TRPM2 SNP genotype previously associated with susceptibility to Rhodococcus equi pneumonia in Quarter Horse foals displays differential gene expression identified using RNA-Seq.
Abstract: 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.
Publication Date: 2016-12-05 PubMed ID: 27919223PubMed Central: PMC5139010DOI: 10.1186/s12864-016-3345-3Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research investigates how the genetic mutation within TRPM2, a gene found in Quarter Horse foals, affects susceptibility to a severe form of pneumonia caused by the bacterium Rhodococcus equi (R.equ). The study, involving analyzing RNA sequences of 12 horses, found differential gene expression tied to three different genetic forms of the mutation, suggesting the gene’s varying expression could influence disease susceptibility.
Introduction: The Role of TRPM2 and Rhodococcus equi Pneumonia
- The Rhodococcus equi bacterium primarily impacts young foals and immuno-compromised individuals, leading to severe pneumonia.
- Despite the bacteria’s impact, scientific understanding of the genetic mechanisms dictating susceptibility and resistance to R. equi is currently limited.
- Prior genome-wide association studies had pointed to a region on equine chromosome 26 linked to clinical pneumonia through Single-Nucleotide Polymorphism (SNP).
- This research aims to better understand this region and the functioning of the specific SNP located within the TRPM2 gene that’s associated with R. equi pneumonia.
Methodology: Genotyping and RNA-Seq Analysis
- The study utilized RNA-Sequencing (RNA-Seq) to analyze the genes of 12 horses representing the three different genotypic forms of the identified SNP.
- This provided a comprehensive profiling of gene expression that highlighted differentially expressed genes in horses with varying genotypic forms of the mutation.
Outcomes: Association of TRPM2 SNPs with Differential Gene Expression
- The study found a differential expression in genes related to innate immune response when comparing horses homozygous for the A allele with those of the AB and BB genotypic forms.
- Additionally, analysis of RNA-Seq data also indicated the existence of multiple transcripts and differential expression at the TRPM2 locus. This is consistent with earlier studies on human cell lines where TRPM2’s isoform-specific expression was critical for cell survival.
- Overall, the research provides an evidence of association between SNPs in TRPM2 and differences in gene expression. This suggests that the differential exposure to this gene may influence susceptibility to R. equi pneumonia in horses.
Cite This Article
APA
McQueen CM, Whitfield-Cargile CM, Konganti K, Blodgett GP, Dindot SV, Cohen ND.
(2016).
TRPM2 SNP genotype previously associated with susceptibility to Rhodococcus equi pneumonia in Quarter Horse foals displays differential gene expression identified using RNA-Seq.
BMC Genomics, 17(1), 993.
https://doi.org/10.1186/s12864-016-3345-3 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX, USA.
- Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- , 6666 Ranch, 1102 Dash For Cash Road, Guthrie, TX, USA.
- Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA. sdindot@cvm.tamu.edu.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA. ncohen@cvm.tamu.edu.
MeSH Terms
- Actinomycetales Infections / veterinary
- Animals
- Gene Expression
- Gene Expression Profiling
- Genetic Predisposition to Disease
- Genotype
- High-Throughput Nucleotide Sequencing
- Horse Diseases / etiology
- Horses
- Phenotype
- Polymorphism, Single Nucleotide
- Rhodococcus equi
- TRPM Cation Channels / genetics
- Transcriptome
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