Abstract
BackgroundThe complement system is an evolutionary ancient mechanism that plays an essential role in innate immunity and contributes to the acquired immune response. Three modes of activation, known as classical, alternative and lectin pathway, lead to the initiation of a common terminal lytic pathway. The terminal complement components (TCCs: C6, C7, C8A, C8B, and C9) are encoded by the genes C6, C7, C8A, C8B, C8G, and C9. We aimed at experimentally testing the porcine genes encoding TCCs as candidate genes for immune competence and disease resistance by addressing the three-way relationship of genotype, health related phenotype, and mRNA expression.ResultsComparative sequencing of cDNAs of animals of the breeds German Landrace, Piétrain, Hampshire, Duroc, Vietnamese Potbelly Pig, and Berlin Miniature Pig (BMP) revealed 30 SNPs (21 in protein domains, 12 with AA exchange). The promoter regions (each ~1.5 kb upstream the transcription start sites) of C6, C7, C8A, C8G, and C9 exhibited 29 SNPs. Significant effects of the TCC encoding genes on hemolytic complement activity were shown in a cross of Duroc and BMP after vaccination against Mycoplasma hyopneumoniae, Aujeszky disease virus and PRRSV by analysis of variance using repeated measures mixed models. Family based association tests (FBAT) confirmed the associations. The promoter SNPs were associated with the relative abundance of TCC transcripts obtained by real time RT-PCR of 311 liver samples of commercial slaughter pigs. Complement gene expression showed significant relationship with the prevalence of acute and chronic lung lesions.ConclusionsThe analyses point to considerable variation of the porcine TCC genes and promote the genes as candidate genes for disease resistance.
Highlights
The complement system is an evolutionary ancient mechanism that plays an essential role in innate immunity and contributes to the acquired immune response
The analyses point to considerable variation of the porcine terminal complement components (TCCs) genes and promote the genes as candidate genes for disease resistance
Due to the lack of trait records related to animal health from the field we proposed to evaluate transcript levels of immune genes including TCCs obtained at slaughter as biomarkers for disease resistance
Summary
The complement system is an evolutionary ancient mechanism that plays an essential role in innate immunity and contributes to the acquired immune response. Known as classical, alternative and lectin pathway, lead to the initiation of a common terminal lytic pathway. We aimed at experimentally testing the porcine genes encoding TCCs as candidate genes for immune competence and disease resistance by addressing the three-way relationship of genotype, health related phenotype, and mRNA expression. All the three pathways lead to the initiation of a common terminal lytic pathway and the formation of the membrane attack complex (MAC), which causes lysis of the invading pathogens/microbes and is an assembly of the homologous components C5b, C6, C7, C8, and C9. We aimed at structural and functional characterization of the porcine genes encoding TCCs and experimentally qualifying TCCs as candidate genes for immune competence and disease resistance by addressing the three-way relationship of genotype, health related phenotype, and mRNA expression
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