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Integrative Analysis of Metabolomic, Proteomic and Genomic Data to Reveal Functional Pathways and Candidate Genes for Drip Loss in Pigs

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ABSTRACT

The aim of this study was to integrate multi omics data to characterize underlying functional pathways and candidate genes for drip loss in pigs. The consideration of different omics levels allows elucidating the black box of phenotype expression. Metabolite and protein profiling was applied in Musculus longissimus dorsi samples of 97 Duroc × Pietrain pigs. In total, 126 and 35 annotated metabolites and proteins were quantified, respectively. In addition, all animals were genotyped with the porcine 60 k Illumina beadchip. An enrichment analysis resulted in 10 pathways, amongst others, sphingolipid metabolism and glycolysis/gluconeogenesis, with significant influence on drip loss. Drip loss and 22 metabolic components were analyzed as intermediate phenotypes within a genome-wide association study (GWAS). We detected significantly associated genetic markers and candidate genes for drip loss and for most of the metabolic components. On chromosome 18, a region with promising candidate genes was identified based on SNPs associated with drip loss, the protein “phosphoglycerate mutase 2” and the metabolite glycine. We hypothesize that association studies based on intermediate phenotypes are able to provide comprehensive insights in the genetic variation of genes directly involved in the metabolism of performance traits. In this way, the analyses contribute to identify reliable candidate genes.

No MeSH data available.


Region on Sus scrofa chromosome (SSC) 18 with potential candidate genes for drip loss and associated metabolic traits phosphoglycerate mutase 2 and glycine. Drip loss measured in Musculus longissimus dorsi (LD) 24 h post-mortem (p.m.); PGAM2 = phosphoglycerate mutase 2; fat solid arrows = direct relation between SNPs and drip loss; thin solid arrows = indirect relation between SNPs and drip loss via metabolite glycine; dotted arrow = indirect relation between SNPs and drip loss via protein PGAM2; genes in boxes: CREB3L2 = cAMP responsive element binding protein 3 like 2; PTN = Sus scrofa pleiotropic factor beta; LRGUK = leucine-rich repeats and guanylate kinase domain containing; EXOC4 = exocyst complex component 4.
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ijms-17-01426-f003: Region on Sus scrofa chromosome (SSC) 18 with potential candidate genes for drip loss and associated metabolic traits phosphoglycerate mutase 2 and glycine. Drip loss measured in Musculus longissimus dorsi (LD) 24 h post-mortem (p.m.); PGAM2 = phosphoglycerate mutase 2; fat solid arrows = direct relation between SNPs and drip loss; thin solid arrows = indirect relation between SNPs and drip loss via metabolite glycine; dotted arrow = indirect relation between SNPs and drip loss via protein PGAM2; genes in boxes: CREB3L2 = cAMP responsive element binding protein 3 like 2; PTN = Sus scrofa pleiotropic factor beta; LRGUK = leucine-rich repeats and guanylate kinase domain containing; EXOC4 = exocyst complex component 4.

Mentions: The performed GWAS procedures resulted in a varying number of significant SNPs for drip, 11 metabolites and three proteins. The total of 871 significant SNPs are spread across the entire porcine genome, but concentrated on SSC 14, 17 and 18. For drip loss itself, promising candidate genes are located on SSC 18. This region has been earlier described by Jennen et al. [58] and Liu et al. [11]. In the region around 12 Mb, the meaning of “Sus scrofa pleiotropic factor beta” (PTN) (q ≤ 6.26 × 10−2) is highlighted by the direct neighborhood of gene “cAMP responsive element binding protein” (CREB3L2). CREB3L2 was identified by the GWAS of the protein PGAM2, which revealed an intronic SNP (ALGA0107449) as one of the most significant marker (Table 5). The family of cAMP response element binding proteins is crucial for a variety of cellular processes including cell proliferation, differentiation, apoptosis, extra-stimuli and stress response [59]. Although the meaning of CREB3L2 so far was not precisely described for meat quality, our results suggest that this gene seems to have a relevant influence in energy metabolism in skeletal muscle that is indicated by its interacting effect on PGAM2, glycine and drip loss (Figure 3).


