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Pathway deregulation and expression QTLs in response to Actinobacillus pleuropneumoniae infection in swine

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Abstract

Actinobacillus (A.) pleuropneumoniae is among the most important pathogens in pig. The agent causes severe economic losses due to decreased performance, the occurrence of acute or chronic pleuropneumonia, and an increase in death incidence. Since therapeutics cannot be used in a sustainable manner, and vaccination is not always available, new prophylactic measures are urgently needed. Recent research has provided evidence for a genetic predisposition in susceptibility to A. pleuropneumoniae in a Hampshire × German Landrace F2 family with 170 animals. The aim of the present study is to characterize the expression response in this family in order to unravel resistance and susceptibility mechanisms and to prioritize candidate genes for future fine mapping approaches. F2 pigs differed distinctly in clinical, pathological, and microbiological parameters after challenge with A. pleuropneumoniae. We monitored genome-wide gene expression from the 50 most and 50 least susceptible F2 pigs and identified 171 genes differentially expressed between these extreme phenotypes. We combined expression QTL analyses with network analyses and functional characterization using gene set enrichment analysis and identified a functional hotspot on SSC13, including 55 eQTL. The integration of the different results provides a resource for candidate prioritization for fine mapping strategies, such as TF, TFRC, RUNX1, TCN1, HP, CD14, among others.

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Authors and Affiliations

  1. Department of Veterinary Clinical Sciences, Justus-Liebig-University, Frankfurter Strasse 112, 35392, Giessen, Germany

    Gerald Reiner, Natalie Bertsch & Hermann Willems

  2. Clinic of Swine and Small Ruminants, Forensic Medicine and Ambulatory Service, University of Veterinary Medicine, Bischofsholer Damm 15, 30173, Hannover, Germany

    Doris Hoeltig & Karl-Heinz Waldmann

  3. Department of Infectious Diseases, Institute for Microbiology, University of Veterinary Medicine Hannover Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany

    Martin Selke

  4. Department of Pediatrics, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Inga Probst & Burkhardt Tuemmler

  5. ATLAS Biolabs GmbH, Friedrichstraße 147, 10117, Berlin, Germany

    Mario Drungowski

  6. Alacris Theranostics GmbH, Fabeckstr. 60-62, 14195, Berlin, Germany

    Felix Dreher

  7. Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics Berlin, Ihnestr. 73, 14195, Berlin, Germany

    Ralf Herwig

  8. Innovative Veterinary Diagnostics LTD (IVD), Heisterbergallee 12, 30453, Hannover, Germany

    Gerald Friedrich Gerlach

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Suppl Fig. 1

Correlation of gene expression and severity of disease in the parental landrace strain. a IL10: Comparison of RT-PCR (red) and Affymetrix (green) expression profiles with the corresponding lung-scores. Bars show microarray expression fold-changes from 4 infected animals (disease scores = 5.7, 7.8, 11.9 and 12.2) and averaged expression from 4 uninfected animals (disease score = 0). b TLR4: Comparison of RT-PCR (red) and Affymetrix (green) expression profiles with the corresponding lung-scores (TIFF 508 kb)

Suppl Fig. 2

WGCNA results. a Based on the expression profiles across the 100 animals co-expression clusters were computed with the R implementation of the method which yielded 11 clusters of co-expressed genes (colored panel at the bottom). b Clusters (left colored panel) were correlated with phenotypic disease scores (range [−1,1]). Significance of the observation is shown for each cluster by correlation value and P value. Two large clusters of genes (brown 1,179 genes, and blue 2,617 genes) are particularly significantly correlated with the disease scores. Genes belonging to these clusters are shown in Suppl Table 5 (TIFF 3907 kb)

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Reiner, G., Dreher, F., Drungowski, M. et al. Pathway deregulation and expression QTLs in response to Actinobacillus pleuropneumoniae infection in swine. Mamm Genome 25, 600–617 (2014). https://doi.org/10.1007/s00335-014-9536-9

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