Genetic markers for screening animals for improved disease resistance (NRAMP)

A method for determining improved innate immunity, disease resistance or performance in animals is disclosed. The method involves assays for a genetic differences in the NRAMP1 gene of the animal which is associated with superior disease resistance. Novel NRAMP1 sequence, assays, and compositions for identifying the presence of absence of these alleles are provided

Association of bacterial infection traits with genetic variation at candidate genes for porcine disease resistance

We predict that it may be possible to improve pig disease resistance to Salmonella infection by studying genes that control a piglet’s initial immune response. The NRAMP1 gene controls susceptibility to multiple pathogens and acts within the macrophage. The BPI gene encodes a neutrophil protein with inhibitory/killing functions against multiple gram-negative bacteria. We investigated NRAMP1 and BPI as candidate genes for contributing to resistance in Salmonella choleraesuis (SC) challenge in pigs. Five NRAMP1 sequence differences (polymorphisms, SNPs) were found, while we cloned and sequenced the full-length BPI gene and identified four polymorphisms at BPI. The effects these polymorphisms have on resistance to infection were tested in two experimental disease studies. In study 1, results showed NRAMP1 and BPI genotypes were associated with decreased fecal bacterial load during infection (P values: \u3c .0006 to \u3c .06). Immune cell numbers were also associated with BPI genotypes. In the second study, many additional immune traits and spleen and liver bacterial counts were collected. The NRAMP1 genotypes were associated with bacterial count in liver (P \u3c .05 and P \u3c .0006) and with polymorphonuclear phagocytes (P values from \u3c .003 to \u3c .05). The BPI genotypes were significantly associated with bacteria uptake by immune cells and with bacterial counts in liver (P\u3c.1) and lymphocyte response post-challenge (P\u3c.0001). These data indicate NRAMP1 and/or BPI gene variation may control, in part, response to Salmonella infection in pigs, and that these differences could be used to identify resistant animals

Species-Specific Variation in RELA Underlies Differences in NF-κB Activity: a Potential Role in African Swine Fever Pathogenesis▿

African swine fever virus (ASFV) is a highly infectious disease of domestic pigs, with virulent isolates causing a rapidly fatal hemorrhagic fever. In contrast, the porcine species endogenous to Africa tolerate infection. The ability of the virus to persist in one host while killing another genetically related host implies that disease severity may be, in part, modulated by host genetic variation. To complement transcription profiling approaches to identify the underlying genetic variation in the host response to ASFV, we have taken a candidate gene approach based on known signaling pathways that interact with the virus-encoded immunomodulatory protein A238L. We report the sequencing of these genes from different pig species and the identification and initial in vitro characterization of polymorphic variation in RELA (p65; v-rel reticuloendotheliosis viral oncogene homolog A), the major component of the NF-κB transcription factor. Warthog RELA and domestic pig RELA differ at three amino acids. Transient cell transfection assays indicate that this variation is reflected in reduced NF-κB activity in vitro for warthog RELA but not for domestic pig RELA. Induction assays indicate that warthog RELA and domestic pig RELA are elevated essentially to the same extent. Finally, mutational studies indicate that the S531P site conveys the majority of the functional variation between warthog RELA and domestic pig RELA. We propose that the variation in RELA identified between the warthog and domestic pig has the potential to underlie the difference between tolerance and rapid death upon ASFV infection

Differences in susceptibility to Haemophilus parasuis infection in pigs

In animal breeding programs, deoxyribonucleic acid (DNA) markers can be used to identify sires that are less susceptible to disease. These DNA markers are typically discovered in populations that display differences in susceptibility. To find those differences, it was hypothesized that sires influence their offspring responses to infection with H. parasuis. To identify differences in susceptibility, colostrum-deprived pigs derived from 6 sires were inoculated with a virulent strain of H. parasuis serovar 5. Pigs were infected at 21-d of age and euthanized 1, 2, or 3 days post-infection. Rectal temperatures, bacterial detection, clinical signs, and lesions were measured by comparing disease susceptibility in the offspring from each sire. The effect of the sire on the severity of disease in the offspring was statistically analyzed using to a 2-way ANOVA with sire and test day as fixed effects. Significant differences among sires were found for lesions, rectal temperatures from days 0–1 and 0–2 (P < 0.05) and marginal effects for clinical signs (P = 0.08). On average, the offspring of sire H94 was the most susceptible to challenge. Responses to infection were categorized to determine the clinical responses and analyzed by Chi square. Overall, 10% of all pigs infected were fully resistant to H. parasuis infection. Boar H94 didn’t produce any fully resistant offspring. Differences in susceptibility to H. parasuis were observed, and the results support the hypothesis that sires influence their offspring’s response to infection. Tissues from this population could be used to identify DNA markers for genetic selection of sires that produce offspring more resistant to H. parasuis infection