Genomic analyses of withers height and linear conformation traits in German Warmblood horses using imputed sequence-level genotypes.

BACKGROUND: Body conformation, including withers height, is a major selection criterion in horse breeding and is associated with other important traits, such as health and performance. However, little is known about the genomic background of equine conformation. Therefore, the aim of this study was to use imputed sequence-level genotypes from up to 4891 German Warmblood horses to identify genomic regions associated with withers height and linear conformation traits. Furthermore, the traits were genetically characterised and putative causal variants for withers height were detected. RESULTS: A genome-wide association study (GWAS) for withers height confirmed the presence of a previously known quantitative trait locus (QTL) on Equus caballus (ECA) chromosome 3 close to the LCORL/NCAPG locus, which explained 16% of the phenotypic variance for withers height. An additional significant association signal was detected on ECA1. Further investigations of the region on ECA3 identified a few promising candidate causal variants for withers height, including a nonsense mutation in the coding sequence of the LCORL gene. The estimated heritability for withers height was 0.53 and ranged from 0 to 0.34 for the conformation traits. GWAS identified significantly associated variants for more than half of the investigated conformation traits, among which 13 showed a peak on ECA3 in the same region as withers height. Genetic parameter estimation revealed high genetic correlations between these traits and withers height for the QTL on ECA3. CONCLUSIONS: The use of imputed sequence-level genotypes from a large study cohort led to the discovery of novel QTL associated with conformation traits in German Warmblood horses. The results indicate the high relevance of the QTL on ECA3 for various conformation traits, including withers height, and contribute to deciphering causal mutations for body size in horses.

Phenotypic and genetic relationships between age at first calving, its component traits, and survival of heifers up to second calving.

The aim of this study was to answer the question whether models for genetic evaluations of longevity should include a correction for age at first calving (AFC). For this purpose, phenotypic and genetic relationships between AFC, its component traits age at first insemination (AFI) and interval from first to last insemination (FLI), and survival of different periods of the first lactation (S1: 0 to 49 d, S2: 50 to 249 d, S3: 250 d to second calving) were investigated. Data of 721,919 German Holstein heifers, being inseminated for the first time during the years from 2003 to 2012, were used for the analyses. Phenotypic correlations of AFI, FLI, and AFC to S1 to S3 were negative. Mean estimated heritabilities were 0.239 (AFI), 0.007 (FLI), and 0.103 (AFC) and 0.023 (S1), 0.016 (S2), and 0.028 (S3) on the observed scale. The genetic correlation between AFI and FLI was close to zero. Genetic correlations between AFI and the survival traits were -0.08 (S1), -0.02 (S2), and -0.10 (S3); those between FLI and the survival traits were -0.14 (S1), -0.20 (S2), and -0.44 (S3); and those between AFC and the survival traits were -0.09 (S1), -0.06 (S2), and -0.20 (S3). Some of these genetic correlations were different from zero, which suggests that correcting for AFC in genetic evaluations for longevity in dairy cows might remove functional genetic variance and should be reconsidered.

The genetic structure of longevity in dairy cows.

Longevity of dairy cows is determined by culling. Previous studies have shown that culling of dairy cows is not an unambiguous trait but rather the result of several reasons including diseases and selection decisions. The relative importance of these reasons is not stable over time, implying that genetic background of culling may vary over lifetime. Data of 7.6 million German Holstein cows were used to assess the detailed genetic correlation structure among 18 survival traits defined for the first 3 parities. Differences of genetic factors which determine survival of different production periods were found, showing a pattern with 3 genetically distinct periods within each parity: early lactation (calving until d 59), mid lactation (d 60 to 299), and late lactation (d 300 until next calving). Survival in first and later parities were found to be slightly genetically different from each other. The identified patterns were in good accordance with distributions of reasons for disposal, and correlations of estimated breeding values of survival traits for different periods to production and functional traits were generally plausible compared with literature regarding effects on the risk of culling. The study shows that genetic background of survival is variable not only across but also within parities. The results of the study can help developing more accurate models for routine genetic evaluations of longevity that account for nonunity genetic correlations between survival of different periods.

