Relationship of bovine &lt;i&gt;TNF-α&lt;/i&gt; gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle

Cheng, Yafen; Huang, Chenshen; Tsai, Hsiang‐Jung

doi:10.1292/jvms.15-0506

Cited by 17 publications

(6 citation statements)

References 37 publications

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“…The correlation between TNFα gene polymorphism and resistance/susceptibility to mastitis (Ranjan et al 2015), tuberculosis (Cheng et al 2016) and EBL has been investigated in a limited number of studies (Konnai et al 2006;Bojarojc-Nosowicz et al 2015;Lendez et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Relationship between polymorphism in the tumour necrosis factor-alpha gene and selected indices and cell subpopulations in naturally bovine leukaemia virus-infected and healthy cows

Bojarojć-Nosowicz¹,

Kaczmarczyk²,

Jastrzębska³

2018

Vet. Med. - Czech

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Section: Discussionmentioning

confidence: 99%

Relationship between polymorphism in the tumour necrosis factor-alpha gene and selected indices and cell subpopulations in naturally bovine leukaemia virus-infected and healthy cows

Bojarojć-Nosowicz¹,

Kaczmarczyk²,

Jastrzębska³

2018

Vet. Med. - Czech

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“…< 0.10 from 80 to 182 SNPs for the LIM breed. Inspection of Additional file 7 reveals notable gene loci associated with enriched GWAS SNPs for the HOF breed including the allograft inflammatory factor 1 gene ( AIF1 ), which encodes a protein that promotes macrophage activation and proinflammatory activity [ 63 ]; the ciliogenesis associated kinase 1 gene ( CILK1 aka ICK ); IL17A and IL7F , which encode proinflammatory cytokines and contain polymorphisms in the human orthologs that have been associated with lower human TB disease incidence [ 64 , 65 ]; the integrin subunit beta 3 gene ( ITGB3 ), which encodes a protein that has been shown to regulate matrix metalloproteinase secretion in pulmonary human TB [ 66 ]; the neuraminidase 1 gene ( NEU1 ), which encodes a protein that regulates phagocytosis in macrophages [ 67 ]; and the TNF gene that encodes TNF (aka TNF-α), a key cytokine for generation and maintenance of the granuloma, and where gene polymorphisms have been linked to resistance to M. bovis infection [ 68 ]. Gene loci associated with enriched GWAS SNPs for the CHA breed group also included the CILK1 gene (aka ICK ) and the Kelch repeat and BTB domain containing 3 gene ( KCNJ15 ), which has been detected as an expression biomarker for human TB [ 69 ]; the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 gene ( TCIRG1 ), a known antimycobacterial host defence gene that has been shown to be a key hub gene associated with IFN-γ stimulation of human macrophages [ 70 ]; and the Von Willebrand factor gene ( VWF ).…”

Section: Resultsmentioning

confidence: 99%

Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria

et al. 2021

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Background Bovine TB (bTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production. The key innate immune cell that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection. Results The host gene expression data consisted of RNA-seq data from bovine alveolar macrophages (bAM) infected with M. bovis at 24 and 48 h post-infection (hpi) compared to non-infected control bAM. These RNA-seq data were analysed using three distinct computational pipelines to produce six separate gene sets: 1) DE genes filtered using stringent fold-change and P-value thresholds (DEG-24: 378 genes, DEG-48: 390 genes); 2) genes obtained from expression correlation networks (CON-24: 460 genes, CON-48: 416 genes); and 3) genes obtained from differential expression networks (DEN-24: 339 genes, DEN-48: 495 genes). These six gene sets were integrated with three bTB breed GWAS data sets by employing a new genomics data integration tool—gwinteR. Using GWAS summary statistics, this methodology enabled detection of 36, 102 and 921 prioritised SNPs for Charolais, Limousin and Holstein-Friesian, respectively. Conclusions The results from the three parallel analyses showed that the three computational approaches could identify genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets. These analyses also demonstrated significant differences among breeds, with the Holstein-Friesian breed GWAS proving most useful for prioritising SNPS through data integration. Because the functional genomics data were generated using bAM from this population, this suggests that the genomic architecture of bTB resilience traits may be more breed-specific than previously assumed.

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“…For the CHA breed, SNP enrichment using gwinteR was only observed for the CON-24 input gene set for the genomic interval between ± 10 to 40 kb. gene loci associated with enriched GWAS SNPs for the HOFR breed including the allograft in ammatory factor 1 gene (AIF1), which encodes a protein that promotes macrophage activation and proin ammatory activity [61]; the ciliogenesis associated kinase 1 gene (CILK1 aka ICK); IL17A and IL7F, which encode proin ammatory cytokines and contain polymorphisms in the human orthologs that have been associated with lower human TB disease incidence [62,63]; the integrin subunit beta 3 gene (ITGB3), which encodes a protein that has been shown to regulate matrix metalloproteinase secretion in pulmonary human TB [64]; the neuraminidase 1 gene (NEU1), which encodes a protein that regulates phagocytosis in macrophages [65]; and the TNF gene that encodes TNF (aka TNFα), a key cytokine for generation and maintenance of the granuloma, and where gene polymorphisms have been linked to resistance to M. bovis infection [66]. Gene loci associated with enriched GWAS SNPs for the CHA breed group also included the CILK1 gene (aka ICK) and the Kelch repeat and BTB domain containing 3 gene (KCNJ15), which has been detected as an expression biomarker for human TB [67]; the T cell immune regulator 1, ATPase H + transporting V0 subunit a3 gene (TCIRG1), a known antimycobacterial host defence gene that has been shown to be a key hub gene associated with IFN-γ stimulation of human macrophages [68]; and the Von Willebrand factor gene (VWF).…”

Section: Gwas Integration and Identi Cation Of Additional Snp-trait Amentioning

confidence: 99%

Integrative Genomics of the Mammalian Alveolar Macrophage Response to Intracellular Mycobacteria

Hall

Mullen

McHugo

et al. 2020

Preprint

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BackgroundBovine TB (BTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production, particularly in many developing countries. The key innate immune that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection.ResultsThe host gene expression data consisted of bovine RNA-seq data from alveolar macrophages infected with M. bovis at 24 and 48 hours post-infection. These RNA-seq data were analysed using three distinct analysis pipelines and novel response pathways and modules were further refined using cross-comparison and integration of the results. First, a differential expression analysis was carried out to determine the most significantly differentially expressed (DE) genes between conditions at each time point. Second, two networks were constructed at each time point using gene correlation patterns to determine changes in expression across conditions. Functional sub-modules within each correlation network were selected by statistical criteria for modularity. Third, a base gene interaction network of the mammalian host response to mycobacterial infection was generated using the GeneCards database and InnateDB. Differential gene expression data were superimposed on this base network to extract functional modules of interconnected DE genes.ConclusionsBovine GWAS data was obtained from a published BTB susceptibility/resistance study. The results from the three parallel analyses were integrated with this data to determine which of the three approaches identified genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets.

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Relationship of bovine <i>TNF-α</i> gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle

Cited by 17 publications

References 37 publications

Relationship between polymorphism in the tumour necrosis factor-alpha gene and selected indices and cell subpopulations in naturally bovine leukaemia virus-infected and healthy cows

Relationship between polymorphism in the tumour necrosis factor-alpha gene and selected indices and cell subpopulations in naturally bovine leukaemia virus-infected and healthy cows

Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria

Integrative Genomics of the Mammalian Alveolar Macrophage Response to Intracellular Mycobacteria

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