title: TLR4 single nucleotide polymorphisms (SNPs) associated with Salmonella shedding in pigs.
abstract: Toll-like receptor 4 (TLR4) is a key factor in the innate immune recognition of lipopolysaccharide (LPS) from Gram-negative bacteria. Previous studies from our group identified differences in the expression profile of TLR4 and genes affected by the TLR4 signaling pathway among pigs that shed varying levels of Salmonella, a Gram-negative bacterium. Therefore, genetic variation in this gene may be involved with the host's immune response to bacterial infections. The current study screened for single nucleotide polymorphisms (SNPs) in the TLR4 gene and tested their association with Salmonella fecal shedding. Pigs (n = 117) were intranasally challenged at 7 weeks of age with 1 × 10(9) CFU of S. Typhimurium χ4232 and were classified as low or persistent Salmonella shedders based on the levels of Salmonella being excreted in fecal material. Salmonella fecal shedding was determined by quantitative bacteriology on days 2, 7, 14, and 20/21 post exposure, and the cumulative levels of Salmonella were calculated to identify the low (n = 20) and persistent (n = 20) Salmonella shedder pigs. From those 40 animals, the TLR4 region was sequenced, and 18 single nucleotide polymorphisms (SNPs) in TLR4 were identified. Twelve SNPs have been previously described and six are novel SNPs of which five are in the 5' untranslated region and one is in intron 2. Single marker association test identified 13 SNPs associated with the qualitative trait of Salmonella fecal shedding, and seven of those SNPs were also associated with a quantitative measurement of fecal shedding (P < 0.05). Using a stepwise regression process, a haplotype composed of SNPs rs80787918 and rs80907449 (P ≤ 4.0 × 10(-3)) spanning a region of 4.9 Kb was identified, thereby providing additional information of the influence of those SNPs on Salmonella fecal shedding in pigs.
authors.affiliation: USDA/ARS/National Animal Disease Center, 1920 Dayton Ave, Ames, IA, USA, jalusa.kich@embrapa.br.
authors.forename: Jalusa Deon
authors.initials: JD
authors.lastname: Kich
authors.forename: Jolita Janutenaite
authors.initials: JJ
authors.lastname: Uthe
authors.forename: Magda Vieira
authors.initials: MV
authors.lastname: Benavides
authors.forename: Maurício Egídio
authors.initials: ME
authors.lastname: Cantão
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zanella
authors.forename: Christopher Keith
authors.initials: CK
authors.lastname: Tuggle
authors.forename: Shawn Michelle Dunkin
authors.initials: SM
authors.lastname: Bearson
mesh_terms: D000818:Animals; D019540:Area Under Curve; D057138:Bacterial Shedding / Q000235:genetics*; D015169:Colony Count, Microbial; D006239:Haplotypes / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012475:Salmonella / Q000254:growth & development / Q000502:physiology*; D034421:Sus scrofa / Q000235:genetics* / Q000382:microbiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D051197:Toll-Like Receptor 4