Leveraging Accelerometer Data for Lameness Detection in Dairy Cows: A Longitudinal Study of Six Farms in Germany.

Lameness in dairy cows poses a significant challenge to improving animal well-being and optimizing economic efficiency in the dairy industry. To address this, employing automated animal surveillance for early lameness detection and prevention through activity sensors proves to be a promising strategy. In this study, we analyzed activity (accelerometer) data and additional cow-individual and farm-related data from a longitudinal study involving 4860 Holstein dairy cows on six farms in Germany during 2015-2016. We designed and investigated various statistical models and chose a logistic regression model with mixed effects capable of detecting lameness with a sensitivity of 77%. Our results demonstrate the potential of automated animal surveillance and hold the promise of significantly improving lameness detection approaches in dairy livestock.

Quantifying the effect of Warmblood Fragile Foal Syndrome on foaling rates in the German riding horse population.

Awareness of breeders of Warmblood Fragile Foal Syndrome (WFFS) increased after a widely discussed case in the USA in 2018. The hereditary connective tissue disorder, first described by a US research group in 2011 and for which a commercial genetic test exists since 2013, is caused by a point mutation in the PLOD1 gene, inherited autosomal recessively. Extension of molecular genetic testing and reporting of test results of organized horse breeders to their studbooks implies new opportunities for analyses. In Germany, data are centrally accessible through the integrated equine data base allowing comprehensive and population-wide investigation of the role of WFFS. The objective of this study was statistical testing for associations between WFFS and reproductive performance of German riding horses and quantifying possible differences between WFFS carriers and non-carriers, also in respect of performance traits. For this purpose, covering data from 2008 to 2020 were provided by ten German studbooks, so almost 400,000 coverings and resulting foaling rates were available for multiple analyses of variance with general and mixed linear models using procedures GLM, MIXED and HPMIXED of SAS software (version 9.2). Published breeding values of stallions were used for respective comparisons of riding horse performance. Assuming a WFFS carrier frequency of 9.5-15.0% in Warmblood horses, Hardy Weinberg principle implied an expected difference of 2.4-3.7% in the foaling rates of carrier and non-carrier stallions. Our results provided statistical evidence of detrimental effects of WFFS on the reproductive performance of Warmblood horses with about 2.7% lower average foaling rate in carriers of the mutant allele than in WFFS free sires, if mated to an average mare population. Indications of favorable dressage performance of WFFS carriers were found. Reported WFFS cases indicate only the tip of the iceberg and assessing the impact of WFFS on reproduction requires consideration of premature foal losses.

Replacement of microsatellite markers by imputed medium-density SNP arrays for parentage control in German warmblood horses.

In horses, parentage control is currently performed based on an internationally standardized panel of 17 microsatellite (MS) markers comprising 12 mandatory and five optional markers. Unlike MS, single nucleotide polymorphism (SNP) profiles support a wider portfolio of genomic applications, including parentage control. A transition to SNP-based parentage control is favorable, but requires additional efforts for ensuring generation-overlapping availability of marker genotypes of the same type. To avoid double genotyping of either parents or offspring for changing to SNP technology and enable efficient transition, we tested whether MS genotypes used for parentage control could be reliably imputed from a medium-density SNP panel in German warmblood horses. Imputation accuracy was tested in a tenfold cross-validation with two approaches: within breed (option A) and across breeds (option B). Average imputation accuracies of 97.98% (A) and 96.17% (B) were achieved, respectively. Due to interbreed differences in genotyping rates, five MS markers of low genotyping rate (GTR; < 90%) could be imputed with higher accuracy within breed (98.18%) than across breeds (90.73%). MS markers with high GTR performed homogeneously well in option B (98.44%) and showed slightly lower accuracy in option A (97.90%). Among these markers, AHT5 proved to be problematic for imputation regardless of the approach, revealing accuracies of 86.40% (A) and 88.70% (B). Better results for MS markers with high GTR and savings in computational processing justified the choice of option B for routine implementation. To date, more than 9500 horses have undergone the new parentage control based on imputed MS genotypes.

