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Deciphering the regulation of porcine genes influencing growth, fatness and yield-related traits through genetical genomics

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Abstract

Genetical genomics approaches aim at identifying quantitative trait loci for molecular traits, also known as intermediate phenotypes, such as gene expression, that could link variation in genetic information to physiological traits. In the current study, an expression GWAS has been carried out on an experimental Iberian × Landrace backcross in order to identify the genomic regions regulating the gene expression of those genes whose expression is correlated with growth, fat deposition, and premium cut yield measures in pig. The analyses were conducted exploiting Porcine 60K SNP BeadChip genotypes and Porcine Expression Microarray data hybridized on mRNA from Longissimus dorsi muscle. In order to focus the analysis on productive traits and reduce the number of analyses, only those probesets whose expression showed significant correlation with at least one of the seven phenotypes of interest were selected for the eGWAS. A total of 63 eQTL regions were identified with effects on 36 different transcripts. Those eQTLs overlapping with phenotypic QTLs on SSC4, SSC9, SSC13, and SSC17 chromosomes previously detected in the same animal material were further analyzed. Moreover, candidate genes and SNPs were analyzed. Among the most promising results, a long non-coding RNA, ALDBSSCG0000001928, was identified, whose expression is correlated with premium cut yield. Association analysis and in silico sequence domain annotation support TXNRD3 polymorphisms as candidate to regulate ALDBSSCG0000001928 expression, which can be involved in the transcriptional regulation of surrounding genes, affecting productive and meat quality traits.

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References

  • Angrand PO, Vennin C, Le Bourhis X, Adriaenssens E (2015) The role of long non-coding RNAs in genome formatting and expression. Front Genet 6:165

    Article  PubMed  PubMed Central  Google Scholar 

  • Ayuso M, Fernández A, Núñez Y, Benítez R, Isabel B, Barragán C, Fernández AI, Rey AI, Medrano JF, Cánovas Á, González-Bulnes A, López-Bote C, Ovilo C (2015) Comparative analysis of muscle transcriptome between pig genotypes identifies genes and regulatory mechanisms associated to growth, fatness and metabolism. PLoS One 10:e0145162

    Article  PubMed  PubMed Central  Google Scholar 

  • Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2:28–36

    CAS  PubMed  Google Scholar 

  • Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37:202–208

    Article  Google Scholar 

  • Bass JD, Swcf AJ, Dabney A, Robinson D (2015). qvalue: Q-value estimation for false discovery rate control. R package version 2.2.2

  • Breitling R, Li Y, Tesson BM, Fu J, Wu C, Wiltshire T, Gerrits A, Bystrykh LV, de Haan G, Su AI, Jansen RC (2008) Genetical genomics: spotlight on QTL hotspots. PLoS Genet 4:e1000232

    Article  PubMed  PubMed Central  Google Scholar 

  • Buske FA, Bodén M, Bauer DC, Bailey TL (2010) Assigning roles to DNA regulatory motifs using comparative genomics. Bioinformatics 26:860–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang TH, Huang HY, Hsu JB, Weng SL, Horng JT, Huang HD (2013) An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinform 14(Suppl 2):S4

    CAS  Google Scholar 

  • Corominas J, Ramayo-Caldas Y, Puig-Oliveras A, Pérez-Montarelo D, Noguera JL, Folch JM, Ballester M (2013) Polymorphism in the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs. PLoS One 8:e53687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corominas J, Marchesi JA, Puig-Oliveras A, Revilla M, Estellé J, Alves E, Folch JM, Ballester M (2015) Epigenetic regulation of the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs. Genet Sel Evol 47:20

    Article  PubMed  PubMed Central  Google Scholar 

  • Deng HW, Chen WM, Recker RR (2000) QTL fine mapping by measuring and testing for Hardy–Weinberg and linkage disequilibrium at a series of linked marker loci in extreme samples of populations. Am J Hum Genet 66:1027–1045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espigolan R, Baldi F, Boligon AA, Souza FR, Fernandes Júnior GA, Gordo DG, Venturini GC, de Camargo GM, Feitosa FL, Garcia DA, Tonhati H, Chardulo LA, Oliveira HN, Albuquerque LG (2015) Associations between single nucleotide polymorphisms and carcass traits in Nellore cattle using high-density panels. Genet Mol Res 14:11133–11144

    Article  CAS  PubMed  Google Scholar 

  • Estellé J, Pérez-Enciso M, Mercadé A, Varona L, Alves E, Sánchez A, Folch JM (2006) Characterization of the porcine FABP5 gene and its association with the FAT1 QTL in an Iberian by Landrace cross. Anim Genet 37:589–591

