Genetic architecture of gene expression underlying variation in host response to porcine reproductive and respiratory syndrome virus infection

It has been shown that inter-individual variation in host response to porcine reproductive and respiratory syndrome (PRRS) has a heritable component, yet little is known about the underlying genetic architecture of gene expression in response to PRRS virus (PRRSV) infection. Here, we integrated genome-wide genotype, gene expression, viremia level, and weight gain data to identify genetic polymorphisms that are associated with variation in inter-individual gene expression and response to PRRSV infection in pigs. RNA-seq analysis of peripheral blood samples collected just prior to experimental challenge (day 0) and at 4, 7, 11 and 14 days post infection from 44 pigs revealed 6,430 differentially expressed genes at one or more time points post infection compared to the day 0 baseline. We mapped genetic polymorphisms that were associated with inter-individual differences in expression at each day and found evidence of cis-acting expression quantitative trait loci (cis-eQTL) for 869 expressed genes (qval \u3c 0.05). Associations between cis-eQTL markers and host response phenotypes using 383 pigs suggest that host genotype-dependent differences in expression of GBP5, GBP6, CCHCR1 and CMPK2 affect viremia levels or weight gain in response to PRRSV infection

Analysis of Gene Expression in a Region Associated with Host Response to Porcine Reproductive and Respiratory Syndrome Virus Challenge

Previous work identified a 1 Megabasepair region encompassing a quantitative trait locus (QTL) on Sus scrofa chromosome 4 associated with response to PRRS virus infection, in terms of weight gain and PRRS viremia. To identify candidate genes in the region responsible for these effects, we evaluated the expression of genes in the region by RNAseq using RNA isolated from whole blood taken from 8 pairs of littermates at 5 time-points following experimental infection with the PRRS virus. Each littermate pair included one individual with the favorable genotype (AB) for the SSC4 region and one with the unfavorable genotype (AA). A comparison of the gene transcript counts between AB and AA individuals was performed with a statistical model that also used sequence information to identify transcripts with allele-specific expression (A versus B) in the AB individuals. These analyses revealed a few candidate genes, with one gene in particular being differentially expressed at multiple time-points and having a high level of overall gene expression. This candidate gene is promising for follow-up functional biology studies to validate and detail its role in host response to PRRS virus infection.</p

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Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa

Background: Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory ill

Genetic architecture of gene expression underlying variation in host response to porcine reproductive and respiratory syndrome virus infection

It has been shown that inter-individual variation in host response to porcine reproductive and respiratory syndrome (PRRS) has a heritable component, yet little is known about the underlying genetic architecture of gene expression in response to PRRS virus (PRRSV) infection. Here, we integrated genome-wide genotype, gene expression, viremia level, and weight gain data to identify genetic polymorphisms that are associated with variation in inter-individual gene expression and response to PRRSV infection in pigs. RNA-seq analysis of peripheral blood samples collected just prior to experimental challenge (day 0) and at 4, 7, 11 and 14 days post infection from 44 pigs revealed 6,430 differentially expressed genes at one or more time points post infection compared to the day 0 baseline. We mapped genetic polymorphisms that were associated with inter-individual differences in expression at each day and found evidence of cis-acting expression quantitative trait loci (cis-eQTL) for 869 expressed genes (qval cis-eQTL markers and host response phenotypes using 383 pigs suggest that host genotype-dependent differences in expression of GBP5, GBP6, CCHCR1 and CMPK2 affect viremia levels or weight gain in response to PRRSV infection.This article is published as Kommadath, Arun, Hua Bao, Igseo Choi, James M. Reecy, James E. Koltes, Elyn Fritz-Waters, Chris J. Eisley et al. "Genetic architecture of gene expression underlying variation in host response to porcine reproductive and respiratory syndrome virus infection." Scientific reports 7 (2017): 46203. doi: 10.1038/srep46203.</p