Genomic Prediction of Two Complex Orthopedic Traits Across Multiple Pure and Mixed Breed Dogs

Canine hip dysplasia (CHD) and rupture of the cranial cruciate ligament (RCCL) are two complex inherited orthopedic traits of dogs. These two traits may occur concurrently in the same dog. Genomic prediction of these two diseases would benefit veterinary medicine, the dog’s owner, and dog breeders because of their high prevalence, and because both traits result in painful debilitating osteoarthritis in affected joints. In this study, 842 unique dogs from 6 breeds with hip and stifle phenotypes were genotyped on a customized Illumina high density 183 k single nucleotide polymorphism (SNP) array and also analyzed using an imputed dataset of 20,487,155 SNPs. To implement genomic prediction, two different statistical methods were employed: Genomic Best Linear Unbiased Prediction (GBLUP) and a Bayesian method called BayesC. The cross-validation results showed that the two methods gave similar prediction accuracy (r = 0.3–0.4) for CHD (measured as Norberg angle) and RCCL in the multi-breed population. For CHD, the average correlation of the AUC was 0.71 (BayesC) and 0.70 (GBLUP), which is a medium level of prediction accuracy and consistent with Pearson correlation results. For RCCL, the correlation of the AUC was slightly higher. The prediction accuracy of GBLUP from the imputed genotype data was similar to the accuracy from DNA array data. We demonstrated that the genomic prediction of CHD and RCCL with DNA array genotype data is feasible in a multiple breed population if there is a genetic connection, such as breed, between the reference population and the validation population. Albeit these traits have heritability of about one-third, higher accuracy is needed to implement in a natural population and predicting a complex phenotype will require much larger number of dogs within a breed and across breeds. It is possible that with higher accuracy, genomic prediction of these orthopedic traits could be implemented in a clinical setting for early diagnosis and treatment, and the selection of dogs for breeding. These results need continuous improvement in model prediction through ongoing genotyping and data sharing. When genomic prediction indicates that a dog is susceptible to one of these orthopedic traits, it should be accompanied by clinical and radiographic screening at an acceptable age with appropriate follow-up.

Download Full-text

PSXII-22 Genomic prediction accuracy for feed efficiency related traits using different pseudo-phenotypes, prediction and validation methods in Nellore cattle

Journal of Animal Science ◽

10.1093/jas/skaa278.446 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 245-246

Author(s):

Cláudio U Magnabosco ◽

Fernando Lopes ◽

Valentina Magnabosco ◽

Raysildo Lobo ◽

Leticia Pereira ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Genomic Prediction ◽

Feed Efficiency ◽

Prediction Accuracy ◽

Body Weight Gain ◽

Prediction Methods ◽

Genomic Breeding ◽

Validation Population ◽

Nellore Cattle

Abstract The aim of the study was to evaluate prediction methods, validation approaches and pseudo-phenotypes for the prediction of the genomic breeding values of feed efficiency related traits in Nellore cattle. It used the phenotypic and genotypic information of 4,329 and 3,594 animals, respectively, which were tested for residual feed intake (RFI), dry matter intake (DMI), feed efficiency (FE), feed conversion ratio (FCR), residual body weight gain (RG), and residual intake and body weight gain (RIG). Six prediction methods were used: ssGBLUP, BayesA, BayesB, BayesCπ, BLASSO, and BayesR. Three validation approaches were used: 1) random: where the data was randomly divided into ten subsets and the validation was done in each subset at a time; 2) age: the division into the training (2010 to 2016) and validation population (2017) were based on the year of birth; 3) genetic breeding value (EBV) accuracy: the data was split in the training population being animals with accuracy above 0.45; and validation population those below 0.45. We checked the accuracy and bias of genomic value (GEBV). The results showed that the GEBV accuracy was the highest when the prediction is obtained with ssGBLUP (0.05 to 0.31) (Figure 1). The low heritability obtained, mainly for FE (0.07 ± 0.03) and FCR (0.09 ± 0.03), limited the GEBVs accuracy, which ranged from low to moderate. The regression coefficient estimates were close to 1, and similar between the prediction methods, validation approaches, and pseudo-phenotypes. The cross-validation presented the most accurate predictions ranging from 0.07 to 0.037. The prediction accuracy was higher for phenotype adjusted for fixed effects than for EBV and EBV deregressed (30.0 and 34.3%, respectively). Genomic prediction can provide a reliable estimate of genomic breeding values for RFI, DMI, RG and RGI, as to even say that those traits may have higher genetic gain than FE and FCR.