    Article  PubMed  Google Scholar 

  • Fernández AI, Pérez-Montarelo D, Barragán C, Ramayo-Caldas Y, Ibáñez-Escriche N, Castelló A, Noguera JL, Silió L, Folch JM, Rodríguez MC (2012) Genome-wide linkage analysis of QTL for growth and body composition employing the PorcineSNP60 BeadChip. BMC Genet 13:41

    Article  PubMed  PubMed Central  Google Scholar 

  • Fernández AI, Muñoz M, Alves E, Folch JM, Noguera JL, Enciso MP, del Rodríguez MC, Silió L (2014) Recombination of the porcine X chromosome: a high density linkage map. BMC Genet 15:148

    Article  PubMed  PubMed Central  Google Scholar 

  • Fontanesi L, Colombo M, Scotti E, Buttazzoni L, Bertolini F, Dall’Olio S, Davoli R, Russo V (2010) The porcine tribbles homolog 3 (TRIB3) gene: identification of a missense mutation and association analysis with meat quality and production traits in Italian heavy pigs. Meat Sci 86:808–813

    Article  CAS  PubMed  Google Scholar 

  • Garcia de la Serrana D, Johnston IA (2013) Expression of heat shock protein (Hsp90) paralogues is regulated by amino acids in skeletal muscle of Atlantic salmon. PLoS One 8:e74295

    Article  PubMed  PubMed Central  Google Scholar 

  • Guntani A, Matsumoto T, Kyuragi R, Iwasa K, Onohara T, Itoh H, Katusic ZS, Maehara Y (2011) Reduced proliferation of aged human vascular smooth muscle cells–role of oxygen-derived free radicals and BubR1 expression. J Surg Res 170:143–149

    Article  CAS  PubMed  Google Scholar 

  • Guo K, Wang J, Andrés V, Smith RC, Walsh K (1995) MyoD-induced expression of p21 inhibits cyclin-dependent kinase activity upon myocyte terminal differentiation. Mol Cell Biol 15:3823–3829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble WS (2007) Quantifying similarity between motifs. Genome Biol 8:R24

    Article  PubMed  PubMed Central  Google Scholar 

  • Hill WG (2012) Quantitative genetics in the genomics era. Curr Genom 13:196–206

    Article  CAS  Google Scholar 

  • Hong J, Kim D, Cho K, Sa S, Choi S, Kim Y, Park J, Schmidt GS, Davis ME, Chung H (2015) Effects of genetic variants for the swine FABP3, HMGA1, MC4R, IGF2, and FABP4 genes on fatty acid composition. Meat Sci 110:46–51

    Article  CAS  PubMed  Google Scholar 

  • Hu ZL, Dracheva S, Jang W, Maglott D, Bastiaansen J, Rothschild MF, Reecy JM (2005) A QTL resource and comparison tool for pigs: PigQTLDB. Mamm Genome 16:792–800

    Article  PubMed  Google Scholar 

  • Jansen RC, Nap JP (2001) Genetical genomics: the added value from segregation. Trends Genet 17:388–391

    Article  CAS  PubMed  Google Scholar 

  • Karisa BK, Thomson J, Wang Z, Stothard P, Moore SS, Plastow GS (2013) Candidate genes and single nucleotide polymorphisms associated with variation in residual feed intake in beef cattle. J Anim Sci 91:3502–3513

    Article  CAS  PubMed  Google Scholar 

  • Karssen LC, van Duijn CM, Aulchenko YS (2016) The GenABEL Project for statistical genomics. F1000Res 5:914

    Article  PubMed  PubMed Central  Google Scholar 

  • Kipp AP, Müller MF, Göken EM, Deubel S, Brigelius-Flohé R (2012) The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium. Biochim Biophys Acta 1820:1588–1596

    Article  CAS  PubMed  Google Scholar 

  • Kodama K, Horikoshi M, Toda K, Yamada S, Hara K, Irie J, Sirota M, Morgan AA, Chen R, Ohtsu H, Maeda S, Kadowaki T, Butte AJ (2012) Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes. Proc Natl Acad Sci USA 109:7049–7054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lahaye LL, Wouda RR, de Jong AW, Fradkin LG, Noordermeer JN (2012) WNT5 interacts with the Ryk receptors doughnut and derailed to mediate muscle attachment site selection in Drosophila melanogaster. PLoS One 7:e32297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li A, Zhang J, Zhou Z, Wang L, Liu Y, Liu Y (2015) ALDB: a domestic-animal long noncoding RNA database. PLoS One 10:e0124003

