Abstract
Feral swine (Sus scrofa) are a destructive invasive species widespread throughout the United States that disrupt ecosystems, damage crops, and carry pathogens of concern for the health of domestic stock and humans including Brucella suis—the causative organism for swine brucellosis. In domestic swine, brucellosis results in reproductive failure due to abortions and infertility. Contact with infected feral swine poses spillover risks to domestic pigs as well as humans, companion animals, wildlife, and other livestock. Genetic factors influence the outcome of infectious diseases; therefore, genome wide association studies (GWAS) of differential immune responses among feral swine can provide an understanding of disease dynamics and inform management to prevent the spillover of brucellosis from feral swine to domestic pigs. We sought to identify loci associated with differential antibody responses among feral swine naturally infected with B. suis using a case-control GWAS. Tissue, serum, and genotype data (68,516 bi-allelic single nucleotide polymorphisms) collected from 47 feral swine were analyzed in this study. The 47 feral swine were culture positive for Brucella spp. Of these 47, 16 were antibody positive (cases) whereas 31 were antibody negative (controls). Single-locus GWAS were performed using efficient mixed-model association eXpedited (EMMAX) methodology with three genetic models: additive, dominant, and recessive. Eight loci associated with seroconversion were identified on chromosome 4, 8, 9, 10, 12, and 18. Subsequent bioinformatic analyses revealed nine putative candidate genes related to immune function, most notably phagocytosis and induction of an inflammatory response. Identified loci and putative candidate genes may play an important role in host immune responses to B. suis infection, characterized by a detectable bacterial presence yet a differential antibody response. Given that antibody tests are used to evaluate brucellosis infection in domestic pigs and for disease surveillance in invasive feral swine, additional studies are needed to fully understand the genetic component of the response to B. suis infection and to more effectively translate estimates of Brucella spp. antibody prevalence among feral swine to disease control management action.
Highlights
In the United States (U.S.) there are ∼6 million invasive feral swine (Sus scrofa), which are defined as any released or escaped domestic pigs, Eurasian wild boars, or hybrids of the two [1, 2]
A thorough review of candidate gene function, infection kinetics, and the immunologic response to B. suis infection reduced the number of putative candidate genes from 40 to three:(1) acyloxyacyl hydrolase (AOAH), [2] engulfment and cell motility 1 (ELMO1), and [3] prostaglandin synthase 2 (PTGS2)
Locus rs339122633 was located within an intron of Hemicentin 1 (HMCN1); based on our current understanding of the functions of HMCN1, there is no obvious link to B. suis infection
Summary
In the United States (U.S.) there are ∼6 million invasive feral swine (Sus scrofa), which are defined as any released or escaped domestic pigs, Eurasian wild boars, or hybrids of the two [1, 2]. Both the abundance of feral swine and extent of the geographic range have increased rapidly over the past 30 years due to the high reproductive potential of the species, limited predation pressure, abundance of food (both native flora and fauna and agricultural products), and human-mediated introduction into uninvaded habitats [3, 4]. Among the broader costs associated with the expansion of this invasive species, feral swine serve as an important reservoir for a number of pathogens (e.g., Brucella spp., pseudorabies virus, and trichinella) with the potential for spillover to livestock, humans, companion animals, and wildlife [7,8,9]
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