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      Genetic improvement of hip-extended scores in 3 breeds of guide dogs using estimated breeding values: Notable progress but more improvement is needed

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          Abstract

          Two hip quality phenotypes—a hip-extended score assigned by a board certified radiologist and the PennHIP distraction index—were analyzed to estimate genetic parameters and to calculate estimated breeding values used for selecting replacement breeders. Radiographs obtained at 12–18 months of age were available on 5,201 German Shepherd Dogs, 4,987 Labrador Retrievers and 2,308 Golden Retrievers. Obtained by fitting a two-trait model using Bayesian techniques, estimates of heritability for the hip-extended score were 0.76, 0.72, and 0.41 in German Shepherd Dogs, Labrador Retrievers, and Golden Retrievers, respectively, while estimated heritabilities for distraction index were 0.60, 0.66 and 0.59, respectively. Genetic correlations between the two hip quality measures were −0.28 in German Shepherd Dogs, −0.21 in Labrador Retrievers, and −0.29 in Golden Retrievers. Genetic selection for improved hip quality based upon the hip extended score phenotype began in 1980. Among first generation puppies, 34% of 273 German Shepherd Dogs, 55% of 323 Labrador Retrievers, and 43% of 51 Golden Retrievers had an Excellent hip extended score. After 8 generations of selection, mostly based on estimated breeding values derived from the hip extended score, over 93% of 695 German Shepherd Dogs, 94% of 528 Labrador Retrievers, and 87% of 116 Golden Retrievers received an Excellent hip extended score. With respect to PennHIP distraction index values among these same dogs, median values were at or above 0.30 for all 3 breeds meaning that half or more of dogs possessing the Excellent hip-extended-score phenotype remained susceptible to developing the osteoarthritis of canine hip dysplasia. Genetic improvement of the hip-extended-view phenotype to its desired biological endpoint left a surprising proportion of dogs expressing sufficient joint laxity to place them in an osteoarthritis at-risk state as they age. Only by directly applying selection pressure to reduce distraction index was marked reduction in joint laxity noted.

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          Computing the Diagonal Elements and Inverse of a Large Numerator Relationship Matrix

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            Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip joint in dogs.

            To evaluate the effects of diet restriction on development of radiographic evidence of hip joint osteoarthritis in dogs. Longitudinal cohort study. 48 Labrador Retrievers from 7 litters. Forty-eight 6-week-old puppies from 7 litters were paired with littermates by sex and weight, and each pairmate was randomly assigned to 1 of 2 groups of 24 dogs each. Starting at 8 weeks of age, 1 group was fed ad libitum (control fed) and the other was fed 25% less (restricted fed) of the same diet for life on a pairwise basis. The dogs' hip joints were radiographed in the standard ventrodorsal hip-extended view at multiple intervals prior to 1 year of age and at annual intervals thereafter on the basis of birth anniversary. A board-certified radiologist unaware of group assignment scored the radiographs for evidence of osteoarthritis. Prevalence of radiographic evidence of hip joint osteoarthritis in all dogs increased linearly throughout the study, from an overall prevalence of 15% at 2 years to 67% by 14 years. Restricted-fed dogs had lower prevalence and later onset of hip joint osteoarthritis. Median age at first identification of radiographic evidence of hip joint osteoarthritis was significantly lower in the control-fed group (6 years), compared with the restricted-fed group (12 years). Restricted feeding delayed or prevented development of radiographic signs of hip joint osteoarthritis in this cohort of Labrador Retrievers. Lifetime maintenance of 25% diet restriction delayed onset and reduced severity of hip joint osteoarthritis, thus favorably affecting both duration and quality of life. In addition, the data indicated that development of hip joint osteoarthritis was not bimodal in these dogs but occurred as a continuum throughout life.
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              Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in German Shepherd Dogs, Golden Retrievers, Labrador Retrievers, and Rottweilers.

