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Peter C Thomson - One of the best experts on this subject based on the ideXlab platform.
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Estimated Breeding Values for Canine Hip Dysplasia Radiographic Traits in a Cohort of Australian German Shepherd
2016Co-Authors: Bethany J. Wilson, Frank W. Nicholas, John W. James, Claire M. Wade, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a serious and common musculoskeletal disease of pedigree dogs and therefore represents both an important welfare concern and an imperative breeding priority. The typical heritability estimates for radiographic CHD traits suggest that the accuracy of breeding dog selection could be substantially improved by the use of estimated breeding values (EBVs) in place of selection based on phenotypes of individuals. The British Veterinary Association/Kennel Club scoring method is a complex measure composed of nine bilateral ordinal traits, intended to evaluate both early and late dysplastic changes. However, the ordinal nature of the traits may represent a technical challenge for calculation of EBVs using linear methods. The purpose of the current study was to calculate EBVs of British Veterinary Association/Kennel Club traits in the Australian population of German Shepherd Dogs, using linear (both as individual traits and a summed phenotype), binary and ordinal methods to determine the optimal method for EBV calculation. Ordinal EBVs correlated well with linear EBVs (r = 0.90–0.99) and somewhat well with EBVs for the sum of the individual traits (r = 0.58–0.92). Correlation of ordinal and binary EBVs varied widely (r = 0.24–0.99) depending on the trait and cut-point considered. The ordinal EBVs have increased accuracy (0.48–0.69) of selection compared with accuracies from individual phenotype-based selection (0.40–0.52). Despite the high correlations between linear and ordinal EBVs, the underlying relationsHip between EBVs calculated by the two methods was not always linear, leading us to suggest that ordinal models should be used whereve
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genetic correlations among Canine Hip Dysplasia radiographic traits in a cohort of australian german shepherd dogs and implications for the design of a more effective genetic control program
PLOS ONE, 2013Co-Authors: Bethany Wilson, F W Nicholas, John W. James, Claire M. Wade, H W Raadsma, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a common musculoskeletal disease in pedigree dog populations. It can cause severe pain and dysfunction which may require extensive medication and/or surgical treatment and often ultimately requires humane euthanasia. CHD has been found to be moderately heritable and, given its impact on welfare, should be considered an imperative breeding priority. The British Veterinary Association/Kennel Club scoring method is one of several measures used to assess the genetic propensity of potential breeding stock for dysplastic changes to the Hips based on radiographic examination. It is a complex measure composed of nine ordinal traits, intended to evaluate both early and late dysplastic changes. It would be highly desirable if estimated breeding values (EBVs) for these nine traits were consolidated into a simpler, EBV-based, selection index more easily usable by breeders. A multivariate analysis on the phenotype scores from an Australian cohort of 13,124 German Shepherd Dogs (GSDs) returned genetic correlations between 0.48–0.97 for the nine traits which fell into two trait groups, Group 1 reflecting early changes (“laxity”) and Group 2 reflecting late changes (“osteoarthritis”). Principal components analysis of the ordinal EBVs suggested the same pattern, with strong differentiation between “laxity” and “osteoarthritis” traits in the second component. Taking account of all results, we recommend interim use of two selection indexes: the first being the average of ordinal EBVs for “laxity” traits and the second being the average of ordinal EBVs for “osteoarthritis” traits. The correlation between these two selection indexes (0.771–0.774) is sufficiently less than unity enabling the selection of dogs with different genetic propensity for laxity and for osteoarthritic CHD changes in GSDs; this may also be applicable in other breeds. Dogs with low propensity for severe osteoarthritic change in the presence of laxity may be of interest both in molecular research and breeding programs.
