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Caudal cervical vertebral morphological variation is not associated with clinical signs in Warmblood horses.

ABSTRACT: BACKGROUND:Variation in equine caudal cervical spine morphology at C6 and C7 has high prevalence in Warmblood horses and is suspected to be associated with pain in a large mixed-breed group of horses. At present no data exist on the relationship between radiographic phenotype and clinical presentation in Warmblood horses in a case-control study. OBJECTIVES:To establish the frequency of radiographically visible morphologic variation in a large group of Warmblood horses with clinical signs and compare this with a group without clinical signs. We hypothesised that occurrence of morphologic variation in the case group would not differ from the control group, indicating there is no association between clinical signs and morphologic variation. STUDY DESIGN:Retrospective case-control. METHODS:Radiographic presence or absence of morphologic variation of cervical vertebrae C6 and C7 was recorded in case (n = 245) and control horses (n = 132). Case and control groups were compared by univariable Pearson's Chi-square and multivariable logistic regression for measurement variables age, sex, breed, degenerative joint disease and morphologic variation at C6 and C7. Odds ratio and confidence intervals were obtained. A P?0.05 was considered statistically significant. RESULTS:Morphologic variation at C6 and C7 (n = 108/377 = 28.6%; Cases 58/245 = 23.7%; Control 50/132 = 38%) was less frequent in horses with clinical signs in univariable testing (OR 0.48, 95% CI 0.3-0.8, P = 0.001). Age, sex, breed and degenerative joint disease were not retained in the final multivariable logistic regression step whereas morphologic variation remained significantly less present in horses with clinical signs. MAIN LIMITATIONS:Possible demographic differences between equine clinics. CONCLUSIONS:Morphologic variation in the caudal cervical spine was detected more frequently in horses without clinical signs. Therefore, radiographic presence of such variation does not necessarily implicate the presence of clinical signs.

SUBMITTER: Veraa S

PROVIDER: S-EPMC7027909 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Caudal cervical vertebral morphological variation is not associated with clinical signs in Warmblood horses.

Veraa S S de Graaf K K Wijnberg I D ID Back W W Vernooij H H Nielen M M Belt A J M AJM

Equine veterinary journal 20190716 2

<h4>Background</h4>Variation in equine caudal cervical spine morphology at C6 and C7 has high prevalence in Warmblood horses and is suspected to be associated with pain in a large mixed-breed group of horses. At present no data exist on the relationship between radiographic phenotype and clinical presentation in Warmblood horses in a case-control study.<h4>Objectives</h4>To establish the frequency of radiographically visible morphologic variation in a large group of Warmblood horses with clinica ...[more]

PMID: 31211852

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Project description:BACKGROUND:To report a novel exertional myopathy, myofibrillar myopathy (MFM) in Warmblood (WB) horses. OBJECTIVES:To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses and 2) investigate the potential inheritance of MFM in a Warmblood family. STUDY DESIGN:Retrospective selection of MFM cases and prospective evaluation of a Warmblood family. METHODS:Retrospectively, muscle biopsies were selected from Warmblood horses diagnosed with MFM and clinical histories obtained (n = 10). Prospectively, muscle biopsies were obtained from controls (n = 8) and a three generation WB family (n = 11). Samples were assessed for histopathology [scored 0-3], fibre types, cytoskeletal and Z disc protein aggregates, electron microscopic alterations (EM) and muscle glycogen concentrations. RESULTS:Myofibrillar myopathy-affected cases experienced exercise intolerance, reluctance to go forward, stiffness and poorly localised lameness. Abnormal aggregates of the cytoskeletal protein desmin were found in up to 120 type 2a and a few type 2x myofibres of MFM cases. Desmin positive fibres did not stain for developmental myosin, α actinin or dystrophin. Scores for internalised myonuclei (score MFM 0.83 ± 0.67, controls 0.22 ± 0.45), anguloid atrophy (MFM 0.95 ± 0.55, controls 0.31 ± 0.37) and total myopathic scores (MFM 5.85 ± 2.10, controls 1.41 ± 2.17) were significantly higher in MFM cases vs. CONTROLS:Focal Z disc degeneration, myofibrillar disruption and accumulation of irregular granular material was evident in MFM cases. Muscle glycogen concentrations were similar between MFM cases and controls. In the Warmblood family, desmin positive aggregates were found in myofibres of the founding dam and in horses from two subsequent generations. MAIN LIMITATIONS:Restricted sample size due to limited availability of well phenotyped cases. CONCLUSIONS:A distinctive and potentially heritable form of MFM exists in Warmblood horses that present with exercise intolerance and abnormal hindlimb gait. Muscle tissue is characterised by ectopic accumulation of desmin and Z disc and myofibrillar degeneration.

Project description:BACKGROUND:Severe equine asthma, also known as recurrent airway obstruction (RAO), is a debilitating, performance limiting, obstructive respiratory condition in horses that is phenotypically similar to human asthma. Past genome wide association studies (GWAS) have not discovered coding variants associated with RAO, leading to the hypothesis that causative variant(s) underlying the signals are likely non-coding, regulatory variant(s). Regions of the genome containing variants that influence the number of expressed RNA molecules are expression quantitative trait loci (eQTLs). Variation associated with RAO that also regulates a gene's expression in a disease relevant tissue could help identify candidate genes that influence RAO if that gene's expression is also associated with RAO disease status. RESULTS:We searched for eQTLs by analyzing peripheral blood mononuclear cells (PBMCs) from two half-sib families and one unrelated cohort of 82 European Warmblood horses that were previously treated in vitro with: no stimulation (MCK), lipopolysaccharides (LPS), recombinant cyathostomin antigen (RCA), and hay-dust extract (HDE). We identified high confidence eQTLs that did not violate linear modeling assumptions and were not significant due to single outlier individuals. We identified a mean of 4347 high confidence eQTLs in four treatments of PBMCs, and discovered two trans regulatory hotspots regulating genes involved in related biological pathways. We corroborated previous RAO associated single nucleotide polymorphisms (SNPs), and increased the resolution of past GWAS by analyzing 1,056,195 SNPs in 361 individuals. We identified four RAO-associated SNPs that only regulate gene expression of dexamethasone-induced protein (DEXI), however we found no significant association between DEXI gene expression and presence of RAO. CONCLUSIONS:Thousands of genetic variants regulate gene expression in PBMCs of European Warmblood horses in cis and trans. Most high confidence eSNPs are significantly enriched near the transcription start sites of their target genes. Two trans regulatory hotspots on chromosome 11 and 13 regulate many genes involved in transmembrane cell signaling and neurological development respectively when PBMCs are treated with HDE. None of the top fifteen RAO associated SNPs strongly influence disease status through gene expression regulation.

Dataset Information

Caudal cervical vertebral morphological variation is not associated with clinical signs in Warmblood horses.

Publications

Caudal cervical vertebral morphological variation is not associated with clinical signs in Warmblood horses.

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