Download Full-text

A study of Genomic Prediction across Generations of Two Korean Pig Populations

Animals ◽

10.3390/ani9090672 ◽

2019 ◽

Vol 9 (9) ◽

pp. 672 ◽

Cited By ~ 1

Author(s):

Beatriz Castro Dias Castro Dias Cuyabano ◽

Hanna Wackel ◽

Donghyun Shin ◽

Cedric Gondro

Keyword(s):

Genomic Prediction ◽

Prediction Accuracy ◽

Reference Population ◽

Relevant Information ◽

Production Traits ◽

Genomic Evaluation ◽

Genomic Breeding ◽

Breeding Values ◽

The Relationship ◽

Dense Marker

Genomic models that incorporate dense marker information have been widely used for predicting genomic breeding values since they were first introduced, and it is known that the relationship between individuals in the reference population and selection candidates affects the prediction accuracy. When genomic evaluation is performed over generations of the same population, prediction accuracy is expected to decay if the reference population is not updated. Therefore, the reference population must be updated in each generation, but little is known about the optimal way to do it. This study presents an empirical assessment of the prediction accuracy of genomic breeding values of production traits, across five generations in two Korean pig breeds. We verified the decay in prediction accuracy over time when the reference population was not updated. Additionally we compared the prediction accuracy using only the previous generation as the reference population, as opposed to using all previous generations as the reference population. Overall, the results suggested that, although there is a clear need to continuously update the reference population, it may not be necessary to keep all ancestral genotypes. Finally, comprehending how the accuracy of genomic prediction evolves over generations within a population adds relevant information to improve the performance of genomic selection.

Download Full-text

Genomic prediction of weight and wool traits in a multi-breed sheep population

Animal Production Science ◽

10.1071/an13129 ◽

2014 ◽

Vol 54 (5) ◽

pp. 544 ◽

Cited By ~ 4

Author(s):

N. Moghaddar ◽

A. A. Swan ◽

J. H. J. van der Werf

Keyword(s):

Genomic Prediction ◽

Pearson Correlation ◽

Reference Population ◽

Breeding Value ◽

Genomic Relationship Matrix ◽

Relationship Matrix ◽

Sheep Population ◽

Australian Sheep ◽

Estimated Breeding Value ◽

Breed Sheep

The objective of this study was to predict the accuracy of genomic prediction for 26 traits, including weight, muscle, fat, and wool quantity and quality traits, in Australian sheep based on a large, multi-breed reference population. The reference population consisted of two research flocks, with the main breeds being Merino, Border Leicester (BL), Poll Dorset (PD), and White Suffolk (WS). The genomic estimated breeding value (GEBV) was based on GBLUP (genomic best linear unbiased prediction), applying a genomic relationship matrix calculated from the 50K Ovine SNP chip marker genotypes. The accuracy of GEBV was evaluated as the Pearson correlation coefficient between GEBV and accurate estimated breeding value based on progeny records in a set of genotyped industry animals. The accuracies of weight traits were relatively low to moderate in PD and WS breeds (0.11–0.27) and moderate to relatively high in BL and Merino (0.25–0.63). The accuracy of muscle and fat traits was moderate to relatively high across all breeds (between 0.21 and 0.55). The accuracy of GEBV of yearling and adult wool traits in Merino was, on average, high (0.33–0.75). The results showed the accuracy of genomic prediction depends on trait heritability and the effective size of the reference population, whereas the observed GEBV accuracies were more related to the breed proportions in the multi-breed reference population. No extra gain in within-breed GEBV accuracy was observed based on across breed information. More investigations are required to determine the precise effect of across-breed information on within-breed genomic prediction.