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estimated breeding values for Canine Hip Dysplasia radiographic traits in a cohort of australian german shepherd dogs
PLOS ONE, 2013Co-Authors: Bethany Wilson, F W Nicholas, John W. James, Claire M. Wade, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a serious and common musculoskeletal disease of pedigree dogs and therefore represents both an important welfare concern and an imperative breeding priority. The typical heritability estimates for radiographic CHD traits suggest that the accuracy of breeding dog selection could be substantially improved by the use of estimated breeding values (EBVs) in place of selection based on phenotypes of individuals. The British Veterinary Association/Kennel Club scoring method is a complex measure composed of nine bilateral ordinal traits, intended to evaluate both early and late dysplastic changes. However, the ordinal nature of the traits may represent a technical challenge for calculation of EBVs using linear methods. The purpose of the current study was to calculate EBVs of British Veterinary Association/Kennel Club traits in the Australian population of German Shepherd Dogs, using linear (both as individual traits and a summed phenotype), binary and ordinal methods to determine the optimal method for EBV calculation. Ordinal EBVs correlated well with linear EBVs (r = 0.90-0.99) and somewhat well with EBVs for the sum of the individual traits (r = 0.58-0.92). Correlation of ordinal and binary EBVs varied widely (r = 0.24-0.99) depending on the trait and cut-point considered. The ordinal EBVs have increased accuracy (0.48-0.69) of selection compared with accuracies from individual phenotype-based selection (0.40-0.52). Despite the high correlations between linear and ordinal EBVs, the underlying relationsHip between EBVs calculated by the two methods was not always linear, leading us to suggest that ordinal models should be used wherever possible. As the population of German Shepherd Dogs which was studied was purportedly under selection for the traits studied, we examined the EBVs for evidence of a genetic trend in these traits and found substantial genetic improvement over time. This study suggests the use of ordinal EBVs could increase the rate of genetic improvement in this population.
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heritability and phenotypic variation of Canine Hip Dysplasia radiographic traits in a cohort of australian german shepherd dogs
PLOS ONE, 2012Co-Authors: Bethany Wilson, F W Nicholas, John W. James, Claire M. Wade, Imke Tammen, H W Raadsma, Kao Castle, Peter C ThomsonAbstract: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.
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selection against Canine Hip Dysplasia success or failure
Veterinary Journal, 2011Co-Authors: Bethany Wilson, F W Nicholas, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a multifactorial skeletal disorder which is very common in pedigree dogs and represents a huge concern for Canine welfare. Control schemes based on selective breeding have been in operation for decades. The aim of these schemes is to reduce the impact of CHD on Canine welfare by selecting for reduced radiographic evidence of CHD pathology as assessed by a variety of phenotypes. There is less information regarding the genotypic correlation between these phenotypes and the impact of CHD on Canine welfare. Although the phenotypes chosen as the basis for these control schemes have displayed heritable phenotypic variation in many studies, success in achieving improvement in the phenotypes has been mixed. There is significant room for improvement in the current schemes through the use of estimated breeding values (EBVs), which can combine a dog's CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are proven to be genetically correlated with CHD (especially elbow Dysplasia phenotypes), and information from genetic tests for population-relevant DNA markers, as such tests become available. Additionally, breed clubs should be encouraged and assisted to formulate rational, evidenced-based breeding recommendations for CHD which suit their individual circumstances and dynamically to adjust the breeding recommendations based on continuous tracking of CHD genetic trends. These improvements can assist in safely and effectively reducing the impact of CHD on pedigree dog welfare.
Ottmar Distl - One of the best experts on this subject based on the ideXlab platform.