Genetic and genomic characterization followed by single-step genomic evaluation of withers height in German Warmblood horses.

Reliability of genomic predictions is influenced by the size and genetic composition of the reference population. For German Warmblood horses, compilation of a reference population has been enabled through the cooperation of five German breeding associations. In this study, preliminary data from this joint reference population were used to genetically and genomically characterize withers height and to apply single-step methodology for estimating genomic breeding values for withers height. Using data on 2113 mares and their genomic information considering about 62,000 single nucleotide polymorphisms (SNPs), analysis of the genomic relationship revealed substructures reflecting breed origin and different breeding goals of the contributing breeding associations. A genome-wide association study confirmed a known quantitative trait locus (QTL) for withers height on equine chromosome (ECA) 3 close to LCORL and identified a further significant peak on ECA 1. Using a single-step approach with a combined relationship matrix, the estimated heritability for withers height was 0.31 (SE = 0.08) and the corresponding genomic breeding values ranged from - 2.94 to 2.96 cm. A mean reliability of 0.38 was realized for these breeding values. The analyses of withers height showed that compiling a reference population across breeds is a suitable strategy for German Warmblood horses. The single-step method is an appealing approach for practical genomic prediction in horses, because not many genotypes are available yet and animals without genotypes can by this way directly contribute to the estimation system.

A retrospective study on the prevalence of primary cataracts in two pedigrees from the German population of English Cocker Spaniels.

OBJECTIVE: Two pedigrees from the German English Cocker Spaniel population are presented to illustrate the familial occurrence of primary cataract (CAT) in single- and multicolored English Cocker Spaniels. The aim was to characterize similarities and differences in the prevalence and formation of CAT in these separately bred color variants of English Cocker Spaniels. MATERIALS: The study was based on the veterinary records for presumed inherited eye diseases of 1232 English Cocker Spaniels which were provided by the German panel of the European Eye Scheme for diagnosis of inherited eye diseases in animals (DOK, ). Data included information on 615 single-colored and 617 multicolored English Cocker Spaniels. RESULTS: CAT was diagnosed in 92 (14.96%) of the single-colored and 34 (5.51%) of the multicolored English Cocker Spaniels. The pedigree of the single-colored English Cocker Spaniels included 40 ophthalmologically examined dogs with 18 unaffected and 22 affected dogs. The pedigree of the multicolored English Cocker Spaniels contained 16 ophthalmologically examined dogs with 11 unaffected and five affected dogs. CONCLUSIONS: In both color variants of the English Cocker Spaniels different forms of primary CAT with respect to location within the lens occurred among close relatives. Appearance of CAT was very heterogeneous without obvious sex differences. The sample pedigrees do not support the assumption of familial segregation of specific forms of primary CAT in English Cocker Spaniels.

Bayesian estimation of genetic parameters for multivariate threshold and continuous phenotypes and molecular genetic data in simulated horse populations using Gibbs sampling.

BACKGROUND: Requirements for successful implementation of multivariate animal threshold models including phenotypic and genotypic information are not known yet. Here simulated horse data were used to investigate the properties of multivariate estimators of genetic parameters for categorical, continuous and molecular genetic data in the context of important radiological health traits using mixed linear-threshold animal models via Gibbs sampling. The simulated pedigree comprised 7 generations and 40000 animals per generation. Additive genetic values, residuals and fixed effects for one continuous trait and liabilities of four binary traits were simulated, resembling situations encountered in the Warmblood horse. Quantitative trait locus (QTL) effects and genetic marker information were simulated for one of the liabilities. Different scenarios with respect to recombination rate between genetic markers and QTL and polymorphism information content of genetic markers were studied. For each scenario ten replicates were sampled from the simulated population, and within each replicate six different datasets differing in number and distribution of animals with trait records and availability of genetic marker information were generated. (Co)Variance components were estimated using a Bayesian mixed linear-threshold animal model via Gibbs sampling. Residual variances were fixed to zero and a proper prior was used for the genetic covariance matrix. RESULTS: Effective sample sizes (ESS) and biases of genetic parameters differed significantly between datasets. Bias of heritability estimates was -6% to +6% for the continuous trait, -6% to +10% for the binary traits of moderate heritability, and -21% to +25% for the binary traits of low heritability. Additive genetic correlations were mostly underestimated between the continuous trait and binary traits of low heritability, under- or overestimated between the continuous trait and binary traits of moderate heritability, and overestimated between two binary traits. Use of trait information on two subsequent generations of animals increased ESS and reduced bias of parameter estimates more than mere increase of the number of informative animals from one generation. Consideration of genotype information as a fixed effect in the model resulted in overestimation of polygenic heritability of the QTL trait, but increased accuracy of estimated additive genetic correlations of the QTL trait. CONCLUSION: Combined use of phenotype and genotype information on parents and offspring will help to identify agonistic and antagonistic genetic correlations between traits of interests, facilitating design of effective multiple trait selection schemes.

