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1.
Sci Rep ; 14(1): 22930, 2024 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358442

RESUMEN

Whole genome sequences (WGS) of 185 North American Thoroughbred horses were compared to quantify the number and frequency of variants, diversity of mitotypes, and autosomal runs of homozygosity (ROH). Of the samples, 82 horses were born between 1965 and 1986 (Group 1); the remaining 103, selected to maximize pedigree diversity, were born between 2000 and 2020 (Group 2). Over 14.3 million autosomal variants were identified with 4.5-5.0 million found per horse. Mitochondrial sequences associated the North American Thoroughbreds with 9 of 17 clades previously identified among diverse breeds. Individual coefficients of inbreeding, estimated from ROH, averaged 0.266 (Group 1) and 0.283 (Group 2). When SNP arrays were simulated using subsets of WGS markers, the arrays over-estimated lengths of ROH. WGS-based estimates of inbreeding were highly correlated (r > 0.98) with SNP array-based estimates, but only moderately correlated (r = 0.40) with inbreeding based on 5-generation pedigrees. On average, Group 1 horses had more heterozygous variants (P < 0.001), more total variants (P < 0.001), and lower individual inbreeding (FROH; P < 0.001) than horses in Group 2. However, the distribution of numbers of variants, allele frequency, and extent of ROH overlapped among all horses such that it was not possible to identify the group of origin of any single horse using these measures. Consequently, the Thoroughbred population would be better monitored by investigating changes in specific variants, rather than relying on broad measures of diversity. The WGS for these 185 horses is publicly available for comparison to other populations and as a foundation for modeling changes in population structure, breeding practices, or the appearance of deleterious variants.


Asunto(s)
Homocigoto , Endogamia , Linaje , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma , Animales , Caballos/genética , Secuenciación Completa del Genoma/métodos , América del Norte , Masculino , Femenino , Genoma , Variación Genética , Cruzamiento
2.
BMC Vet Res ; 20(1): 311, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997753

RESUMEN

BACKGROUND: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour. CONCLUSIONS: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.


Asunto(s)
Analgésicos Opioides , Polimorfismo de Nucleótido Simple , Receptor de Melanocortina Tipo 1 , Animales , Caballos , Analgésicos Opioides/farmacología , Analgésicos Opioides/uso terapéutico , Receptor de Melanocortina Tipo 1/genética , Pigmentación/genética , Proteína de Señalización Agouti/genética , Masculino , Femenino , Fenotipo , Líquido Cefalorraquídeo/metabolismo
3.
Vet Parasitol ; 330: 110219, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38897057

RESUMEN

Equine protozoal myeloencephalitis (EPM) is a challenging disease to diagnose in horses with neurological signs. To optimize contemporary diagnostic testing, including the use of serum:CSF antibody ratios, the SarcoFluor antibody test for Sarcocystis neurona requires revalidation. The SarcoFluor, a previously validated immunofluorescent antibody test (IFAT) for the detection of antibodies specific to S. neurona in serum and cerebrospinal fluid (CSF) of naturally infected horses was analyzed using recent data and considering a serum:CSF antibody ratio threshold. Utilization of serum and CSF phosphorylated neurofilament heavy protein (pNfH) concentrations in support of an EPM diagnosis was also evaluated. 172 horses were divided into three groups: EPM-positive horses (EPM+, n=42), neurological non-EPM horses (n=74) confirmed with non-EPM neurological diseases (cervical vertebral compressive myelopathy, equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy), and control horses (control, n=56) without neurological signs and neurological abnormalities on histology. Logistic regression was used to compare EPM diagnostic regimens. Specifically, EPM+ horses were compared with neurological non-EPM horses showing neurological signs. To consider diagnostic utility, post-test probabilities were calculated by titer. When differentiating between EPM and other neurological diseases, the combination of serum and CSF SarcoFluor testing added more information to the model accuracy than either test alone. Using serum and CSF for pNfH in support of an EPM diagnosis did not identify cutoffs with statistically significant odds ratios but increased the overall model accuracy when used with the IFAT. Utilization of IFAT titers against S. neurona in serum and CSF result in a high post-test probability of detecting EPM+ horses in a clinical setting.