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Multiple loci associated with Canine Hip Dysplasia (CHD) in German shepherd dogs
Mammalian Genome, 2014Co-Authors: Lena Fels, Yvonne Marschall, Ute Philipp, Ottmar DistlAbstract:Canine Hip Dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we developed 37 informative single nucleotide polymorphisms (SNPs) within 13 quantitative trait loci (QTL) previously identified for German shepherd dogs. These SNPs were genotyped in 95 German shepherd dogs affected by CHD and 95 breed, sex, and birth year-matched controls. A total of ten SNPs significant at a nominal P value of 0.05 were validated in 843 German shepherd dogs including 277 unaffected dogs and 566 CHD-affected dogs. Cases and controls were sampled from the whole German shepherd dog population in Germany in such a way that mean coancestry coefficients were below 0.1 % within cases and controls as well as among cases and controls. We identified nine SNPs significantly associated with CHD within five QTL on dog chromosomes (CFA) 3, 9, 26, 33, and 34. Genotype effects of these nine SNPs explained between 22 and 34 % of the phenotypic variance of Hip Dysplasia in German shepherd dogs. The strongest associated SNPs were located on CFA33 and 34 within the candidate genes PNCP , TRIO , and SLC6A3 . Thus, the present study validated positional candidate genes within five QTL for CHD.
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identification and validation of quantitative trait loci qtl for Canine Hip Dysplasia chd in german shepherd dogs
PLOS ONE, 2014Co-Authors: Lena Fels, Ottmar DistlAbstract:Canine Hip Dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix Canine high density SNP cHip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA) 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were <0.1%. Genotype effects of these SNPs explained 20–32% of the phenotypic variance of CHD in German Shepherd Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL) and a novel QTL for CHD in German Shepherd Dogs.
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Identification of quantitative trait loci (QTL) for Canine Hip Dysplasia and Canine elbow Dysplasia in Bernese mountain dogs.
PloS one, 2012Co-Authors: Sophia Pfahler, Ottmar DistlAbstract:A genome-wide association study for Canine Hip Dysplasia (CHD) and Canine elbow Dysplasia (CED) using the Illumina Canine high density bead cHip had been performed for 174 Bernese mountain dogs. General and mixed linear model analysis identified two different regions with single nucleotide polymorphisms (SNPs) on dog chromosome (CFA) 14 significantly associated with CHD and a further significantly CHD-associated region on CFA37. For CED, four SNPs on CFA11 and 27 were significantly associated. The identified SNPs of four associated regions included nearby candidate genes. These possible positional candidates were the genes PON2 on CFA14 and FN1 on CFA37 for CHD and the genes LMNB1 on CFA11 and WNT10B on CFA27 for CED.
Pamela Wiener - One of the best experts on this subject based on the ideXlab platform.
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genome wide association studies for Canine Hip Dysplasia in single and multiple populations implications and potential novel risk loci
BMC Genomics, 2021Co-Authors: S Wang, Dylan N Clements, Pamela Wiener, E. Strandberg, Per Arvelius, Juliane FriedrichAbstract:Association mapping studies of quantitative trait loci (QTL) for Canine Hip Dysplasia (CHD) can contribute to the understanding of the genetic background of this common and debilitating disease and might contribute to its genetic improvement. The power of association studies for CHD is limited by relatively small sample numbers for CHD records within countries, suggesting potential benefits of joining data across countries. However, this is complicated due to the use of different scoring systems across countries. In this study, we incorporated routinely assessed CHD records and genotype data of German Shepherd dogs from two countries (UK and Sweden) to perform genome-wide association studies (GWAS) within populations using different variations of CHD phenotypes. As phenotypes, dogs were either classified into cases and controls based on the Federation Cynologique Internationale (FCI) five-level grading of the worst Hip or the FCI grade was treated as an ordinal trait. In a subsequent meta-analysis, we added publicly available data from a Finnish population and performed the GWAS across all populations. Genetic associations for the CHD phenotypes were evaluated in a linear mixed model using 62,089 SNPs. Multiple SNPs with genome-wide significant and suggestive associations were detected in single-population GWAS and the meta-analysis. Few of these SNPs overlapped between populations or between single-population GWAS and the meta-analysis, suggesting that many CHD-related QTL are population-specific. More significant or suggestive SNPs were identified when FCI grades were used as phenotypes in comparison to the case-control approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional candidate genes associated with Hip Dysplasia. Our findings confirm the complex genetic nature of Hip Dysplasia in dogs, with multiple loci associated with the trait, most of which are population-specific. Routinely assessed CHD information collected across countries provide an opportunity to increase sample sizes and statistical power for association studies. While the lack of standardisation of CHD assessment schemes across countries poses a challenge, we showed that conversion of traits can be utilised to overcome this obstacle.