Factors associated with the prevalence of osseous fragments in the limb joints of Hanoverian Warmblood horses.

Factors associated with the prevalence of osseous fragments (OF) in fetlock and hock joints were investigated in a population of young Hanoverian Warmblood horses selected for sale at auction from 1991 to 1998. The study was based on results of a standardized radiological examination of 3127 horses. The prevalences of OF in the two joints were significantly dependent on the date, type and quality of the auction, the region of origin and on the anticipated suitability of the horses for dressage and/or show-jumping. The probability of finding OF increased with wither-height. Furthermore, there was a significant association of the individual sire with the prevalence of OF in both fetlock and hock joints, and of the maternal grandsire with the prevalence of OF in the hock joints. Consequently, both non-genetic and genetic parameters should be taken into account in order to reduce the prevalence of OF in young Warmblood riding horses.

Genetic analyses of the radiographic appearance of the distal sesamoid bones in Hanoverian Warmblood horses.

OBJECTIVE: To evaluate whether additive genetic correlations existed between certain aspects of the radiographic appearance of the distal sesamoid (navicular) bones (RNB) or between RNB and other types of radiographic changes in the limbs of Hanoverian Warmblood horses. ANIMALS: 5,157 horses. PROCEDURES: Quasi-linear and binary traits were defined by the appearance of canales sesamoidales (CSs) and the structure and contour of the forelimb navicular bones (NBs). Prevalences of osseous fragments in the metacarphophalangeal and metatarsophalangeal (fetlock) and tarsocrural joints and deforming arthropathy in tarsal joints were analyzed as binary traits. Genetic parameters were estimated by use of multivariate linear models. RESULTS: Heritability estimates for the RNB traits ranged from 0.10 to 0.34. Additive genetic correlations among those traits were usually close to unity. Extensive radiographic changes in the NBs, including changes in CSs and alterations in structure and contour, had correlations with less distinct radiographic changes. Negative additive genetic correlations were observed between small numbers of short and conical CSs in the central portion of the distal border of the NB and osseous fragments and arthropathy, and between most types of radiographic findings in the NBs and osseous fragments in tarsal joints. CONCLUSIONS AND CLINICAL RELEVANCE: The genetic bases for different types of RNB were not identical. The detection of correlations between normal RNB and findings of short and conical CSs versus deformed CSs and structural and contour changes warrants further study. Genetically justified distinction between physiologic and pathologic NB changes will increase the efficiency of selecting against NBs with radiographically apparent alterations.

Evaluation of expected response to selection for orthopedic health and performance traits in Hanoverian Warmblood horses.