    Article  PubMed  PubMed Central  Google Scholar 

  • Martínez-Montes AM, Fernández A, Pérez-Montarelo D, Alves E, Benítez RM, Nuñez Y, Óvilo C, Ibañez-Escriche N, Folch JM, Fernández AI (2016) Using RNA-Seq SNP data to reveal potential causal mutations related to pig production traits and RNA editing. Anim Genet. doi:10.1111/age.12507

    PubMed  Google Scholar 

  • Mercadé A, Estellé J, Noguera JL, Folch JM, Varona L, Silió L, Sánchez A, Pérez-Enciso M (2005) On growth, fatness, and form: a further look at porcine chromosome 4 in an Iberian × Landrace cross. Mamm Genome 16:374–382

    Article  PubMed  Google Scholar 

  • Muñoz M, Fernández AI, Ovilo C, Muñoz G, Rodriguez C, Fernández A, Alves E, Silió L (2010) Non-additive effects of RBP4, ESR1 and IGF2 polymorphisms on litter size at different parities in a Chinese-European porcine line. Genet Sel Evol 42:23

    Article  PubMed  PubMed Central  Google Scholar 

  • Nguyen DT, Lee K, Choi H, Choi MK, Le MT, Song N, Kim JH, Seo HG, Oh JW, Lee K, Kim TH, Park C (2012) The complete swine olfactory subgenome: expansion of the olfactory gene repertoire in the pig genome. BMC Genom 13:584

    Article  CAS  Google Scholar 

  • Ovilo C, Pérez-Enciso M, Barragán C, Clop A, Rodríquez C, Oliver MA, Toro MA, Noruera JL (2000) A QTL for intramuscular fat and backfat thickness is located on porcine chromosome 6. Mamm Genome 11:344–346

    Article  CAS  PubMed  Google Scholar 

  • Óvilo C, Fernández A, Noguera JL, Barragán C, Letón R, Rodríguez C, Mercadé A, Alves E, Folch JM, Varona L, Toro MA (2005) Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in multiple generations of an Iberian by Landrace intercross. Genet Res 85:57–67

    Article  PubMed  Google Scholar 

  • Pang W, Wang Y, Wei N, Xu R, Xiong Y, Wang P, Shen Q, Yang G (2013) Sirt1 inhibits akt2-mediated porcine adipogenesis potentially by direct protein–protein interaction. PLoS One 8:e71576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong EP1, Park JW (2012) Sample size and statistical power calculation in genetic association studies. Genom Inform 10:117–122

    Article  CAS  Google Scholar 

  • Pena RN, Noguera JL, Casellas J, Díaz I, Fernández AI, Folch JM, Ibáñez-Escriche N (2013) Transcriptional analysis of intramuscular fatty acid composition in the longissimus thoracis muscle of Iberian × Landrace back-crossed pigs. Anim Genet 44:648–660

    Article  CAS  PubMed  Google Scholar 

  • Pérez-Enciso M, Misztal I (2011) Qxpak.5: old mixed model solutions for new genomics problems. BMC Bioinforma 12:202

    Article  Google Scholar 

  • Pérez-Montarelo D, Fernández A, Folch JM, Pena RN, Ovilo C, Rodríguez C, Silió L, Fernández AI (2012) Joint effects of porcine leptin and leptin receptor polymorphisms on productivity and quality traits. Anim Genet 43:805–809

    Article  PubMed  Google Scholar 

  • Priori D, Colombo M, Clavenzani P, Jansman AJ, Lallès JP, Trevisi P, Bosi P (2015) The olfactory receptor OR51E1 is present along the gastrointestinal tract of pigs, co-localizes with enteroendocrine cells and is modulated by intestinal microbiota. PLoS One 10:e0129501

    Article  PubMed  PubMed Central  Google Scholar 

  • Puig-Oliveras A, Revilla M, Castelló A, Fernández AI, Folch JM, Ballester M (2016) Expression-based GWAS identifies variants, gene interactions and key regulators affecting intramuscular fatty acid content and composition in porcine meat. Sci Rep 6:31803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin LL, Li XK, Xu J, Mo DL, Tong X, Pan ZC, Li JQ, Chen YS, Zhang Z, Wang C, Long (2012) QM Mechano growth factor (MGF) promotes proliferation and inhibits differentiation of porcine satellite cells (PSCs) by down-regulation of key myogenic transcriptional factors. Mol Cell Biochem 370:221–230