Asunto(s)
Anticuerpos Antiprotozoarios , Enfermedades de los Caballos , Sarcocystis , Sarcocistosis , Animales , Caballos , Sarcocystis/inmunología , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/líquido cefalorraquídeo , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/parasitología , Enfermedades de los Caballos/líquido cefalorraquídeo , Sarcocistosis/veterinaria , Sarcocistosis/diagnóstico , Sarcocistosis/parasitología , Sensibilidad y Especificidad , Técnica del Anticuerpo Fluorescente/veterinaria , Encefalomielitis Equina/veterinaria , Encefalomielitis Equina/diagnóstico , Encefalomielitis Equina/parasitología , Encefalomielitis/veterinaria , Encefalomielitis/parasitología , Encefalomielitis/diagnóstico , Encefalomielitis/líquido cefalorraquídeo
4.
Vet J ; 305: 106129, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38734404

RESUMEN

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disease associated with vitamin E deficiency in the first year of life. It is the second most common cause of spinal ataxia in horses euthanized for neurologic disease. Equine NAD/EDM is characterized by neurologic signs including a symmetric proprioceptive ataxia (> grade 2/5) and a wide-base stance at rest. There are currently no antemortem tests for eNAD/EDM in any breed. Conclusive diagnosis requires postmortem histologic evaluation of the brainstem and spinal cord at necropsy. Research studies on antemortem biomarkers and genetic testing are ongoing. The development of a genetic test for eNAD/EDM would have widespread impact, even if it were breed specific. Currently, the best approach to eNAD/EDM is to focus on preventing cases by providing pregnant mares and foals with access to pasture. Alternatively, dams' diets can be supplemented with high doses of water-soluble RRR-α-tocopherol during the last trimester of gestation, with continued supplementation of foals through the first two years of life. It is important to measure horses' baseline serum vitamin E levels prior to supplementing. While considered generally safe, oversupplementation of vitamin E is possible and can lead to coagulopathies.


Asunto(s)
Enfermedades de los Caballos , Distrofias Neuroaxonales , Deficiencia de Vitamina E , Caballos , Animales , Distrofias Neuroaxonales/veterinaria , Deficiencia de Vitamina E/veterinaria , Deficiencia de Vitamina E/complicaciones , Vitamina E/administración & dosificación , Vitamina E/uso terapéutico , Femenino , Embarazo , Suplementos Dietéticos/análisis
5.
J Vet Intern Med ; 38(3): 1792-1798, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38613444

RESUMEN

BACKGROUND: Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs). OBJECTIVES: To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation. ANIMALS: Twenty-six GVs from 1 farm in California and 2 cases from the Midwestern U.S. METHODS: Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre-supplementation blood vitamin E concentration was assessed in 17- GVs. Twenty-three were supplemented orally with 10 IU/kg of liquid RRR-alpha-tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre-supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM. RESULTS: Pre-supplementation blood vitamin E concentration was ≤2.0 µg/mL in 16/17 (94%) of GVs from California. Post-supplementation concentration varied, with a median of 3.39 µg/mL (range, 1.23-13.87 µg/mL), but only 12/23 (52%) were normal (≥3.0 µg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs.


Asunto(s)
Enfermedades de los Caballos , Distrofias Neuroaxonales , Vitamina E , Animales , Caballos , Distrofias Neuroaxonales/veterinaria , Distrofias Neuroaxonales/genética , Masculino , Femenino , Estudios Prospectivos , Vitamina E/uso terapéutico , Vitamina E/sangre , Suplementos Dietéticos , California , Linaje , Deficiencia de Vitamina E/veterinaria , Deficiencia de Vitamina E/complicaciones
6.
J Vet Intern Med ; 38(3): 1808-1814, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38669583

RESUMEN

BACKGROUND: In 2020, a novel neurologic disease was observed in juvenile Quarter Horses (QHs) in North America. It was unknown if this was an aberrant manifestation of another previously described neurological disorder in foals, such as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). HYPOTHESIS/OBJECTIVES: To describe the clinical findings, outcomes, and postmortem changes with Equine Juvenile Spinocerebellar Ataxia (EJSCA), differentiate the disease from other similar neurological disorders, and determine a mode of inheritance. ANIMALS: Twelve neurologically affected QH foals and the dams. METHODS: Genomic DNA was isolated and pedigrees were manually constructed. RESULTS: All foals (n = 12/12) had a history of acute onset of neurological deficits with no history of trauma. Neurological deficits were characterized by asymmetrical spinal ataxia, with pelvic limbs more severely affected than thoracic limbs. Clinicopathological abnormalities included high serum activity of gamma-glutamyl transferase and hyperglycemia. All foals became recumbent (median, 3 days: [0-18 days]), which necessitated humane euthanasia (n = 11/12, 92%; the remaining case was found dead). Histological evaluation at postmortem revealed dilated myelin sheaths and digestion chambers within the spinal cord, most prominently in the dorsal spinocerebellar tracts. Pedigree analysis revealed a likely autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: EJSCA is a uniformly fatal, rapidly progressive, likely autosomal recessive neurological disease of QHs <1 month of age in North America that is etiologically distinct from other clinically similar neurological disorders. Once the causative variant for EJSCA is validated, carriers can be identified through genetic testing to inform breeding decisions.