Integrative Analysis of Metabolomic, Proteomic and Genomic Data to Reveal Functional Pathways and Candidate Genes for Drip Loss in Pigs
Region on Sus scrofa chromosome (SSC) 18 with potential candidate genes for drip loss and associated metabolic traits phosphoglycerate mutase 2 and glycine. Drip loss measured in Musculus longissimus dorsi (LD) 24 h post-mortem (p.m.); PGAM2 = phosphoglycerate mutase 2; fat solid arrows = direct relation between SNPs and drip loss; thin solid arrows = indirect relation between SNPs and drip loss via metabolite glycine; dotted arrow = indirect relation between SNPs and drip loss via protein PGAM2; genes in boxes: CREB3L2 = cAMP responsive element binding protein 3 like 2; PTN = Sus scrofa pleiotropic factor beta; LRGUK = leucine-rich repeats and guanylate kinase domain containing; EXOC4 = exocyst complex component 4.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037705&req=5

ijms-17-01426-f003: Region on Sus scrofa chromosome (SSC) 18 with potential candidate genes for drip loss and associated metabolic traits phosphoglycerate mutase 2 and glycine. Drip loss measured in Musculus longissimus dorsi (LD) 24 h post-mortem (p.m.); PGAM2 = phosphoglycerate mutase 2; fat solid arrows = direct relation between SNPs and drip loss; thin solid arrows = indirect relation between SNPs and drip loss via metabolite glycine; dotted arrow = indirect relation between SNPs and drip loss via protein PGAM2; genes in boxes: CREB3L2 = cAMP responsive element binding protein 3 like 2; PTN = Sus scrofa pleiotropic factor beta; LRGUK = leucine-rich repeats and guanylate kinase domain containing; EXOC4 = exocyst complex component 4.
Mentions: The performed GWAS procedures resulted in a varying number of significant SNPs for drip, 11 metabolites and three proteins. The total of 871 significant SNPs are spread across the entire porcine genome, but concentrated on SSC 14, 17 and 18. For drip loss itself, promising candidate genes are located on SSC 18. This region has been earlier described by Jennen et al. [58] and Liu et al. [11]. In the region around 12 Mb, the meaning of “Sus scrofa pleiotropic factor beta” (PTN) (q ≤ 6.26 × 10−2) is highlighted by the direct neighborhood of gene “cAMP responsive element binding protein” (CREB3L2). CREB3L2 was identified by the GWAS of the protein PGAM2, which revealed an intronic SNP (ALGA0107449) as one of the most significant marker (Table 5). The family of cAMP response element binding proteins is crucial for a variety of cellular processes including cell proliferation, differentiation, apoptosis, extra-stimuli and stress response [59]. Although the meaning of CREB3L2 so far was not precisely described for meat quality, our results suggest that this gene seems to have a relevant influence in energy metabolism in skeletal muscle that is indicated by its interacting effect on PGAM2, glycine and drip loss (Figure 3).

View Article: PubMed Central - PubMed

ABSTRACT

The aim of this study was to integrate multi omics data to characterize underlying functional pathways and candidate genes for drip loss in pigs. The consideration of different omics levels allows elucidating the black box of phenotype expression. Metabolite and protein profiling was applied in Musculus longissimus dorsi samples of 97 Duroc × Pietrain pigs. In total, 126 and 35 annotated metabolites and proteins were quantified, respectively. In addition, all animals were genotyped with the porcine 60 k Illumina beadchip. An enrichment analysis resulted in 10 pathways, amongst others, sphingolipid metabolism and glycolysis/gluconeogenesis, with significant influence on drip loss. Drip loss and 22 metabolic components were analyzed as intermediate phenotypes within a genome-wide association study (GWAS). We detected significantly associated genetic markers and candidate genes for drip loss and for most of the metabolic components. On chromosome 18, a region with promising candidate genes was identified based on SNPs associated with drip loss, the protein “phosphoglycerate mutase 2” and the metabolite glycine. We hypothesize that association studies based on intermediate phenotypes are able to provide comprehensive insights in the genetic variation of genes directly involved in the metabolism of performance traits. In this way, the analyses contribute to identify reliable candidate genes.

No MeSH data available.