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Novel Genomic Regions Associated with Intramuscular Fatty Acid Composition in Rabbits.

ABSTRACT: Intramuscular fat (IMF) content and its composition affect the quality of meat. Selection for IMF generated a correlated response on its fatty acid composition. The increase of IMF content is associated with an increase of its saturated (SFA) and monounsaturated (MUFA) fatty acids, and consequently a decrease of polyunsaturated fatty acids (PUFA). We carried out a genome wide association study (GWAS) for IMF composition on two rabbit lines divergently selected for IMF content, using a Bayes B procedure. Association analyses were performed using 475 individuals and 90,235 Single Nucleotide Polymorphisms (SNPs). The main objectives were to identify genomic regions associated with the IMF composition and to generate a list of candidate genes. Genomic regions associated with the intramuscular fatty acid composition were spread across different rabbit chromosomes (OCU). An important region at 34.0-37.9 Mb on OCU1 was associated with C14:0, C16:0, SFA, and C18:2n6, explaining 3.5%, 11.2%, 11.3%, and 3.2% of the genomic variance, respectively. Another relevant genomic region was found to be associated at 46.0-48.9 Mb on OCU18, explaining up to 8% of the genomic variance of MUFA/SFA. The associated regions harbor several genes related to lipid metabolism, such as SCD, PLIN2, and ERLIN1. The main genomic regions associated with the fatty acids were not previously associated with IMF content in rabbits. Nonetheless, MTMR2 is the only gene that was associated with both the IMF content and composition in rabbits. Our study highlighted the polygenic nature of the fatty acids in rabbits and elucidated its genetic background.

SUBMITTER: Laghouaouta H

PROVIDER: S-EPMC7697864 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Novel Genomic Regions Associated with Intramuscular Fatty Acid Composition in Rabbits.

Laghouaouta Houda H Sosa-Madrid Bolívar Samuel BS Zubiri-Gaitán Agostina A Hernández Pilar P Blasco Agustín A

Animals : an open access journal from MDPI 20201111 11

Intramuscular fat (IMF) content and its composition affect the quality of meat. Selection for IMF generated a correlated response on its fatty acid composition. The increase of IMF content is associated with an increase of its saturated (SFA) and monounsaturated (MUFA) fatty acids, and consequently a decrease of polyunsaturated fatty acids (PUFA). We carried out a genome wide association study (GWAS) for IMF composition on two rabbit lines divergently selected for IMF content, using a Bayes B pr ...[more]

PMID: 33187110

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Project description:BACKGROUND: New advances in high-throughput technologies have allowed for the massive analysis of genomic data, providing new opportunities for the characterization of the transcriptome architectures. Recent studies in pigs have employed RNA-Seq to explore the transcriptome of different tissues in a reduced number of animals. The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-Seq. RESULTS: The liver transcriptomes of two female groups (H and L) with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L) and 270 (H) lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96), as well as between microarrays and RNA-Seq (r=0.72). A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism. CONCLUSIONS: In the present study RNA-Seq was used as a tool to explore the liver transcriptome of pigs with extreme phenotypes for intramuscular fatty acid composition. The differential gene expression analysis showed potential gene networks which affect lipid and fatty acid metabolism. These results may help in the design of selection strategies to improve the sensorial and nutritional quality of pork meat.

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.

Project description:BackgroundIntramuscular fat (IMF) content and its fatty acid (FA) composition are typically controlled by several genes, each with a small effect. In the current study, to pinpoint candidate genes and putative regulators involved in FA composition, we performed a multivariate integrative analysis between intramuscular FA and transcriptome profiles of porcine longissimus dorsi (LD) muscle. We also carried out a combination of network, regulatory impact factor (RIF), in silico prediction of putative target genes, and functional analyses to better support the biological relevance of our findings.ResultsFor this purpose, we used LD RNA-Seq and intramuscular FA composition profiles of 129 Iberian × Duroc backcrossed pigs. We identified 378 correlated variables (13 FA and 365 genes), including six FA (C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, C18:0, and C16:1n-7) that were among the most interconnected variables in the predicted network. The detected FA-correlated genes include genes involved in lipid and/or carbohydrate metabolism or in regulation of IMF deposition (e.g., ADIPOQ, CHUK, CYCS, CYP4B1, DLD, ELOVL6, FBP1, G0S2, GCLC, HMGCR, IDH3A, LEP, LGALS12, LPIN1, PLIN1, PNPLA8, PPP1R1B, SDR16C5, SFRP5, SOD3, SNW1, and TFRC), meat quality (GALNT15, GOT1, MDH1, NEU3, PDHA1, SDHD, and UNC93A), and transport (e.g., EXOC7 and SLC44A2). Functional analysis highlighted 54 over-represented gene ontology terms, including well-known biological processes and pathways that regulate lipid and carbohydrate metabolism. RIF analysis suggested a pivotal role for six transcription factors (CARHSP1, LBX1, MAFA, PAX7, SIX5, and TADA2A) as putative regulators of gene expression and intramuscular FA composition. Based on in silico prediction, we identified putative target genes for these six regulators. Among these, TADA2A and CARHSP1 had extreme RIF scores and present novel regulators in pigs. In addition, the expression of TADA2A correlated (either positively or negatively) with C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, and that of CARHSP1 correlated (positively) with the C16:1n-7 lipokine. We also found that these two transcription factors share target genes that are involved in lipid metabolism (e.g., GOT1, PLIN1, and TFRC).ConclusionsThis integrative analysis of muscle transcriptome and intramuscular FA profile revealed valuable information about key candidate genes and potential regulators for FA and lipid metabolism in pigs, among which some transcription factors are proposed to control gene expression and modulate FA composition differences.

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Novel Genomic Regions Associated with Intramuscular Fatty Acid Composition in Rabbits.

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Novel Genomic Regions Associated with Intramuscular Fatty Acid Composition in Rabbits.

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