Asunto(s)
Enfermedades de los Caballos , Linaje , Animales , Caballos , Enfermedades de los Caballos/genética , Enfermedades de los Caballos/patología , Masculino , Femenino , América del Norte , Ataxias Espinocerebelosas/veterinaria , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología , Enfermedades del Sistema Nervioso/veterinaria , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/patología
7.
bioRxiv ; 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38260378

RESUMEN

Background: Allele-specific expression (ASE) analysis provides a nuanced view of cis-regulatory mechanisms affecting gene expression. Results: In this work, we introduce and highlight the significance of an equine ASE analysis, containing integrated long- and short-read RNA sequencing data, along with insight from histone modification data, from four healthy Thoroughbreds (2 mares and 2 stallions) across 9 tissues. Conclusions: This valuable publicly accessible resource is poised to facilitate investigations into regulatory variation in equine tissues and foster a deeper understanding of the impact of allelic imbalance in equine health and disease at the molecular level.

8.
J Vet Pharmacol Ther ; 47(3): 187-192, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38197553

RESUMEN

There are two FDA-approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses. However, bisphosphonates have a short detection window in the blood before sequestration in the skeleton, making the reliability of current drug tests questionable. Seven exercising Thoroughbred horses were administered clodronate (1.8 mg/kg i.m.), and four were administered saline. RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected immediately before a single dose of clodronate or saline and then on Days 1, 6, 28, 56 and 182 post-dose. mRNA was sequenced and analysed for differentially expressed transcripts. While no single transcripts were differentially expressed, pathway analysis revealed that p38 MAPK (p = .04) and Ras (p = .04) pathways were upregulated, and cadherin signalling (p = .02) was downregulated on Day 1. Previously investigated biomarkers, cathepsin K (CTSK) and type 5 acid phosphatase (ACP5), were analysed with RT-qPCR in a targeted gene approach, with no significant difference observed. A significant effect of time on gene expression for ACP5 (p = .03) and CTSK (p < .0001) was observed. Thus, these genes warrant further investigation for detecting clodronate use over time.


Asunto(s)
Conservadores de la Densidad Ósea , Ácido Clodrónico , Regulación de la Expresión Génica , Animales , Caballos/sangre , Ácido Clodrónico/farmacología , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Femenino , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo
9.
J Vet Intern Med ; 38(1): 417-423, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37937700

RESUMEN

BACKGROUND: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disorder associated with vitamin E deficiency. In humans, polymorphisms in genes involved in vitamin E uptake and distribution determines individual vitamin E requirements. HYPOTHESIS/OBJECTIVES: Genetic polymorphisms in genes involved in vitamin E metabolism would be associated with an increased risk of eNAD/EDM in Quarter Horses (QHs). ANIMALS: Whole-genome sequencing: eNAD/EDM affected (n = 9, postmortem [PM]-confirmed) and control (n = 32) QHs. VALIDATION: eNAD/EDM affected (n = 39, 23-PM confirmed) and control (n = 68, 7-PM confirmed) QHs. Allele frequency (AF): Publicly available data from 504 horses across 47 breeds. METHODS: Retrospective, case control study. Whole-genome sequencing was performed and genetic variants identified within 28 vitamin E candidate genes. These variants were subsequently genotyped in the validation cohort. RESULTS: Thirty-nine confirmed variants in 15 vitamin E candidate genes were significantly associated with eNAD/EDM (P < .01). In the validation cohort, 2 intronic CD36 variants (chr4:726485 and chr4:731082) were significantly associated with eNAD/EDM in clinical (P = 2.78 × 10-4 and P = 4 × 10-4 , respectively) and PM-confirmed cases (P = 6.32 × 10-6 and 1.04 × 10-5 , respectively). Despite the significant association, variant AFs were low in the postmortem-confirmed eNAD/EDM cases (0.22-0.26). In publicly available equine genomes, AFs ranged from 0.06 to 0.1. CONCLUSIONS AND CLINICAL IMPORTANCE: Many PM-confirmed cases of eNAD/EDM were wild-type for the 2 intronic CD36 SNPs, suggesting either a false positive association or genetic heterogeneity of eNAD/EDM within the QH breed.


