title: Identification of a putative quantitative trait nucleotide in guanylate binding protein 5 for host response to PRRS virus infection.
abstract: BACKGROUND
  Previously, we identified a major quantitative trait locus (QTL) for host response to Porcine Respiratory and Reproductive Syndrome virus (PRRSV) infection in high linkage disequilibrium (LD) with SNP rs80800372 on Sus scrofa chromosome 4 (SSC4).
  
  
  RESULTS
  Within this QTL, guanylate binding protein 5 (GBP5) was differentially expressed (DE) (p < 0.05) in blood from AA versus AB rs80800372 genotyped pigs at 7,11, and 14 days post PRRSV infection. All variants within the GBP5 transcript in LD with rs80800372 exhibited allele specific expression (ASE) in AB individuals (p < 0.0001). A transcript re-assembly revealed three alternatively spliced transcripts for GBP5. An intronic SNP in GBP5, rs340943904, introduces a splice acceptor site that inserts five nucleotides into the transcript. Individuals homozygous for the unfavorable AA genotype predominantly produced this transcript, with a shifted reading frame and early stop codon that truncates the 88 C-terminal amino acids of the protein. RNA-seq analysis confirmed this SNP was associated with differential splicing by QTL genotype (p < 0.0001) and this was validated by quantitative capillary electrophoresis (p < 0.0001). The wild-type transcript was expressed at a higher level in AB versus AA individuals, whereas the five-nucleotide insertion transcript was the dominant form in AA individuals. Splicing and ASE results are consistent with the observed dominant nature of the favorable QTL allele. The rs340943904 SNP was also 100 % concordant with rs80800372 in a validation population that possessed an alternate form of the favorable B QTL haplotype.
  
  
  CONCLUSIONS
  GBP5 is known to play a role in inflammasome assembly during immune response. However, the role of GBP5 host genetic variation in viral immunity is novel. These findings demonstrate that rs340943904 is a strong candidate causal mutation for the SSC4 QTL that controls variation in host response to PRRSV.
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. jekoltes@iastate.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Koltes
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. ercfrtz@iastate.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Fritz-Waters
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. ceisley@iastate.edu.|Department of Statistics, Iowa State University, 1121 Snedecor Hall, Ames, IA, 50011, USA. ceisley@iastate.edu.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Eisley
authors.affiliation: USDA-ARS, BARC, APDL, Building1040, Beltsville, MD, 20705, USA. Igseo.Choi@ARS.USDA.GOV.
authors.forename: Igseo
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. bao1@ualberta.ca.
authors.forename: Hua
authors.initials: H
authors.lastname: Bao
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. kommadat@ualberta.ca.
authors.forename: Arun
authors.initials: A
authors.lastname: Kommadath
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. serao@iastate.edu.
authors.forename: Nick V L
authors.initials: NV
authors.lastname: Serão
authors.affiliation: Genesus Inc, 101 2nd Street, Oakville, MB, R0H 0Y0, Canada. nboddicker@genesus.com.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Boddicker
authors.affiliation: USDA-ARS, BARC, APDL, Building1040, Beltsville, MD, 20705, USA. Sam.Abrams@ars.usda.gov.
authors.forename: Sam M
authors.initials: SM
authors.lastname: Abrams
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. schroyen@iastate.edu.
authors.forename: Martine
authors.initials: M
authors.lastname: Schroyen
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. heri1008@iastate.edu.
authors.forename: Hyelee
authors.initials: H
authors.lastname: Loyd
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. cktuggle@iastate.edu.
authors.forename: Chris K
authors.initials: CK
authors.lastname: Tuggle
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. plastow@ualberta.ca.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Plastow
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. lguan@ualberta.ca.
authors.forename: Leluo
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. stothard@ualberta.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Stothard
authors.affiliation: USDA-ARS, BARC, APDL, Building1040, Beltsville, MD, 20705, USA. Joan.Lunney@ARS.USDA.GOV.
authors.forename: Joan K
authors.initials: JK
authors.lastname: Lunney
authors.affiliation: Department of Statistics, Iowa State University, 1121 Snedecor Hall, Ames, IA, 50011, USA. pliu@iastate.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. scarp@iastate.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: College of Veterinary Medicine, Kansas State University, K-231 Mosier Hall, Manhattan, KS, 66506, USA. browland@vet.k-state.edu.
authors.forename: Robert R R
authors.initials: RR
authors.lastname: Rowland
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. jdekkers@iastate.edu.
authors.forename: Jack C M
authors.initials: JC
authors.lastname: Dekkers
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. jreecy@iastate.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Reecy
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D019204:GTP-Binding Proteins / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation; D005838:Genotype; D020641:Polymorphism, Single Nucleotide; D019318:Porcine Reproductive and Respiratory Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000737:chemistry* / Q000276:immunology; D040641:Quantitative Trait Loci; D022821:RNA Splice Sites; D034421:Sus scrofa; D013552:Swine
chemical_list: D022821:RNA Splice Sites; D019204:GTP-Binding Proteins