

confidence: 99%

Clinical results of triple tibial osteotomy treatment in cranial cruciateligament-deficient dogs

Yaprakci¹,

Saritaş²

2020

Turk J Vet Anim Sci

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This study examined the TTO method to share the treatment results on dogs and contribute to the current scientific literature in Turkey. 2. Materials and methods Herein, 7 dogs diagnosed with CrCL deficiency were assessed using clinical and radiological examinations. The study was performed at the Animal Health Management and Research Hospital of Afyon Kocatepe University. Dogs were chosen from those that qualified for surgical treatment for CrCL rupture. They varied in weight, breed, age, and sex. Ethical permission was granted by the Afyon Kocatepe University Ethical Commission for Animal Experiments under verification number 49533702/105. 2.1. Preoperative planning X-rays were taken at a 135° knee joint mediolateral projection by extending the joint. Simultaneously, ventrodorsal hip-extended radiographs and additional possible diseases were examined. The images were stored and evaluated using computer software for wedge angle (WA) calculations. X-rays were evaluated for the angle measurement between the patellar ligament and tibial Abstract: Canine cranial cruciate ligament ruptures have become common with improved nutrition and nonselective breeding strategies. This study assessed 7 dogs of various breeds and ages with the diagnosis of cranial cruciate ligament ruptures. The triple tibial osteotomy (TTO) method was used to treat the rupture. All of the dogs were admitted to the clinic for varying degrees of lameness. Diagnosis was confirmed using both clinical and radiologic examinations. Body weights of the dogs were between 12 and 65 kg. Informed consent was given by the owners prior to surgery. Postoperatively, early evaluations were made using periodic radiographs and clinical examinations, but long-term evaluations were performed by phone interviews due to economic and other limitations by the owners. The TTO operation method was completed successfully in all of the cases and only with Case 5 was a major complication encountered (tibial tuberosity fracture from the distal pivot hole). In 3 cases, the minor complication of wound contamination occurred due to poor wound care by the owners of the dogs. Owners were advised to restrict mobilization for a week following cast removal. Early, mid-, and long-term postoperative results showed functional recovery in all of the cases. All of the dogs returned to their pretrauma lives and those that had chronic symptoms had a significant increase in their mobility when compared to their previous states after cranial cruciate ligament rupture.

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“…2014a, 2014b; Baker et al . 2017, 2018). The CCLR heritability estimate calculated for LRs using SNP genotype data was 0.493 (Baker et al .…”

Section: Program Heritability All Dogs (N = 333) Heritability With Sementioning

confidence: 99%

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

et al. 2020

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Summary 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.

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Multivariate genome-wide association analysis identifies novel and relevant variants associated with anterior cruciate ligament rupture risk in the dog model

Cited by 16 publications

References 84 publications

Bayesian and Machine Learning Models for Genomic Prediction of Anterior Cruciate Ligament Rupture in the Canine Model

Bayesian and Machine Learning Models for Genomic Prediction of Anterior Cruciate Ligament Rupture in the Canine Model

Clinical results of triple tibial osteotomy treatment in cranial cruciateligament-deficient dogs

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

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