Download Full-text

Genetic architecture and genomic prediction accuracy of apple quantitative traits across environments

10.1101/2021.11.29.470309 ◽

2021 ◽

Author(s):

Michaela Jung ◽

Beat Keller ◽

Morgane Roth ◽

Maria Jose Aranzana ◽

Annemarie Auwerkerken ◽

...

Keyword(s):

Genomic Prediction ◽

Prediction Accuracy ◽

Genetic Architecture ◽

Quantitative Traits ◽

Prediction Models ◽

Phenotypic Variability ◽

Reference Population ◽

Genomic Study ◽

Genomic Tools ◽

Breeding Efficiency

Implementation of genomic tools is desirable to increase the efficiency of apple breeding. The apple reference population (apple REFPOP) proved useful for rediscovering loci, estimating genomic prediction accuracy, and studying genotype by environment interactions (GxE). Here we show contrasting genetic architecture and genomic prediction accuracies for 30 quantitative traits across up to six European locations using the apple REFPOP. A total of 59 stable and 277 location-specific associations were found using GWAS, 69.2% of which are novel when compared with 41 reviewed publications. Average genomic prediction accuracies of 0.18-0.88 were estimated using single-environment univariate, single-environment multivariate, multi-environment univariate, and multi-environment multivariate models. The GxE accounted for up to 24% of the phenotypic variability. This most comprehensive genomic study in apple in terms of trait-environment combinations provided knowledge of trait biology and prediction models that can be readily applied for marker-assisted or genomic selection, thus facilitating increased breeding efficiency.

Download Full-text

Improving Genomic Prediction of Crossbred and Purebred Dairy Cattle

Frontiers in Genetics ◽

10.3389/fgene.2020.598580 ◽

2020 ◽

Vol 11 ◽

Author(s):

Majid Khansefid ◽

Michael E. Goddard ◽

Mekonnen Haile-Mariam ◽

Kon V. Konstantinov ◽

Chris Schrooten ◽

...

Keyword(s):

Genomic Prediction ◽

Milk Fat ◽

Prediction Accuracy ◽

Reference Population ◽

High Density ◽

Crossbred Cows ◽

Mixed Breed ◽

Best Linear Unbiased ◽

Custom Panel ◽

Accuracy Of Prediction

This study assessed the accuracy and bias of genomic prediction (GP) in purebred Holstein (H) and Jersey (J) as well as crossbred (H and J) validation cows using different reference sets and prediction strategies. The reference sets were made up of different combinations of 36,695 H and J purebreds and crossbreds. Additionally, the effect of using different sets of marker genotypes on GP was studied (conventional panel: 50k, custom panel enriched with, or close to, causal mutations: XT_50k, and conventional high-density with a limited custom set: pruned HDnGBS). We also compared the use of genomic best linear unbiased prediction (GBLUP) and Bayesian (emBayesR) models, and the traits tested were milk, fat, and protein yields. On average, by including crossbred cows in the reference population, the prediction accuracies increased by 0.01–0.08 and were less biased (regression coefficient closer to 1 by 0.02–0.16), and the benefit was greater for crossbreds compared to purebreds. The accuracy of prediction increased by 0.02 using XT_50k compared to 50k genotypes without affecting the bias. Although using pruned HDnGBS instead of 50k also increased the prediction accuracy by about 0.02, it increased the bias for purebred predictions in emBayesR models. Generally, emBayesR outperformed GBLUP for prediction accuracy when using 50k or pruned HDnGBS genotypes, but the benefits diminished with XT_50k genotypes. Crossbred predictions derived from a joint pure H and J reference were similar in accuracy to crossbred predictions derived from the two separate purebred reference sets and combined proportional to breed composition. However, the latter approach was less biased by 0.13. Most interestingly, using an equalized breed reference instead of an H-dominated reference, on average, reduced the bias of prediction by 0.16–0.19 and increased the accuracy by 0.04 for crossbred and J cows, with a little change in the H accuracy. In conclusion, we observed improved genomic predictions for both crossbreds and purebreds by equalizing breed contributions in a mixed breed reference that included crossbred cows. Furthermore, we demonstrate, that compared to the conventional 50k or high-density panels, our customized set of 50k sequence markers improved or matched the prediction accuracy and reduced bias with both GBLUP and Bayesian models.

