Document Type
Article
Publication Version
Published Version
Publication Date
2015
Journal or Book Title
BMC Genomics
Volume
16
First Page
1
Last Page
13
DOI
10.1186/s12864-015-1635-9
Abstract
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). 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. 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.
Rights
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
Language
en
File Format
application/pdf
Recommended Citation
Koltes, James Eugene; Fritz-Waters, Eric R.; Eisley, Christopher J.; Choi, Igseo; Bao, Hua; Kommadath, Arun; Serão, Nick V. L.; Boddicker, Nicholas James; Abrams, Samuel M.; Schroyen, Martine; Loyd, Hyelee Park; Tuggle, Christopher K.; Plastow, Graham S.; Guan, LeLuo; Stothard, Paul; Lunney, Joan K.; Liu, Peng; Carpenter, Susan; Rowland, Raymond; Dekkers, Jack C. M.; and Reecy, James M., "Identification of a Putative Quantitative Trait Nucleotide in Guanylate Binding Protein 5 for Host Response to PRRS Virus Infection" (2015). Animal Science Publications. 164.
https://lib.dr.iastate.edu/ans_pubs/164
Included in
Agriculture Commons, Animal Sciences Commons, Molecular Genetics Commons, Veterinary Infectious Diseases Commons
Comments
This article is from BMC Genomics 16 (2015): 412, doi:10.1186/s12864-015-1635-9.