Asunto(s)
Enfermedades de los Caballos , Distrofias Neuroaxonales , Enfermedades Neurodegenerativas , Humanos , Animales , Caballos/genética , Vitamina E , Estudios de Casos y Controles , Estudios Retrospectivos , Distrofias Neuroaxonales/genética , Distrofias Neuroaxonales/veterinaria , Ataxia/veterinaria , Polimorfismo de Nucleótido Simple , Enfermedades Neurodegenerativas/veterinaria , Enfermedades de los Caballos/genética
10.
Int J Parasitol ; 54(1): 23-32, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37536388

RESUMEN

Cyathostomins are ubiquitous equine nematodes. Infection can result in larval cyathostominosis due to mass larval emergence. Although faecal egg count (FEC) tests provide estimates of egg shedding, these correlate poorly with burden and provide no information on mucosal/luminal larvae. Previous studies describe a serum IgG(T)-based ELISA (CT3) that exhibits utility for detection of mucosal/luminal cyathostomins. Here, this ELISA is optimised/validated for commercial application using sera from horses for which burden data were available. Optimisation included addition of total IgG-based calibrators to provide standard curves for quantification of antigen-specific IgG(T) used to generate a CT3-specific 'serum score' for each horse. Validation dataset results were then used to assess the optimised test's performance and select serum score cut-off values for diagnosis of burdens above 1000, 5000 and 10,000 cyathostomins. The test demonstrated excellent performance (Receiver Operating Characteristic Area Under the Curve values >0.9) in diagnosing infection, with >90% sensitivity and >70% specificity at the selected serum score cut-off values. CT3-specific serum IgG(T) profiles in equines in different settings were assessed to provide information for commercial test use. These studies demonstrated maternal transfer of CT3-specific IgG(T) in colostrum to newborns, levels of which declined before increasing as foals consumed contaminated pasture. Studies in geographically distinct populations demonstrated that the proportion of horses that reported as test positive at a 14.37 CT3 serum score (1000-cyathostomin threshold) was associated with parasite transmission risk. Based on the results, inclusion criteria for commercial use were developed. Logistic regression models were developed to predict probabilities that burdens of individuals are above defined thresholds based on the reported serum score. The models performed at a similar level to the serum score cut-off approach. In conclusion, the CT3 test provides an option for veterinarians to obtain evidence of low cyathostomin burdens that do not require anthelmintic treatment and to support diagnosis of infection.


Asunto(s)
Antihelmínticos , Enfermedades de los Caballos , Infecciones Equinas por Strongyloidea , Caballos , Animales , Infecciones Equinas por Strongyloidea/tratamiento farmacológico , Enfermedades de los Caballos/parasitología , Antihelmínticos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunoglobulina G , Recuento de Huevos de Parásitos/veterinaria , Heces/parasitología
11.
J Alzheimers Dis ; 96(3): 1129-1138, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37955092

RESUMEN

BACKGROUND: The association of different types of tocopherols (vitamin E) with cognition might vary by the APOEɛ4 allele status. OBJECTIVE: We examined the association of dietary tocopherols with cognitive decline among participants with and without the APOEɛ4 allele over a median of 12 years. METHODS: 2,193 participants from the Chicago Health and Aging Project were included in the analyses. Global cognition was assessed in three-year cycles. We used a 144-item FFQ to assess dietary intakes of tocopherols and hME Sequenom mass-array platform to assess APOE genotype. We used linear mixed effects models to examine the relationship between tocopherol from food sources and global cognitive decline. RESULTS: The mean baseline age was 74.1 (SD = 5.9) years. Among APOEɛ4 carriers, participants in the highest quintile of intakes of dietary vitamin E had a slower cognitive decline of 0.022 SDU (95% CI: 0.000, 0.043) compared to those in the lowest quintile. A higher intake of dietary α-tocopherol from food sources only was associated with slower cognitive decline in APOEɛ4 carriers (p for trend 0.002) but not among the non-carriers (p for trend 0.937). Among APOEɛ4 carriers, those in the highest quintile of intake of α-tocopherol had a 16.4% slower rate of decline of global cognition compared to those in the lowest quintile (ß= 0.034, 95% CI: 0.013, 0.054). CONCLUSIONS: Individuals consuming high α-tocopherol from food sources had slower cognitive decline among APOEɛ4 carriers. In older adults, different forms of vitamin E might moderate the relationship of APOEɛ4 with global cognition.