OBJECTIVE: To determine whether selection schemes accounting for orthopedic health traits were compatible with breeding progress in performance parameters in Hanoverian Warmblood horses. ANIMALS: 5,928 horses. PROCEDURE: Relative breeding values (RBVs) were predicted for osseous fragments in fetlock (metacarpo- and metatarsophalangeal) and tarsal joints, deforming arthropathy in tarsal joints, and pathologic changes in distal sesamoid bones. Selection schemes were developed on the basis of total indices for radiographic findings (TIR), dressage (TID), and jumping (TIJ). Response to selection was traced over 2 generations of horses for dressage and jumping ability and all-purpose breeding. Development of mean RBVs and mean total indices in sires and prevalences of orthopedic health traits in their offspring were used to assess response to selection. RESULTS: Giving equal weight toTIR andTID, TIJ, or a combined index of 60% TID and 40% TIJ, 43% to 53% of paternal grandsires and 70% to 82% of descending sires passed selection. In each case, RBVs and total indices increased by as much as 9% in selected sires, when compared with all sires, and prevalences of orthopedic health traits in offspring of selected sires decreased relatively by as much as 16%. When selection was exclusively based on TID, TIJ, or TID and TIJ, percentages of selected sires were 44% to 66% in the first and 73% to 84% in the second generation and TID and TIJ increased by 9% to 10% and 19% to 23%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with exclusively performance-based selection, percentages of selected sires changed slightly and breeding progress in TID, TIJ, or TID and TIJ was only slightly decreased; however, prevalences of orthopedic health traits decreased in offspring of TIR-selected sires.

Skeletal morphology and morphometry of the lumbosacral junction in German shepherd dogs and an evaluation of the possible genetic basis for radiographic findings.

The aim of this study was to identify skeletal variations in the lumbosacral junction (LSJ) of the German shepherd dog (GSD) compared with other large breeds. The radiographic traits of the LSJ were investigated in a group of 733 GSDs and a control group of 334 dogs of other breeds that were matched in terms of size. Nine morphological and 17 morphometric traits were recorded and analysed. Furthermore, the possibility of a genetic basis for these radiographic features was evaluated by calculation of genetic variance components. Five of the morphological and 14 of the morphometric traits varied significantly between the GSD group and the control group (P<0.05). Osteochondrosis of the sacral endplate (SOC) had a higher prevalence in the GSDs (10.1%) compared with controls (5.7%). The majority of LSJ degenerative changes recorded from the radiographs occurred in the GSDs. The extent and relative proportion of lumbosacral step formations were greater in the GSD group compared with controls (P<0.001). The lumbosacral vertebral canal height was reduced in the GSD compared with the control dogs (P<0.001) suggesting a primary stenosis. This was accentuated by an abrupt tapering of the vertebral canal at the level of the LSJ indicated by a lumbosacral ratio of 1.51 in the GSD. The skeletal morphology and morphometry of the LSJ in the GSD seem to be different from that found in other large dogs. For multiple traits frequently observed in GSD such as SOC, step formations, and LSJ stenosis, moderate to high non-zero heritabilities were noted. As these features are also assumed to promote lumbosacral disease, selection against these traits is suggested.

MR-imaging of lumbosacral intervertebral disc degeneration in clinically sound German shepherd dogs compared to other breeds.

German shepherd dogs are overrepresented in the group of dogs with cauda equina compression syndrome due to degenerative lumbosacral stenosis. A congenital predisposition for early degeneration of the lumbosacral intervertebral disc has been suspected. Our aims were to assess the morphologic appearance of the lumbosacral intervertebral disc and the lumbosacral junction in healthy German shepherd dogs compared to other breeds and to evaluate for an early onset of degenerative changes. The lumbosacral spine of 110 clinically sound German shepherd dogs and 47 healthy dogs of other large breeds was examined using magnetic resonance (MR) imaging. The degeneration of every intervertebral disc was graded using an established classification system. Signal intensity of the entire lumbosacral disc and the nucleus pulposus was determined independently. Lumbosacral malalignment was assessed according to a previously described method. The findings for the German shepherd dogs were compared to those of the other breeds. Although most dogs were younger than 18 months at the date of examination, significantly higher grades of degeneration were detected for the lumbosacral intervertebral disc of German shepherd dogs (P < 0.003). Degeneration of the lumbosacral intervertebral disc was independent from findings in the other lumbar discs. We conclude that the German shepherd dog has a predisposition for degenerative changes in the lumbosacral intervertebral disc.