Characterizing differential individual response to porcine reproductive and respiratory syndrome virus infection through statistical and functional analysis of gene expression

Maria E. Arceo, Catherine W. Ernst, Joan K. Lunney, Igseo Choi, Nancy E. Raney, Tinghua Huang, Christopher K. Tuggle, R. R.R. Rowland, Juan P. Steibel

Research output: Contribution to journalArticle

Abstract

We evaluated differences in gene expression in pigs from the Porcine Reproductive and Respiratory Syndrome (PRRS) Host Genetics Consortium initiative showing a range of responses to PRRS virus infection. Pigs were allocated into four phenotypic groups according to their serum viral level and weight gain. RNA obtained from blood at 0, 4, 7, 11, 14, 28, and 42 days post-infection (DPI) was hybridized to the 70-mer20K Pigoligoarray. We used a blocked reference design for the microarray experiment. This allowed us to account for individual biological variation in gene expression, and to assess baseline effects before infection (0DPI). Additionally, this design has the flexibility of incorporating future data for differential expression analysis. We focused on evaluating transcripts showing significant interaction of weight gain and serum viral level. We identified 491 significant comparisons [false discovery rate (FDR) = 10%] across all DPI and phenotypic groups. We corroborated the overall trend in direction and level of expression (measured as fold change) at 4 DPI using qPCR (r = 0.91, p < 0.0007). At 4 and 7 DPI, network and functional analyses were performed to assess if immune related gene sets were enriched for genes differentially expressed (DE) across four phenotypic groups. We identified cell death function as being significantly associated (FDR ≤ 5%) with several networks enriched for DE transcripts. We found the genes interferon-alpha 1 (IFNA1), major histocompatibility complex, class II, DQ alpha 1 (SLA-DQA1), and major histocompatibility complex, class II, DR alpha (SLA-DRA) to be DE (p ≤ 0.05) between phenotypic groups. Finally, we performed a power analysis to estimate sample size and sampling time-points for future experiments. We concluded the best scenario for investigation of early response to PRRSV infection consists of sampling at 0, 4, and 7 DPI using about 30 pigs per phenotypic group.

Original languageEnglish (US)
Article numberArticle 321
JournalFrontiers in Genetics
Volume3
Issue numberJAN
DOIs
StatePublished - Apr 19 2013
Externally publishedYes

Keywords

  • Functional analysis
  • Microarray
  • Porcine reproductive and respiratory syndrome
  • Power analysis
  • Quantitative PCR

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

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