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methods to improve joint genetic evaluation of Canine Hip Dysplasia across bva kc and fci screening schemes
Frontiers in Veterinary Science, 2020Co-Authors: S Wang, E. Strandberg, Juliane Friedrich, Per Arvelius, Pamela WienerAbstract:The BVA/KC (British Veterinary Association/Kennel Club) and FCI (Federation Cynologique Internationale) are the main screening schemes used to evaluate the status of Canine Hip Dysplasia (HD) in Europe. Jointly utilizing HD records from both BVA/KC and FCI schemes could improve the reliability of genetic evaluation within and across countries. In this study, HD scores for German shepherd dogs (GSDs) in the UK (using the BVA/KC scheme) and Sweden (using the FCI scheme) were used to investigate how to better operate joint genetic evaluations across the two schemes. It was shown that under a bivariate model, which regarded BVA/KC and FCI scores as different traits, the estimated genetic correlations between the UK and Swedish GSD populations were the same when using BVA/KC total or worse Hip scores and for single-country or joint analysis of both the UK and Swedish populations. Under a univariate model that converted BVA/KC scores into FCI scores, the predictability of estimated breeding values was slightly improved by performing a joint analysis.
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joint genomic prediction of Canine Hip Dysplasia in uk and us labrador retrievers
Frontiers in Genetics, 2018Co-Authors: Stefan M Edwards, John Woolliams, John M Hickey, Sarah C Blott, Dylan N Clements, Enrique Sanchezmolano, Rory J Todhunter, Pamela WienerAbstract:Canine Hip Dysplasia, a debilitating orthopedic disorder that leads to osteoarthritis and cartilage degeneration, is common in several large-sized dog breeds and shows moderate heritability suggesting that selection can reduce prevalence. Estimating genomic breeding values require large reference populations, which are expensive to genotype for development of genomic prediction tools. Combining datasets from different countries could be an option to help build larger reference datasets without incurring extra genotyping costs. Our objective was to evaluate genomic prediction based on a combination of UK and US datasets of genotyped dogs with records of Norberg angle scores, related to Canine Hip Dysplasia. Prediction accuracies using a single population were 0.179 and 0.290 for 1179 and 242 UK and US Labrador Retrievers, respectively. Prediction accuracies changed to 0.189 and 0.260, with an increased bias of genomic breeding values when using a joint training set (biased upwards for the US population and downwards for the UK population). Our results show that in this study of Canine Hip Dysplasia, little or no benefit was gained from using a joint training set, as compared to using a single population as training set. We attribute this to differences in the genetic background of the two populations, as well as the small sample size of the US dataset.
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2018Co-Authors: Stefan M Edwards, John Woolliams, John M Hickey, Sarah C Blott, Dylan N Clements, Rory J Todhunter, Enrique Sánchez-molano, Pamela WienerAbstract:Canine Hip Dysplasia, a debilitating orthopedic disorder that leads to osteoarthritis and cartilage degeneration, is common in several large-sized dog breeds and shows moderate heritability suggesting that selection can reduce prevalence. Estimating genomic breeding values require large reference populations, which are expensive to genotype for development of genomic prediction tools. Combining datasets from different countries could be an option to help build larger reference datasets without incurring extra genotyping costs. Our objective was to evaluate genomic prediction based on a combination of UK and US datasets of genotyped dogs with records of Norberg angle scores, related to Canine Hip Dysplasia. Prediction accuracies using a single population were 0.179 and 0.290 for 1,179 and 242 UK and US Labrador Retrievers, respectively. Prediction accuracies changed to 0.189 and 0.260, with an increased bias of genomic breeding values when using a joint training set (biased upwards for the US population and downwards for the UK population). Our results show that in this study of Canine Hip Dysplasia, little or no benefit was gained from using a joint training set as compared to using a single population as training set. We attribute this to differences in the genetic background of the two populations as well as the small sample size of the US dataset.
