Identification of genomic loci associated with Rhodococcus equi susceptibility in foals
Ontology highlight
ABSTRACT:
ORGANISM(S): Equus caballus
PROVIDER: GSE57510 | GEO | 2014/05/10
SECONDARY ACCESSION(S): PRJNA246572
REPOSITORIES: GEO
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Project description:aCGH performed to identify copy number variants in Quarter Horses and perform casec-control GWAS Two-condition experiment, All samples were compared to a single Quarter Horse reference to identify copy number variants to be used in the CNV GWAS
2014-05-10 | E-GEOD-57510 | biostudies-arrayexpress
Project description:Pneumonia caused by Rhodococcus equi is a common cause of disease and death in foals. Although agent and environmental factors contribute to the incidence of this disease, the genetic factors influencing the clinical outcomes of R. equi pneumonia are ill-defined. Here, we performed independent single nucleotide polymorphism (SNP)- and copy number variant (CNV)-based genome-wide association studies to identify genomic loci associated with R. equi pneumonia in foals. Foals at a large Quarter Horse breeding farm were categorized into 3 groups: 1) foals with R. equi pneumonia (clinical group [N = 43]); 2) foals with ultrasonographic evidence of pulmonary lesions that never developed clinical signs of pneumonia (subclinical group [N = 156]); and, 3) foals without clinical signs or ultrasonographic evidence of pneumonia (unaffected group [N = 49]). From each group, 24 foals were randomly selected and used for independent SNP- and CNV-based genome-wide association studies (GWAS). The SNP-based GWAS identified a region on chromosome 26 that had moderate evidence of association with R. equi pneumonia when comparing clinical and subclinical foals. A joint analysis including all study foals revealed a 3- to 4-fold increase in odds of disease for a homozygous SNP within the associated region when comparing the clinical group with either of the other 2 groups of foals or their combination. The region contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) gene, which is involved in neutrophil function. No associations were identified in the CNV-based GWAS. Collectively, these data identify a region on chromosome 26 associated with R. equi pneumonia in foals, providing evidence that genetic factors may indeed contribute to this important disease of foals.
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Project description:Investigating genome-wide characteristics of CNVs in 6 horses representing 6 distinct breeds by using the aCGH method and performed GO and KEGG analysis for the CNVs genes.This result is an important complement to the mapping of horse whole-genome CNVs and helpful to study plateau horses’ adaption to the plateau’s environment.
2014-02-26 | GSE52504 | GEO
Project description:The array comparative genomic hybridization (aCGH) was perform to identify regions with genomic imbalance in lung cancer.The aCGH analysis detected a total of 325 regions with genomic imbalance in all 8 lung cancer samples, ranging from focal rearrangements (70 kb–5 Mb) to chromosome-arm alterations with chromosomal segments amplification or deletion. Among these mutations, a total of 115 genomic imbalances were discovered occurring at high frequency varying from 25% to 50%.
2016-11-17 | GSE89927 | GEO
Project description:Rhodococcus equi is an important pathogen of foals that causes severe pneumonia. To date, there is no licensed vaccine effective against R. equi pneumonia of foals. The objectives of our study were to develop an electron beam (eBeam) inactivated vaccine against R. equi and evaluate its immunogenicity. A dose of eBeam irradiation that inactivated replication of R. equi while maintaining outer cell wall integrity was identified. Enteral administration of eBeam inactivated R. equi increased interferon-γ production by peripheral blood mononuclear cells in response to stimulation with virulent R. equi and generated naso-pharyngeal R. equi-specific IgA in newborn foals. Our results indicate that eBeam irradiated R. equi administered enterally produce cell-mediated and upper respiratory mucosal immune responses, in the face of passively transferred maternal antibodies, similar to those produced in response to enteral administration of live organisms (a strategy which previously has been documented to protect foals against intrabronchial infection with virulent R. equi). No evidence of adverse effects was noted among vaccinated foals.
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Project description:Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of age were infected intratracheally with virulent R. equi using inocula of 1×108 CFU (high inoculum; n = 16) or 1×107 CFU (low inoculum; n = 12). Foals were monitored twice daily and necropsy was performed 14 days post-infection. Aqueous humor and synovial fluid were collected aseptically and the percentage of affected lung was calculated. The mean (± SD) percentage of affected lung was significantly higher with the high inoculum (31.8 ± 14.6%) than with the low inoculum (14.4 ± 11.4%). Fourteen of 25 foals developed uveitis and 20 of 28 foals developed polysynovitis. R. equi was cultured from the aqueous humor of 11 foals and from the synovial fluid of 14 foals. The risk of development of polysynovitis and protein concentration in the aqueous humor were significantly higher in foals that received the high inoculum. These results indicate that polysynovitis and uveitis are septic complications associated with the severity of lung disease.
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Project description:Rhodococcus equi (R. equi) is an intracellular bacterium that affects young foals and immuno-compromised individuals causing severe pneumonia. Currently, the genetic mechanisms that confer susceptibility and/or resistance to R. equi are not fully understood. Previously, using a SNP-based genome-wide association study, we identified a region on equine chromosome 26 associated with culture-confirmed clinical pneumonia. To better characterize this region and understand the function of the SNP located within TRPM2 that was associated with R. equi pneumonia, we performed RNA-Seq on 12 horses representing the 3 genotypic forms of this SNP.We identified differentially expressed genes in the innate immune response pathway when comparing homozygous A allele horses with the AB and BB horses. Isoform analyses of the RNA-Seq data predicted the existence of multiple transcripts and provided evidence of differential expression at the TRPM2 locus. This finding is consistent with previously demonstrated work in human cell lines in which isoform-specific expression of TRPM2 was critical for cell viability.This work demonstrates that SNPs in TRPM2 are associated with differences in gene expression, suggesting that modulation of expression of this innate immune gene contributes to susceptibility to R. equi pneumonia.
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Project description:Genome-wide association studies (GWAS) have identified approximately 50 loci associated with colorectal cancer (CRC) risk. However, the target genes and underlying mechanisms are largely unknown. We conducted a cis-expression quantitative trait loci (cis-eQTL) analysis using data from the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and the Colonomics projects. We identified 24 putative target genes for 17 index SNPs at Benjamini-Hochberg adjusted P < 0.05 in at least one of the datasets. By analyzing functional genomic data, our result further indicated that 18 genes (75%) showed evidence of cis-regulation by putative functional SNPs via promoter or enhancer-promoter interactions. We next performed in vitro functional assays for three genes, TMBIM1, AAMP, and CABLES2, and confirmed that they play a vital role in colorectal carcinogenesis via disruption of cell behavior. Furthermore, our results indicate that silencing CABLES2 can promote the PI3K/AKT pathway. Our study reveals new candidate susceptibility genes and provides novel insight into the biological mechanisms for CRC development.
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Project description:To identify SNPs predisposing to systemic mastocytosis (SM) we performed a two stage GWAs consisting of two cohorts from the UK and Germany at stage 1 and three cohorts from Spain, Italy and Denmark at stage 2. At both stages, the SM cases were compared with publicly available controls. The control cohorts used were WTCCC and KORA at stage 1 and the Spanish National DNA bank, InChianti and Inter99 at stage 2. The data available are raw intensity files for 480 SM cases that were genotyped at stage 1. Please see our publication (Galata et al 2020) for details regarding QC of the stage 1 samples.
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