              To determine whether age, breed, sex, weight, or distraction index (DI) was associated with the risk that dogs of 4 common breeds (German Shepherd Dog, Golden Retriever, Labrador Retriever, Rottweiler) would have radiographic evidence of degenerative joint disease (DJD) associated with hip dysplasia. Cross-sectional prevalence study. 15,742 dogs. Hips of dogs were evaluated radiographically by use of the ventrodorsal hip-extended view, the compression v ew, and the distraction view. The ventrodorsal hip-extended view was examined to determine whether dogs had DJD. For each breed, a multiple logistic regression model incorporating age, sex, weight, and DI was created. For each breed, disease-susceptibility curves were produced, using all dogs, regardless of age, and dogs grouped on the basis of age. Weight and DI were significant risk factors for DJD in all breeds. For German Shepherd Dogs, the risk of having DJD was 4.95 times the risk for dogs of the other 3 breeds combined. In all breeds, the probability of having DJD increased with age. Results indicated that the probability of having hip DJD increased with hip joint laxity as measured by use of DI. This association was breed-specific, indicating that breed-specific information on disease susceptibility should be incorporated when making breeding decisions and when deciding on possible surgical treatment of hip dysplasia.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Visualization
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 February 2019
                2019
                : 14
                : 2
                : e0212544
                Affiliations
                [1 ] The Seeing Eye, Inc, Morristown, New Jersey, United States of America
                [2 ] Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, United States of America
                University of Sydney Faculty of Veterinary Science, AUSTRALIA
                Author notes

                Competing Interests: Most of the data collection for this publication occurred while PennHIP was a not-for-profit service wholly owned and operated by the University of Pennsylvania. In December, 2013 PennHIP was acquired by Antech Imaging Services of Fountain Valley, CA, United States of America. Antech Imaging Services is a segment of VCAAntech, which was purchased in 2018 by Mars, Inc. Since 2013 PennHIP has been a for-profit diagnostic service available world-wide. Dr. Gail K. Smith is currently an employee of Antech Imaging Services, where he is the Director of AIS PennHIP. The Seeing Eye, Inc. is a not-for-profit charity with a focused mission to provide healthy, well-trained dogs to serve as guides for blind people. In pursuit of this mission, The Seeing Eye has, occasionally, funded targeted research in areas of canine health. One such project was to develop an improved, alternative method for assessing hip quality in young dogs. Funding for much of this targeted research support was channeled through Morris Animal Foundation, who provides oversight and an established peer-review process for awarding research grants. Some of the funds dispensed by Morris Animal Foundation for developing the distraction index method originated with The Seeing Eye, Inc. During some of the years when this funding support was provided by The Seeing Eye, Drs. Eldin A. Leighton and Dolores Holle were employed by The Seeing Eye and participated in the decision-making process that led to this funding support. After the PennHIP program was established as a service provided by the University of Pennsylvania and later by AIS, The Seeing Eye was a consumer of the service, obtaining PennHIP scores on thousands of dogs under contract with the University of Pennsylvania and later with AIS. The Seeing Eye holds no patents or income producing interest in PennHIP. Our disclosure of these relationships is intended to provide transparency to our readers. Furthermore, these relationships do not alter our adherence to PLOS ONE policies on sharing data and materials.

                [¤a]

                Current address: Canine Genetic Services, LLC, Great Falls, Virginia, United States of America

                [¤b]

                Current address: West Chester, Pennsylvania, United States of America

                [¤c]

                Current address: Veterinary Specialty Hospital of the Carolinas, Cary, North Carolina, United States of America

                [¤d]

                Current address: Department of Small Animal Medicine and Surgery, University of Georgia, Athens, Georgia, United States of America

                [¤e]

                Current address: Seattle Veterinary Specialists, Seattle, Washington, United States of America

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-3032-0315
                Article
                PONE-D-17-31523
                10.1371/journal.pone.0212544
                6386262
                30794614
                58e6f0ce-81d7-4ce7-b6d8-1ba489b63831
                © 2019 Leighton et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 August 2017
                : 5 February 2019
                Page count
                Figures: 12, Tables: 5, Pages: 33
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100001250, Morris Animal Foundation;
                Award Recipient :
                Drs. Gail K. Smith and Daryl N. Biery acknowledge generous financial support from The Seeing Eye, Inc., Morristown, NJ, for funds obtained from and administered by Morris Animal Foundation under grant 93CA-5. All authors acknowledge generous financial support received from the governor and commonwealth of the state of Pennsylvania.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Pelvis
                Hip
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Pelvis
                Hip
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Dogs
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Animal Types
                Pets and Companion Animals
                Biology and Life Sciences
                Zoology
                Animal Types
                Pets and Companion Animals
                Medicine and Health Sciences
                Clinical Genetics
                Genetic Diseases
                Autosomal Recessive Diseases
                Glycogen Storage Diseases
                Medicine and Health Sciences
                Metabolic Disorders
                Inherited Metabolic Disorders
                Glycogen Storage Diseases
                Biology and Life Sciences
                Genetics
                Phenotypes
                Biology and Life Sciences
                Genetics
                Heredity
                Medicine and Health Sciences
                Rheumatology
                Arthritis
                Osteoarthritis
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Skeletal Joints
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Skeletal Joints
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                All relevant data are available within the paper and its Supporting Information files.

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