Download Full-text

Determination of Graft Forces for Cranial Cruciate Ligament Reconstruction in the Dog

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1632524 ◽

1996 ◽

Vol 09 (04) ◽

pp. 165-171 ◽

Cited By ~ 1

Author(s):

D. A. Hulse ◽

M. R. Slater ◽

J. F. Hunter ◽

W. A. Hyman ◽

B. A. Shelley

Keyword(s):

Degrees Of Freedom ◽

Cruciate Ligament ◽

Insertion Site ◽

Graft Fixation ◽

Flexion Angle ◽

Patellar Ligament ◽

Graft Material ◽

Test Apparatus ◽

Cranial Cruciate Ligament ◽

Tibial Insertion

SummaryA test apparatus that allowed the stifle to move in five degrees of freedom was used to determine the effect of graft location, graft preload, and flexion angle at the time of graft fixation on the tensile graft forces experienced by a replacement graft material used to simulate reconstruction of the cranial cruciate ligament deficient stifle. Two graft locations (tibial insertion site of the patellar ligament and tibial insertion site of the cranial cruciate ligament), two graft preloads (5 N and 20 N), and three flexion angles at the time of graft fixation (15°, 30° and 90°) were examined. The tibial insertion site and preload did not have as great an effect on graft force as did the flexion angle of the limb at time of graft fixation. Graft forces were highest when reconstructions were performed with the limb in 90° of flexion (ρ <0.0001). This study supports the notion that intracapsular grafts should be fixed with the limb in a normal standing angle.A five degree of freedom test apparatus was used to evaluate the effect of graft location, graft preload, and limb flexion angle at time of graft fixation on reconstructions of the cranial cruciate ligament deficient stifle. Our results suggest that intracapsular grafts should not be fixed with the limb in 90° of flexion, but in a normal standing angle.

Download Full-text

An in vitro Comparison of Two Replacement Techniques Utilizing Fascia Lata after Cranial Cruciate Ligament Transection in the Dog

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1633025 ◽

1993 ◽

Vol 06 (02) ◽

pp. 85-92 ◽

Cited By ~ 3

Author(s):

G. L. Coetzee

Keyword(s):

Femoral Condyle ◽

Cruciate Ligament ◽

Maximum Load ◽

Fascia Lata ◽

Patellar Ligament ◽

Cross Sectional ◽

Cranial Cruciate Ligament ◽

Replacement Technique ◽

Over The Top

SummaryThe immediate postoperative biomechanical properties of an “underand-over” cranial cruciate ligament (CCL) replacement technique consisting of fascia lata and the lateral onethird of the patellar ligament, were compared with that of a modified intra- and extracapsular “under-and-over-the-top” (UOTT) method. The right CCL in twelve adult dogs was dissected out and replaced with an autograft. The contralateral, intact CCL served as the control. In group A, the graft was secured to the lateral femoral condyle with a spiked washer and screw. In group B the intracapsular graft was secured to the lateral femoro-fabellar ligament, and the remainder to the patellar tendon. Both CCL replacement techniques exhibited a 2.0 ± 0.5 mm anterior drawer immediately after the operation. After skeletonization of the stifles, the length and cross-sectional area of the intact CCL and CCL substitutes were determined. Each bone-ligament unit was tested in linear tension to failure at a fixed distraction rate of 15 mm/s with the stifle in 120° flexion. Data was processed to obtain the corresponding material parameters (modulus, stress and strain in the linear loading region, and energy absorption to maximum load).The immediate postoperative structural and material properties of the “under-and-over” cranial cruciate ligament replacement technique with autogenous fascia lata, were compared to that of a modified intra- and extracapsular “under-and-over-the-top” (UOTT) method. The combined UOT T technique was slightly stronger (6%), but allowed 2.8 ± 0.9 mm more cranial tibial displacement at maximum linear force.

