ABSTRACT: Efforts to improve resilience in livestock production systems have focused on two objectives: investigating the genetic control of immune function as it pertains to robustness and disease resistance, and finding predictive markers for use in breeding programs. In this context, the peripheral blood transcriptome represents an important source of biological information about an individual's health and immunological status, and has been proposed for use as an intermediate phenotype to measure immune capacity. The objective of this work was to study the genetic architecture of variation in gene expression in the blood of healthy pigs using two approaches: an expression genome-wide association study (eGWAS) and allele-specific expression (ASE) analysis. The blood transcriptomes of 60-day-old Large White pigs were characterized by expression microarrays for eGWAS (243 animals) and by RNA-Seq for ASE analysis (38 animals). Using eGWAS, the expression levels of 1,901 genes were found to be associated with expression quantitative trait loci (eQTLs). We recovered 2,839 local and 1,752 distant associations (defined as single-nucleotide polymorphism, or SNP, located less or more than 1 Mb from expression probe, respectively). ASE analyses confirmed the extensive cis-regulation of gene transcription in blood, and revealed allelic imbalance in 2,286 SNPs, which affected 763 genes. eQTLs and ASE-genes were widely distributed on all chromosomes. By analyzing mutually overlapping eGWAS results, we were able to describe putative regulatory networks, which were further refined using ASE data. At the functional level, genes with genetically controlled expression that were detected by eGWAS and/or ASE analyses were significantly involved in biological processes related to RNA processing and immune function. In particular, numerous distant and local regulatory relationships were detected within the major histocompatibility complex region on chromosome 7, revealing ASE for most class I and II genes. This study represents, to the best of our knowledge, the first genome-wide map of the genetic control of gene expression in porcine peripheral blood. These results represent an important resource for the identification of genetic markers and blood biomarkers associated with variations in immunity traits in pigs, as well as any other complex traits for which blood is an appropriate surrogate tissue.