Asunto(s)
Disfunción Cognitiva , Vitamina E , Humanos , Anciano , alfa-Tocoferol , Alelos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/genética , Tocoferoles , Apolipoproteína E4/genética
12.
Vet Ophthalmol ; 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37815029

RESUMEN

Congenital stationary night blindness (CSNB) is an ocular disorder characterized by nyctalopia. An autosomal recessive missense mutation in glutamate metabotropic receptor 6 (GRM6 c.533C>T, p.(Thr178Met)), called CSNB2, was previously identified in one Tennessee Walking Horse and predicted to reduce binding affinity of the neurotransmitter glutamate, impacting the retinal rod ON-bipolar cell signaling pathway. Thus, the first aim was to identify the allele frequency (AF) of CSNB2 in breeds with reported cases of CSNB and breeds closely related to the Tennessee Walking Horse. The second aim was to perform ocular examinations in multiple breeds to confirm the link between genotype and CSNB phenotype. In evaluating 3518 horses from 14 breeds, the CSNB2 allele was identified in nine previously unreported breeds. The estimated AF was highest in pacing Standardbreds (0.17) and lowest in American Quarter Horses (0.0010). Complete ophthalmic examinations and electroretinograms (ERG) were performed on 19 horses from three breeds, including one CSNB2 homozygote from each breed. All three CSNB2/CSNB2 horses had an electronegative ERG waveform under scotopic light conditions consistent with CSNB. The remaining 16 horses (seven CSNB2/N and nine N/N) had normal scotopic ERG results. All horses had normal photopic ERGs. This study provides additional evidence that GRM6 c.533C>T homozygosity is likely causal to CSNB in Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses. Genetic testing is recommended for breeds with the CSNB2 allele to limit the production of affected horses. This study represents the largest across-breed identification of CSNB in the horse and suggests that this disorder is likely underdiagnosed.

13.
J Vet Intern Med ; 37(6): 2529-2534, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37775973

RESUMEN

BACKGROUND: Omega-3 fatty acid and alpha-tocopherol supplementation reduces gastric ulcer formation in humans and rodents; however, efficacy of prevention in horses is unknown. Equine Omega Complete (EOC) is an oral supplement containing omega-3 fatty acids and alpha-tocopherol. HYPOTHESIS/OBJECTIVE: Determine if EOC supplementation prevents gastric ulcers and increases serum alpha-tocopherol concentrations in healthy horses. ANIMALS: Nine thoroughbred geldings; 5-13 years old. METHODS: Prospective randomized block design, repeated in crossover model. Horses were administered EOC, omeprazole, or water PO for 28 days. Horses underwent an established gastric ulcer induction protocol from days 21-28 via intermittent feed deprivation. Gastroscopies were performed on days 0, 21, and 28. Serum alpha-tocopherol concentrations were measured on days 0 and 28. The effects of treatment and time on ulcer grades were assessed with ordinal logistic regression, with significance at P-value <.05. RESULTS: Ulcer grades increased during ulcer induction in control and EOC but not omeprazole groups (P = .02). Grades increased in EOC-treated horses after ulcer induction from a median of 1 [95% confidence interval 0-2.5] (day 0) to 2.5 [1.5-3.5] (day 28) and were similar to the control group (P = .54). Serum alpha-tocopherol increased in EOC-treated horses from day 0 to day 28 (mean 2.2 ± 0.43 µg/mL to 2.96 ± 0.89 µg/mL; P < .001) with high individual variation; this increase was not different from omeprazole or control groups. CONCLUSION AND CLINICAL IMPORTANCE: Supplementation with EOC for 28 days did not prevent gastric ulcer formation nor increase alpha-tocopherol concentrations relative to the control group.


