Identification of genomic regions, genetic variants and gene networks regulating candidate genes for lipid metabolism in pig muscle.

The intramuscular fat content and fatty acid composition of porcine meat have a significant impact on its quality and nutritional value. This research aimed to investigate the expression of 45 genes involved in lipid metabolism in the longissimus dorsi muscle of three experimental pig backcrosses, with a 25% of Iberian background. To achieve this objective, we conducted an expression Genome-Wide Association Study (eGWAS) using gene expression levels in muscle measured by high-throughput real-time qPCR for 45 target genes and genotypes from the PorcineSNP60 BeadChip or Axiom Porcine Genotyping Array and 65 single nucleotide polymorphisms (SNPs) located in 20 genes genotyped by a custom-designed Taqman OpenArray in a cohort of 354 animals. The eGWAS analysis identified 301 eSNPs associated with 18 candidate genes (ANK2, APOE, ARNT, CIITA, CPT1A, EGF, ELOVL6, ELOVL7, FADS3, FASN, GPAT3, NR1D2, NR1H2, PLIN1, PPAP2A, RORA, RXRA and UCP3). Three cis-eQTL (expression quantitative trait loci) were identified for GPAT3, RXRA, and UCP3 genes, which indicates that a genetic polymorphism proximal to the same gene is affecting its expression. Furthermore, 24 trans-eQTLs were detected, and eight candidate regulatory genes were located in these genomic regions. Additionally, two trans-regulatory hotspots in Sus scrofa chromosomes 13 and 15 were identified. Moreover, a co-expression analysis performed on 89 candidate genes and the fatty acid composition revealed the regulatory role of four genes (FABP5, PPARG, SCD, and SREBF1). These genes modulate the levels of α-linolenic, arachidonic, and oleic acids, as well as regulating the expression of other candidate genes associated with lipid metabolism. The findings of this study offer novel insights into the functional regulatory mechanism of genes involved in lipid metabolism, thereby enhancing our understanding of this complex biological process.