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genomic prediction of traits related to Canine Hip Dysplasia
Frontiers in Genetics, 2015Co-Authors: Enrique Sanchezmolano, Sarah C Blott, Dylan N Clements, Pamela Wiener, Ricardo Pongwong, John WoolliamsAbstract:Increased concern for the welfare of pedigree dogs has led to development of selection programs against inherited diseases. An example is Canine Hip Dysplasia (CHD), which has a moderate heritability and a high prevalence in some large-sized breeds. To date, selection using phenotypes has led to only modest improvement, and alternative strategies such as genomic selection (GS) may prove more effective. The primary aims of this study were to compare the performance of pedigree- and genomic-based breeding against CHD in the UK Labrador retriever population and to evaluate the performance of different GS methods. A sample of 1179 Labrador Retrievers evaluated for CHD according to the UK scoring method (Hip score, HS) was genotyped with the Illumina CanineHD BeadCHip. Twelve functions of HS and its component traits were analyzed using different statistical methods (GBLUP, Bayes C and Single-Step methods), and results were compared with a pedigree-based approach (BLUP) using cross-validation. Genomic methods resulted in similar or higher accuracies than pedigree-based methods with training sets of 944 individuals for all but the untransformed HS, suggesting that GS is an effective strategy. GBLUP and Bayes C gave similar prediction accuracies for HS and related traits, indicating a polygenic architecture. This conclusion was also supported by the low accuracies obtained in additional GBLUP analyses performed using only the SNPs with highest test statistics, also indicating that marker-assisted selection (MAS) would not be as effective as GS. A Single-Step method that combines genomic and pedigree information also showed higher accuracy than GBLUP and Bayes C for the log-transformed HS, which is currently used for pedigree based evaluations in UK. In conclusion, GS is a promising alternative to pedigree-based selection against CHD, requiring more phenotypes with genomic data to improve further the accuracy of prediction.
Bethany Wilson - One of the best experts on this subject based on the ideXlab platform.
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Canine Hip Dysplasia towards more effective selection
New Zealand Veterinary Journal, 2015Co-Authors: Bethany Wilson, F W NicholasAbstract:This issue of the New Zealand Veterinary Journal includes two important and timely papers on selection against Canine Hip Dysplasia (CHD) in New Zealand. The first, a review article by Soo and Wort...
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genetic correlations among Canine Hip Dysplasia radiographic traits in a cohort of australian german shepherd dogs and implications for the design of a more effective genetic control program
PLOS ONE, 2013Co-Authors: Bethany Wilson, F W Nicholas, John W. James, Claire M. Wade, H W Raadsma, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a common musculoskeletal disease in pedigree dog populations. It can cause severe pain and dysfunction which may require extensive medication and/or surgical treatment and often ultimately requires humane euthanasia. CHD has been found to be moderately heritable and, given its impact on welfare, should be considered an imperative breeding priority. The British Veterinary Association/Kennel Club scoring method is one of several measures used to assess the genetic propensity of potential breeding stock for dysplastic changes to the Hips based on radiographic examination. It is a complex measure composed of nine ordinal traits, intended to evaluate both early and late dysplastic changes. It would be highly desirable if estimated breeding values (EBVs) for these nine traits were consolidated into a simpler, EBV-based, selection index more easily usable by breeders. A multivariate analysis on the phenotype scores from an Australian cohort of 13,124 German Shepherd Dogs (GSDs) returned genetic correlations between 0.48–0.97 for the nine traits which fell into two trait groups, Group 1 reflecting early changes (“laxity”) and Group 2 reflecting late changes (“osteoarthritis”). Principal components analysis of the ordinal EBVs suggested the same pattern, with strong differentiation between “laxity” and “osteoarthritis” traits in the second component. Taking account of all results, we recommend interim use of two selection indexes: the first being the average of ordinal EBVs for “laxity” traits and the second being the average of ordinal EBVs for “osteoarthritis” traits. The correlation between these two selection indexes (0.771–0.774) is sufficiently less than unity enabling the selection of dogs with different genetic propensity for laxity and for osteoarthritic CHD changes in GSDs; this may also be applicable in other breeds. Dogs with low propensity for severe osteoarthritic change in the presence of laxity may be of interest both in molecular research and breeding programs.
