Recurrent Airway Obstruction and Summer Pasture‐Associated Obstructive Pulmonary Disease

Bullone, Michela; Lavoie, Jean‐Pierre

doi:10.1002/9781119086512.ch16

Cited by 5 publications

(5 citation statements)

References 180 publications

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“…Dietary histamines can cause allergic symptoms, gastrointestinal ailments, inflammatory responses, as well as a variety of other symptoms in histamine intolerant patients [26]. Histamine is present in respirable hay dust, and has been implicated as an irritating agent that contributes to respiratory problems, and is an inflammatory mediator secreted by IgE activated mast cells [27,28]. Cholesterol biosynthesis was also influenced by HDE treatment.…”

Section: Discussionmentioning

confidence: 99%

PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

Leeb

Gerber

2019

Preprint

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Expression quantitative trait loci (eQTLs) are context dependent, and therefore change 12 between tissues, cell types, and after cell treatment. In addition, SNP positions and RNAseq counts 13 must be updated after assembly of new reference genome sequences. Therefore, we remapped 14 eQTLs with Matrix eQTL using the previously generated and publicly available data from four 15 contexts of peripheral blood mononuclear cells (PBMCs) from European Warmblood horses to the 16 EquCab3.0 reference genome, and used a linear mixed model in R to identify eQTLs with 17 significantly different gene expression regulation in treated PBMCs when compared to no treatment 18 (baseline). We found no evidence that SNPs associated with significant changes in gene expression 19 between MCK and a treatment in PBMCs caused strong opposing regulatory effects. We identified 20 canonical pathways with a significant number of genes in PBMCs with altered gene expression 21 regulation when treated with lipopolysaccharides (LPS) and hay-dust extract (HDE). Significant 22 pathways included RhoA signaling in LPS, as well as histamine degradation, cholesterol 23 biosynthesis, FcγRIIB signaling, and others in HDE. Our results support previous research 24 indicating that pathways altered between baseline and treatment of PBMCs in horses with LPS or 25 HDE affect inflammatory responses through RhoA, B-cell signaling, IL-4 and IFN-γ, and histamine.26

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Section: Discussionmentioning

confidence: 99%

PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

Leeb

Gerber

2019

Preprint

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“…RAO) is a chronic, potentially debilitating airway disease affecting 10–15% of horses housed in conventional management systems in temperate climates [ 1 – 3 ]. It has many important parallels to human asthma, including genetic effects that predispose affected horses to exaggerated mixed T helper cell (T h 1, T h 2, T h 17) responses to common allergens and irritants [ 2 – 4 ]. Environmental irritants from dry hay or dust from various bedding materials contain antigens that elicit severe equine asthma as a delayed hypersensitivity disorder in the domestic horse Equus ferus caballus [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has many important parallels to human asthma, including genetic effects that predispose affected horses to exaggerated mixed T helper cell (T h 1, T h 2, T h 17) responses to common allergens and irritants [ 2 – 4 ]. Environmental irritants from dry hay or dust from various bedding materials contain antigens that elicit severe equine asthma as a delayed hypersensitivity disorder in the domestic horse Equus ferus caballus [ 3 , 4 ]. RAO is maintained until the animal is removed from the offending environment for an extended period [ 5 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…RAO is maintained until the animal is removed from the offending environment for an extended period [ 5 – 8 ]. RAO is reversible, such that when sources of dust are eliminated from the environment clinical signs abate [ 4 ]. To simulate a systemic response to these antigens our group previously treated peripheral blood mononuclear cells (PBMCs) with hay dust extract (HDE), a mixture containing mold spores, mites, inorganic dust particles, and plant fragments [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

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eQTL discovery and their association with severe equine asthma in European Warmblood horses

et al. 2018

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BackgroundSevere 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.ResultsWe 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.ConclusionsThousands 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.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4938-9) contains supplementary material, which is available to authorized users.

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“…In addition to dermatological signs, horses can also develop respiratory issues that may be associated with environmental exposure to certain airborne allergens . In the southeastern United States, summer pasture‐associated obstructive pulmonary disease (SPAOPD) is a condition seen in horses kept outdoors .…”

Section: Introductionmentioning

confidence: 99%