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

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.

SUBMITTER: Puig-Oliveras A

PROVIDER: S-EPMC4989154 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Puig-Oliveras Anna A Revilla Manuel M Castelló Anna A Fernández Ana I AI Folch Josep M JM Ballester Maria M

Scientific reports 20160818

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, ...[more]

PMID: 27666082

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Project description:BACKGROUND: Porcine fatty acid composition is a key factor for quality and nutritive value of pork. Several QTLs for fatty acid composition have been reported in diverse fat tissues. The results obtained so far seem to point out different genetic control of fatty acid composition conditional on the fat deposits. Those studies have been conducted using simple approaches and most of them focused on one single tissue. The first objective of the present study was to identify tissue-specific and tissue-consistent QTLs for fatty acid composition in backfat and intramuscular fat, combining linkage mapping and GWAS approaches and conducted under single and multitrait models. A second aim was to identify powerful candidate genes for these tissue-consistent QTLs, using microarray gene expression data and following a targeted genetical genomics approach. RESULTS: The single model analyses, linkage and GWAS, revealed over 30 and 20 chromosomal regions, 24 of them identified here for the first time, specifically associated to the content of diverse fatty acids in BF and IMF, respectively. The analyses with multitrait models allowed identifying for the first time with a formal statistical approach seven different regions with pleiotropic effects on particular fatty acids in both fat deposits. The most relevant were found on SSC8 for C16:0 and C16:1(n-7) fatty acids, detected by both linkage and GWAS approaches. Other detected pleiotropic regions included one on SSC1 for C16:0, two on SSC4 for C16:0 and C18:2, one on SSC11 for C20:3 and the last one on SSC17 for C16:0. Finally, a targeted eQTL scan focused on regions showing tissue-consistent effects was conducted with Longissimus and fat gene expression data. Some powerful candidate genes and regions were identified such as the PBX1, RGS4, TRIB3 and a transcription regulatory element close to ELOVL6 gene to be further studied. CONCLUSIONS: Complementary genome scans have confirmed several chromosome regions previously associated to fatty acid composition in backfat and intramuscular fat, but even more, to identify new ones. Although most of the detected regions were tissue-specific, supporting the hypothesis that the major part of genes affecting fatty acid composition differs among tissues, seven chromosomal regions showed tissue-consistent effects. Additional gene expression analyses have revealed powerful target regions to carry the mutation responsible for the pleiotropic effects.

Project description:BackgroundFatty acids (FA) play a critical role in energy homeostasis and metabolic diseases; in the context of livestock species, their profile also impacts on meat quality for healthy human consumption. Molecular pathways controlling lipid metabolism are highly interconnected and are not fully understood. Elucidating these molecular processes will aid technological development towards improvement of pork meat quality and increased knowledge of FA metabolism, underpinning metabolic diseases in humans.ResultsThe results from genome-wide association studies (GWAS) across 15 phenotypes were subjected to an Association Weight Matrix (AWM) approach to predict a network of 1,096 genes related to intramuscular FA composition in pigs. To identify the key regulators of FA metabolism, we focused on the minimal set of transcription factors (TF) that the explored the majority of the network topology. Pathway and network analyses pointed towards a trio of TF as key regulators of FA metabolism: NCOA2, FHL2 and EP300. Promoter sequence analyses confirmed that these TF have binding sites for some well-know regulators of lipid and carbohydrate metabolism. For the first time in a non-model species, some of the co-associations observed at the genetic level were validated through co-expression at the transcriptomic level based on real-time PCR of 40 genes in adipose tissue, and a further 55 genes in liver. In particular, liver expression of NCOA2 and EP300 differed between pig breeds (Iberian and Landrace) extreme in terms of fat deposition. Highly clustered co-expression networks in both liver and adipose tissues were observed. EP300 and NCOA2 showed centrality parameters above average in the both networks. Over all genes, co-expression analyses confirmed 28.9% of the AWM predicted gene-gene interactions in liver and 33.0% in adipose tissue. The magnitude of this validation varied across genes, with up to 60.8% of the connections of NCOA2 in adipose tissue being validated via co-expression.ConclusionsOur results recapitulate the known transcriptional regulation of FA metabolism, predict gene interactions that can be experimentally validated, and suggest that genetic variants mapped to EP300, FHL2, and NCOA2 modulate lipid metabolism and control energy homeostasis in pigs.

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

Publications

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

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