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estimated breeding values for Canine Hip Dysplasia radiographic traits in a cohort of australian german shepherd dogs
PLOS ONE, 2013Co-Authors: Bethany Wilson, F W Nicholas, John W. James, Claire M. Wade, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a serious and common musculoskeletal disease of pedigree dogs and therefore represents both an important welfare concern and an imperative breeding priority. The typical heritability estimates for radiographic CHD traits suggest that the accuracy of breeding dog selection could be substantially improved by the use of estimated breeding values (EBVs) in place of selection based on phenotypes of individuals. The British Veterinary Association/Kennel Club scoring method is a complex measure composed of nine bilateral ordinal traits, intended to evaluate both early and late dysplastic changes. However, the ordinal nature of the traits may represent a technical challenge for calculation of EBVs using linear methods. The purpose of the current study was to calculate EBVs of British Veterinary Association/Kennel Club traits in the Australian population of German Shepherd Dogs, using linear (both as individual traits and a summed phenotype), binary and ordinal methods to determine the optimal method for EBV calculation. Ordinal EBVs correlated well with linear EBVs (r = 0.90-0.99) and somewhat well with EBVs for the sum of the individual traits (r = 0.58-0.92). Correlation of ordinal and binary EBVs varied widely (r = 0.24-0.99) depending on the trait and cut-point considered. The ordinal EBVs have increased accuracy (0.48-0.69) of selection compared with accuracies from individual phenotype-based selection (0.40-0.52). Despite the high correlations between linear and ordinal EBVs, the underlying relationsHip between EBVs calculated by the two methods was not always linear, leading us to suggest that ordinal models should be used wherever possible. As the population of German Shepherd Dogs which was studied was purportedly under selection for the traits studied, we examined the EBVs for evidence of a genetic trend in these traits and found substantial genetic improvement over time. This study suggests the use of ordinal EBVs could increase the rate of genetic improvement in this population.
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heritability and phenotypic variation of Canine Hip Dysplasia radiographic traits in a cohort of australian german shepherd dogs
PLOS ONE, 2012Co-Authors: Bethany Wilson, F W Nicholas, John W. James, Claire M. Wade, Imke Tammen, H W Raadsma, Kao Castle, Peter C ThomsonAbstract: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.
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selection against Canine Hip Dysplasia success or failure
Veterinary Journal, 2011Co-Authors: Bethany Wilson, F W Nicholas, Peter C ThomsonAbstract:Canine Hip Dysplasia (CHD) is a multifactorial skeletal disorder which is very common in pedigree dogs and represents a huge concern for Canine welfare. Control schemes based on selective breeding have been in operation for decades. The aim of these schemes is to reduce the impact of CHD on Canine welfare by selecting for reduced radiographic evidence of CHD pathology as assessed by a variety of phenotypes. There is less information regarding the genotypic correlation between these phenotypes and the impact of CHD on Canine welfare. Although the phenotypes chosen as the basis for these control schemes have displayed heritable phenotypic variation in many studies, success in achieving improvement in the phenotypes has been mixed. There is significant room for improvement in the current schemes through the use of estimated breeding values (EBVs), which can combine a dog's CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are proven to be genetically correlated with CHD (especially elbow Dysplasia phenotypes), and information from genetic tests for population-relevant DNA markers, as such tests become available. Additionally, breed clubs should be encouraged and assisted to formulate rational, evidenced-based breeding recommendations for CHD which suit their individual circumstances and dynamically to adjust the breeding recommendations based on continuous tracking of CHD genetic trends. These improvements can assist in safely and effectively reducing the impact of CHD on pedigree dog welfare.
