Expression-based GWAS identifies variants, gene interactions and key regulators affecting intramuscular fatty acid content and composition in porcine meat.

Anna Puig-Oliveras,Josep M Folch,Manuel Revilla,Ana I Fernández,Anna Castelló,Maria Ballester

doi:10.1038/srep31803

Abstract

The aim of this work is to better understand the genetic mechanisms determining two complex traits affecting porcine meat quality: intramuscular fat (IMF) content and its fatty acid (FA) composition. With this purpose, expression Genome-Wide Association Study (eGWAS) of 45 lipid-related genes associated with meat quality traits in swine muscle (Longissimus dorsi) of 114 Iberian × Landrace backcross animals was performed. The eGWAS identified 241 SNPs associated with 11 genes: ACSM5, CROT, FABP3, FOS, HIF1AN, IGF2, MGLL, NCOA1, PIK3R1, PLA2G12A and PPARA. Three expression Quantitative Trait Loci (eQTLs) for IGF2, ACSM5 and MGLL were identified, showing cis-acting effects, whereas 16 eQTLs had trans regulatory effects. A polymorphism in the ACSM5 promoter region associated with its expression was identified. In addition, strong candidate genes regulating ACSM5, FOS, PPARA, PIK3R1, PLA2G12A and HIF1AN gene expression were also seen. Notably, the analysis highlighted the NR3C1 transcription factor as a strong candidate gene involved in the regulation of the 45 genes analysed. Finally, the IGF2, MGLL, MC2R, ARHGAP6, and NR3C1 genes were identified as potential regulators co-localizing within QTLs for fatness and growth traits in the IBMAP population. The results obtained increase our knowledge in the functional regulatory mechanisms involved in these complex traits.

Highlights

The experimental IBMAP population[6], a cross between Iberian x Landrace pigs, which clearly differs in growth, carcass and meat quality, such as the intramuscular fat (IMF) content and fatty acid (FA) composition, was generated to obtain a population with large phenotypic differences, in which alleles from both parental breeds are segregating and can be tested
IBMAP population and showing a wide range of IMF content and FA composition values were used for RNA extraction and RT-qPCR to perform expression Genome-Wide Association Study (eGWAS) (Supplementary Table S1)
The hierarchical cluster analysis showed that genes mainly related to lipogenic pathways (DGAT2, PPARG, SCD, Monoglyceride Lipase (MGLL), NCOA1, NCOA2, NCOA6, PRKAA1, SP1, SREBF1) clustered together, whereas genes mainly related to lipolytic pathways (ATF3, CPT1B, Peroxisome Proliferator-Activated Receptor Alpha (PPARA), PPARD, PPARGC1A) joined together (Fig. 2)

Summary

Introduction

The experimental IBMAP population[6], a cross between Iberian x Landrace pigs, which clearly differs in growth, carcass and meat quality, such as the IMF content and FA composition, was generated to obtain a population with large phenotypic differences, in which alleles from both parental breeds are segregating and can be tested Strategies such as QTL and GWAS have been useful to highlight many genes, for instance determining intramuscular fatty acid (IMFA) composition in the IBMAP population[6,7,8,9,10,11,12,13]. The detection of expression Quantitative Trait Loci (eQTLs) has recently been proposed as a good strategy to deepen the study of the genetic architecture of complex traits[15]. With the objective to better understand the mechanisms affecting IMF content and FA composition, we performed expression Genome-Wide Association Study (eGWAS) of 45 strong candidate genes for these traits, identified in previous studies by our group[12,16,17,18], in 114 BC1_LD animals

Objectives

Methods

Results

Conclusion