Asunto(s)
Enfermedades de los Caballos , Úlcera Gástrica , alfa-Tocoferol , Animales , Masculino , alfa-Tocoferol/administración & dosificación , alfa-Tocoferol/sangre , Estudios Cruzados , Suplementos Dietéticos , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/prevención & control , Caballos , Omeprazol/administración & dosificación , Estudios Prospectivos , Úlcera Gástrica/sangre , Úlcera Gástrica/prevención & control , Úlcera Gástrica/veterinaria
14.
Commun Biol ; 6(1): 963, 2023 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735603

RESUMEN

Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence of the ECA11 centromeric region in the EquCab3.0 assembly. Then, to test whether centromere sliding may occur during development, we map the CENP-A binding domains of ECA11 using ChIP-seq in five tissues of different embryonic origin from the four horses of the equine FAANG (Functional Annotation of ANimal Genomes) consortium. Our results demonstrate that the centromere is localized in the same region in all tissues, suggesting that the position of the centromeric domain is maintained during development.


Asunto(s)
Centrómero , ADN Satélite , Humanos , Animales , Caballos , Proteína A Centromérica/genética , Centrómero/genética , Histonas , Meiosis , Mamíferos
15.
J Vet Intern Med ; 37(4): 1568-1579, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37288990

RESUMEN

BACKGROUND: Shivers in horses is characterized by abnormal hindlimb movement when walking backward and is proposed to be caused by a Purkinje cell (PC) axonopathy based on histopathology. OBJECTIVES: Define region-specific differences in gene expression within the lateral cerebellar hemisphere and compare cerebellar protein expression between Shivers horses and controls. ANIMALS: Case-control study of 5 Shivers and 4 control geldings ≥16.2 hands in height. METHODS: Using spatial transcriptomics, gene expression was compared between Shivers and control horses in PC soma and lateral cerebellar hemisphere white matter, consisting primarily of axons. Tandem-mass-tag (TMT-11) proteomic analysis was performed on lateral cerebellar hemisphere homogenates. RESULTS: Differences in gene expression between Shivers and control horses were evident in principal component analysis of axon-containing white matter but not PC soma. In white matter, there were 455/1846 differentially expressed genes (DEG; 350 ↓DEG, 105 ↑DEG) between Shivers and controls, with significant gene set enrichment of the Toll-Like Receptor 4 (TLR4) cascade, highlighting neuroinflammation. There were 50/936 differentially expressed proteins (DEP). The 27 ↓DEP highlighted loss of axonal proteins including intermediate filaments (5), myelin (3), cytoskeleton (2), neurite outgrowth (2), and Na/K ATPase (1). The 23 ↑DEP were involved in the extracellular matrix (7), cytoskeleton (7), redox balance (2), neurite outgrowth (1), signal transduction (1), and others. CONCLUSION AND CLINICAL IMPORTANCE: Our findings support axonal degeneration as a characteristic feature of Shivers. Combined with histopathology, these findings are consistent with the known distinctive response of PC to injury where axonal changes occur without a substantial impact on PC soma.


Asunto(s)
Proteómica , Transcriptoma , Masculino , Animales , Caballos , Estudios de Casos y Controles , Células de Purkinje/patología , Axones/patología
16.
Int J Mol Sci ; 24(8)2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37108254

RESUMEN

The placenta is a temporary organ that is essential for the survival of the fetus, with a lifelong effect on the health of both the offspring and the dam. The functions of the placenta are controlled by its dynamic gene expression during gestation. In this study, we aimed to investigate the equine placental DNA methylome as one of the fundamental mechanisms that controls the gene expression dynamic. Chorioallantois samples from four (4M), six (6M), and ten (10M) months of gestation were used to map the methylation pattern of the placenta. Globally, methylation levels increased toward the end of gestation. We identified 921 differentially methylated regions (DMRs) between 4M and 6M, 1225 DMRs between 4M and 10M, and 1026 DMRs between 6M and 10M. A total of 817 genes carried DMRs comparing 4M and 6M, 978 comparing 4M and 10M, and 804 comparing 6M and 10M. We compared the transcriptomes between the samples and found 1381 differentially expressed genes (DEGs) when comparing 4M and 6M, 1428 DEGs between 4M and 10M, and 741 DEGs between 6M and 10M. Finally, we overlapped the DEGs and genes carrying DMRs (DMRs-DEGs). Genes exhibiting (a) higher expression, low methylation and (b) low expression, high methylation at different time points were identified. The majority of these DMRs-DEGs were located in introns (48.4%), promoters (25.8%), and exons (17.7%) and were involved in changes in the extracellular matrix; regulation of epithelial cell migration; vascularization; and regulation of minerals, glucose, and metabolites, among other factors. Overall, this is the first report highlighting the dynamics in the equine placenta methylome during normal pregnancy. The findings presented serve as a foundation for future studies on the impact of abnormal methylation on the outcomes of equine pregnancies.


