Deciphering the genetic regulation of peripheral blood transcriptome in pigs through expression genome-wide association study and allele-specific expression analysis

Abstract

BackgroundEfforts to improve sustainability 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 young pigs using two approaches: an expression genome-wide association study (eGWAS) and allele-specific expression (ASE) analysis.ResultsThe blood transcriptomes of 60-day-old Large White pigs were analyzed by expression microarrays for eGWAS (242 animals) and by RNA-Seq for ASE analysis (38 animals). Using eGWAS, the expression levels of 1901 genes were found to be associated with expression quantitative trait loci (eQTLs). We recovered 2839 local and 1752 distant associations (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 2286 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 enriched in biological processes related to RNA processing and immune function. Indeed, 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.ConclusionsThis 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 interesting 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.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4354-6) contains supplementary material, which is available to authorized users.

Harnessing genomic information for livestock improvement

“…In cattle, such data sets have been generated for mammary gland, liver, blood and adrenal gland and have been used to identify causative genes underlying GWAS-identified QTL [41][42][43][44][45] . In pigs, eQTL studies have been conducted in skeletal muscle, lung, adipose tissue and liver [46][47][48][49][50][51][52][53][54][55][56][57] . In poultry, genome-wide eQTL analyses have been reported for liver, bone, adrenal gland and hypothalamus [58][59][60][61] .…”

Peer Review #2 of "Genomic analyses provide insights into breed-of-origin effects from purebreds on three-way crossbred pigs (v0.2)"

“…In total, we identified 251 ASE genes across adipose, heart, liver and skeletal muscle. To further explore the characteristics of these ASE genes, we made a comparison with ASE genes reported in previous studies for pigs (Esteve-Codina et al, 2011;Maroilley et al, 2017;Oczkowicz et al, 2018). We found none of the ASE genes was shared across the four datasets, suggesting that ASE gene may be tissuespecific or breed-specific ( Supplementary Figure S8).…”

“…Though previous studies have focused on ASE genes to investigate the breed-of-origin effects from purebreds on crossbred individuals for bacterial resistance (Wu et al, 2015), peripheral blood (Maroilley et al, 2017), brain development (Oczkowicz et al, 2018), prenatal skeletal muscle development (Yang et al, 2018), adipogenesis and lipid metabolism (Stachowiak et al, 2018), such studies are absent for DLY three-way crossbred pigs. Here, we first estimated the distribution of heterozygous SNPs in three kinds of three-way crossbred pigs via whole genome sequencing data originated from three purebreds (including 11 Duroc, 9 Landrace and 10 Yorkshire pigs).…”

Allele-specific expression reveals the phenotypic differences between thin- and fat-tailed sheep

“…The great variations in different phenotypic traits of two selected sheep breeds provide an opportunity for studying molecular mechanisms underlying gene expression related to phenotypic difference between thin-and fat-tailed sheep breeds. In this study, the candidate causative genes were detected by ASE analysis, which avoid the effect of trans-acting and has become research focus in recent years [24][25][26][27][28]. We divided all sheep individuals into 15 family trios.…”

“…Recently, high-throughput sequencing technologies allowed us to identify ASE genes at a transcriptome-wide level. Several studies in different species such as mouse [24], pig [25], cow [26], goat [27], sheep [28], mule [29] and dzo [29] have shown that the different expression levels of alleles due to ASE may lead to variation in phenotypes.…”