Antti Iivanainen - One of the best experts on this subject based on the ideXlab platform.
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an across breed validation study of 46 genetic markers in Canine Hip Dysplasia
BMC Genomics, 2021Co-Authors: Lea Mikkola, Anu K Lappalainen, Marjo K Hytonen, Hannes Lohi, Kaisa Kyostila, Jonas Donner, Antti IivanainenAbstract:Canine Hip Dysplasia (CHD) is a common disease, with a complex genetic background. Dogs with severe CHD sometimes also suffer from osteoarthritis (OA), an inflammatory, often painful and incurable condition. Previous studies have reported breed-specific genetic loci associated with different Hip Dysplasia and OA phenotypes. However, the independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sample sizes and the existence of population specific variants. We execute a validation study of 46 genetic markers in a cohort of nearly 1600 dogs from ten different breeds. We categorize the dogs into cases and controls according to the Hip scoring system defined by the Federation Cynologique Internationale (FCI). We validate 21 different loci associated on fourteen chromosomes. Twenty of these associated with CHD in specific breeds, whereas one locus is unique to the across-breed study. We show that genes involved in the neddylation pathway are enriched among the genes in the validated loci. Neddylation contributes to many cellular functions including inflammation. Our study successfully replicates many loci and highlights the complex genetic architecture of CHD. Further characterisation of the associated loci could reveal CHD-relevant genes and pathways for improved understanding of the disease pathogenesis.
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genetic dissection of Canine Hip Dysplasia phenotypes and osteoarthritis reveals three novel loci
BMC Genomics, 2019Co-Authors: Lea Mikkola, Saila Holopainen, Tiina Pessamorikawa, Anu K Lappalainen, Marjo K Hytonen, Hannes Lohi, Antti IivanainenAbstract:Hip Dysplasia and osteoarthritis continue to be prevalent problems in veterinary and human medicine. Canine Hip Dysplasia is particularly problematic as it massively affects several large-sized breeds and can cause a severe impairment of the quality of life. In Finland, the complex condition is categorized to five classes from normal to severe Dysplasia, but the categorization includes several sub-traits: congruity of the joint, Norberg angle, subluxation degree of the joint, shape and depth of the acetabulum, and osteoarthritis. Hip Dysplasia and osteoarthritis have been proposed to have separate genetic etiologies. Using Federation Cynologique Internationale -standardized ventrodorsal radiographs, German shepherds were rigorously phenotyped for osteoarthritis, and for joint incongruity by Norberg angle and femoral head center position in relation to dorsal acetabular edge. The affected dogs were categorized into mild, moderate and severe dysplastic phenotypes using official Hip scores. Three different genome-wide significant loci were uncovered. The strongest candidate genes for Hip joint incongruity were noggin (NOG), a bone and joint developmental gene on chromosome 9, and nanos C2HC-type zinc finger 1 (NANOS1), a regulator of matrix metalloproteinase 14 (MMP14) on chromosome 28. Osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for NADPH oxidase 3 (NOX3), an intriguing candidate for articular cartilage degradation, and AT-rich interactive domain 1B (ARID1B) that has been previously linked to joint laxity. Our findings highlight the complexity of Canine Hip Dysplasia phenotypes. In particular, the results of this study point to the potential involvement of specific and partially distinct loci and genes or pathways in the development of incongruity, mild Dysplasia, moderate-to-severe Dysplasia and osteoarthritis of Canine Hip joints. Further studies should unravel the unique and common mechanisms for the various sub-traits.