Asunto(s)
Metilación de ADN , Placenta , Embarazo , Animales , Femenino , Caballos/genética , Placenta/metabolismo , Transcriptoma , Epigenoma , Feto/metabolismo , Epigénesis Genética
17.
PLoS Genet ; 19(3): e1010468, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36862752

RESUMEN

The genomic sequence of the horse has been available since 2009, providing critical resources for discovering important genomic variants regarding both animal health and population structures. However, to fully understand the functional implications of these variants, detailed annotation of the horse genome is required. Due to the limited availability of functional data for the equine genome, as well as the technical limitations of short-read RNA-seq, existing annotation of the equine genome contains limited information about important aspects of gene regulation, such as alternate isoforms and regulatory elements, which are either not transcribed or transcribed at a very low level. To solve above problems, the Functional Annotation of the Animal Genomes (FAANG) project proposed a systemic approach to tissue collection, phenotyping, and data generation, adopting the blueprint laid out by the Encyclopedia of DNA Elements (ENCODE) project. Here we detail the first comprehensive overview of gene expression and regulation in the horse, presenting 39,625 novel transcripts, 84,613 candidate cis-regulatory elements (CRE) and their target genes, 332,115 open chromatin regions genome wide across a diverse set of tissues. We showed substantial concordance between chromatin accessibility, chromatin states in different genic features and gene expression. This comprehensive and expanded set of genomics resources will provide the equine research community ample opportunities for studies of complex traits in the horse.


Asunto(s)
Genoma , Caballos , Transcriptoma , Caballos/genética , Animales , Anotación de Secuencia Molecular , Especificidad de Órganos , Cromatina , Elementos Reguladores de la Transcripción , Sitio de Iniciación de la Transcripción , Análisis de Secuencia de ARN , Regulación de la Expresión Génica
18.
J Vet Intern Med ; 37(2): 689-696, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36929645

RESUMEN

BACKGROUND: Cervical vertebral compressive myelopathy (CVCM) and equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) are leading causes of spinal ataxia in horses. The conditions can be difficult to differentiate, and there is currently no diagnostic modality that offers a definitive antemortem diagnosis. OBJECTIVE: Evaluate novel proteomic techniques and machine learning algorithms to predict biomarkers that can aid in the antemortem diagnosis of noninfectious spinal ataxia in horses. ANIMALS: Banked serum and cerebrospinal fluid (CSF) samples from necropsy-confirmed adult eNAD/EDM (n = 47) and CVCM (n = 25) horses and neurologically normal adult horses (n = 45). METHODS: . A subset of serum and CSF samples from eNAD/EDM (n = 5) and normal (n = 5) horses was used to evaluate the proximity extension assay (PEA). All samples were assayed by PEA for 368 neurologically relevant proteins. Data were analyzed using machine learning algorithms to define potential diagnostic biomarkers. RESULTS: Of the 368 proteins, 84 were detected in CSF and 146 in serum. Eighteen of 84 proteins in CSF and 30/146 in serum were differentially abundant among the 3 groups, after correction for multiple testing. Modeling indicated that a 2-protein test using CSF had the highest accuracy for discriminating among all 3 groups. Cerebrospinal fluid R-spondin 1 (RSPO1) and neurofilament-light (NEFL), in parallel, predicted normal horses with an accuracy of 87.18%, CVCM with 84.62%, and eNAD/EDM with 73.5%. MAIN LIMITATIONS: Cross-species platform. Uneven sample size. CONCLUSIONS AND CLINICAL IMPORTANCE: Proximity extension assay technology allows for rapid screening of equine biologic matrices for potential protein biomarkers. Machine learning analysis allows for unbiased selection of highly accurate biomarkers from high-dimensional data.