Download Full-text

Biomechanical Properties of the Stifle Joint Lateral Collateral Ligament in Dogs

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1633103 ◽

1992 ◽

Vol 05 (04) ◽

pp. 158-162 ◽

Cited By ~ 1

Author(s):

D. Blackketter ◽

J Harari ◽

J. Dupuis

Keyword(s):

Mechanical Properties ◽

Cruciate Ligament ◽

Lateral Collateral Ligament ◽

Biomechanical Properties ◽

Fibular Head ◽

Joint Stability ◽

Collateral Ligament ◽

Cranial Cruciate Ligament ◽

Stifle Joint

Bone/lateral collateral ligament/bone preparations were tested and structural mechanical properties compared to properties of cranial cruciate ligament in 15 dogs. The lateral collateral ligament has sufficient stiffness to provide stifle joint stability and strength to resist acute overload following fibular head transposition.

Download Full-text

Evaluation of Positive Contrast Arthrography in Canine Cranial Cruciate Ligament Disease

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1632495 ◽

1996 ◽

Vol 09 (01) ◽

pp. 10-3 ◽

Cited By ~ 2

Author(s):

D.N. Aron ◽

R. Roberts ◽

J. Stallings ◽

J. Brown ◽

C.W. Hay

Keyword(s):

Articular Surface ◽

Cruciate Ligament ◽

Positive Contrast ◽

Joint Effusion ◽

Radiographic Evaluation ◽

Cranial Cruciate Ligament ◽

Joint Pathology ◽

Meniscal Pathology ◽

Cranial Cruciate Ligament Disease ◽

Better Than

SummaryArthrographic and intraoperative evaluations of stifles affected with cranial cruciate disease were compared. Arthrography did not appear to be helpful in predicting cranial cruciate ligament pathology. The caudal cruciate ligament was consistently not visualized in the arthrograms and was normal at surgery. The menisci were visualized consistently in the arthrograms, but conclusions could not be made as to the benefit of arthrography in predicting meniscal pathology. Arthrography was not helpful in predicting joint capsule and femoral articular surface pathology. Survey radiographic evaluation was better than arthrography in evaluating joint pathology. When cruciate injury is suspected, after history and physical examination, survey radiographs are better than positive contrast arthrograms at supporting the diagnosis.Positive contrast arthrography was evaluated as a diagnostic aid in canine cranial cruciate ligament disease. It did not appear to be useful in predicting joint pathology. With arthrography, both menisci could be visualized and evaluated for abnormalities. Joint effusion and presence of osteophytes evaluated on survey radiographs was better than arthrography in evaluating joint pathology.

Download Full-text

Effect of Suture Type on Stifle Joint Biomechanics After Extra-Articular Repair of Cranial Cruciate Ligament Transection in the Dog

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1633270 ◽

1991 ◽

Vol 4 (04) ◽

pp. 144-149 ◽

Cited By ~ 4

Author(s):

M. S. Bauer ◽

W. E. Blevins ◽

W. R. Widmer ◽

Jaqueline Davidson ◽

S. W. Aiken ◽

...

Keyword(s):

Cruciate Ligament ◽

Tibial Tuberosity ◽

Cranial Cruciate Ligament ◽

Stifle Joint ◽

Ligament Rupture ◽

Cruciate Ligament Rupture ◽

Before And After ◽

Joint Biomechanics ◽

Cranial Cruciate Ligament Rupture

SummaryThe effect of two suture types, monofilament polybutester and braided polyester, on stifle joint biomechanics after extra-articular repair of cranial cruciate ligament rupture was evaluated by analysis of the instant centre of motion. The instant centres of motion and resulting velocity vectors were determined radiographically on both stifles of eight fresh canine cadavers before and after cranial cruciate ligament transection. After ligament transection, all 16 stifles were repaired with an extra-articular technique utilizing a double strand of suture placed between the lateral fabella and the tibial tuberosity. One stifle on each cadaver was repaired with each suture type. The instant centres of motion and resulting velocity vectors were re-evaluated post repair. All stifles had normal instant centres of motion prior to transection of the cranial cruciate ligament. Neither ligament transection nor extra-articular repair with either suture type resulted in an abnormal change in the instant centre of motion.

Download Full-text