Asunto(s)
Enfermedades de los Caballos , Distrofias Neuroaxonales , Enfermedades Neurodegenerativas , Compresión de la Médula Espinal , Enfermedades de la Médula Espinal , Animales , Caballos , Compresión de la Médula Espinal/diagnóstico , Compresión de la Médula Espinal/veterinaria , Proteómica , Enfermedades de la Médula Espinal/veterinaria , Distrofias Neuroaxonales/diagnóstico , Distrofias Neuroaxonales/veterinaria , Ataxia/veterinaria , Enfermedades Neurodegenerativas/veterinaria , Biomarcadores , Enfermedades de los Caballos/diagnóstico
19.
Equine Vet J ; 55(5): 884-890, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36516303

RESUMEN

BACKGROUND: Phosphorylated neurofilament heavy, a marker of neuroaxonal damage, is increased in horses with equine neuroaxonal dystrophy. However, the temporal dynamics of this biomarker during the post-natal risk period are not understood. OBJECTIVE: To measure serum and cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile foals across the post-natal window of susceptibility for equine neuroaxonal dystrophy. STUDY DESIGN: Case-control in vivo experimental study. METHODS: Concentrations of phosphorylated neurofilament heavy were measured using frozen serum and cerebrospinal fluid collected from 13 foals raised in a vitamin E deficient environment from 1 to 6 months of age. Four of these foals were produced by equine neuroaxonal dystrophy-affected dams, developed clinical signs consistent with equine neuroaxonal dystrophy and had a diagnosis confirmed by histopathology. The remaining nine foals, produced by healthy mares, were vitamin E depleted and remained clinically healthy. An additional cohort of foals, produced by healthy mares, were supplemented with vitamin E (α-tocopherol; α-TOH) from birth and sampled similarly. RESULTS: Serum α-TOH concentrations were significantly higher in vitamin E supplemented healthy foals. Serum phosphorylated neurofilament heavy concentrations did not differ significantly between groups at any time point. Cerebrospinal fluid phosphorylated neurofilament heavy concentrations increased with age in healthy vitamin E depleted foals (p < 0.001); an effect that was not observed in healthy vitamin E supplemented foals. MAIN LIMITATIONS: A genetically susceptible cohort supplemented with vitamin E was not available for comparison. CONCLUSION: We demonstrate that vitamin E depletion may elevate cerebrospinal fluid phosphorylated neurofilament heavy in otherwise healthy juvenile foals by 6 months of age. We highlight an important cofactor to consider when interpreting cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile horses.


Asunto(s)
Enfermedades de los Caballos , Distrofias Neuroaxonales , Animales , Caballos , Femenino , Vitamina E , alfa-Tocoferol/líquido cefalorraquídeo , Suplementos Dietéticos , Distrofias Neuroaxonales/veterinaria , Vitaminas
20.
J Equine Vet Sci ; 121: 104192, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36516894

RESUMEN

Gastric ulceration can be induced by athletic training and is a significant welfare concern. The objective of this study was to evaluate the effect of gastric ulcer induction on heart rate variability (HRV) in the horse. We hypothesized that induction of gastric ulcers would decrease HRV and increase low frequency fluctuations, consistent with increased sympathetic tone. A convenience sample of 8 horses in a larger study were enrolled. Horses were randomly assigned to receive water or 2 mg/kg omeprazole orally once daily for 28 days. Gastric ulcers were induced through intermittent feed withholding on days 21 to 28. Gastroscopy was performed and gastric ulcers were graded (0-IV) by three blinded reviewers on days 21 and 28. Continuous electrocardiograms were obtained for one hour at the start and end of ulcer induction. HRV was assessed in 1-hour recordings for time domain variables and 5 minute sections for frequency domain analysis. HRV and ulcer grade across treatments were compared by a mixed effect model, with treatment and time as fixed effects and horse as a random effect. Gastric ulcer grade increased with induction protocol (P < .0001) and decreased with omeprazole treatment (P = .0007). Omeprazole treatment increased R-R intervals (P = .01) and decreased ratio of low frequency/high frequency signal (P = .008) as compared to horses receiving water. This was attributable to decreasing low frequency fluctuations (P = .05). While limited by the small sample size (four horses/treatment), this study suggests that omeprazole treatment decreases heart rate, and LF/HF ratio during ulcer induction, consistent with a decrease in sympathetic tone.


Asunto(s)
Antiulcerosos , Enfermedades de los Caballos , Úlcera Gástrica , Caballos , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/veterinaria , Antiulcerosos/uso terapéutico , Frecuencia Cardíaca , Úlcera/tratamiento farmacológico , Úlcera/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Omeprazol/uso terapéutico
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