    Article  CAS  PubMed  Google Scholar 

  • Ramos AM, Crooijmans RP, Affara NA, Amaral AJ, Archibald AL, Beever JE, Bendixen C, Churcher C, Clark R, Dehais P, Hansen MS, Hedegaard J, Hu ZL, Kerstens HH, Law AS, Megens HJ, Milan D, Nonneman DJ, Rohrer GA, Rothschild MF, Smith TP, Schnabel RD, Van Tassell CP, Taylor JF, Wiedmann RT, Schook LB, Groenen MA (2009) Design of a high density SNP genotyping assay in the pig using SNPs identified and characterized by next generation sequencing technology. PLoS One 4:e6524

    Article  PubMed  PubMed Central  Google Scholar 

  • Ren X, Zhou L, Terwilliger R, Newton SS, de Araujo IE (2009) Sweet taste signaling functions as a hypothalamic glucose sensor. Front Integr Neurosci 3:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Rutenberg-Schoenberg M, Sexton AN, Simon MD (2016) The properties of long noncoding RNAs that regulate chromatin. Annu Rev Genom Hum Genet 17:69–94

    Article  CAS  Google Scholar 

  • Saura M, Tenesa A, Woolliams JA, Fernández A, Villanueva B (2015) Evaluation of the linkage-disequilibrium method for the estimation of effective population size when generations overlap: an empirical case. BMC Genom 16:922

    Article  Google Scholar 

  • Schön CC, Utz HF, Groh S, Truberg B, Openshaw S, Melchinger AE (2004) Quantitative trait locus mapping based on resampling in a vast maize testcross experiment and its relevance to quantitative genetics for complex traits. Genetics 167:485–498

    Article  PubMed  PubMed Central  Google Scholar 

  • Scimè A, Grenier G, Huh MS, Gillespie MA, Bevilacqua L, Harper ME, Rudnicki MA (2005) Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell Metab 2:283–295

    Article  PubMed  Google Scholar 

  • Stephens M, Smith N, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun R, Chang Y, Yang F, Wang Y, Li H, Zhao Y, Chen D, Wu T, Zhang X, Han Z (2015) A dense SNP genetic map constructed using restriction site-associated DNA sequencing enables detection of QTLs controlling apple fruit quality. BMC Genom 16:747

    Article  Google Scholar 

  • Szczerbal I, Chmurzynska A (2008) Chromosomal localization of nine porcine genes encoding transcription factors involved in adipogenesis. Cytogenet Genome Res 121:150–154

    Article  Google Scholar 

  • Tabangin ME, Woo JG, Martin LJ (2009) The effect of minor allele frequency on the likelihood of obtaining false positives. BMC Proc 3(Suppl 7):S41

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Laere AS, Nguyen M, Braunschweig M, Nezer C, Collette C, Moreau L, Archibald AL, Haley CS, Buys N, Tally M, Andersson G, Georges M, Andersson L (2003) A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Nature 425:832–836

    Article  PubMed  Google Scholar 

  • Varona L, Ovilo C, Clop A, Noguera JL, Pérez-Enciso M, Coll A, Folch JM, Barragán C, Toro MA, Babot D, Sánchez A (2002) QTL mapping for growth and carcass traits in an Iberian by Landrace pig intercross: additive, dominant and epistatic effects. Genet Res 80:145–154

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Lemon WJ, You M (2002) Linkage disequilibrium mapping of novel lung tumor susceptibility quantitative trait loci in mice. Oncogene 21:6858–6865

    Article  CAS  PubMed  Google Scholar 

  • Wewer UM, Thornell LE, Loechel F, Zhang X, Durkin ME, Amano S, Burgeson RE, Engvall E, Albrechtsen R, Virtanen I (1997) Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle. Am J Pathol 151:621–631

    CAS  PubMed  PubMed Central  Google Scholar 

  • Williams RB, Chan EK, Cowley MJ, Little PF (2007) The influence of genetic variation on gene expression. Genome Res 17:1707–1716

    Article  CAS  PubMed  Google Scholar 

  • Würschum T, Kraft T (2014) Cross-validation in association mapping and its relevance for the estimation of QTL parameters of complex traits. Heredity (Edinb) 112:463–468

    Article  Google Scholar 

  • Yachdav G, Kloppmann E, Kajan L, Hecht M, Goldberg T, Hamp T, Hönigschmid P, Schafferhans A, Roos M, Bernhofer M (2014) PredictProtein—an open resource for online prediction of protein structural and functional features. Nucleic Acids Res 42(Web Server issue):W337–W343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan X, Weijun P, Ning W, Yu W, Wenkai R, Gongshe Y (2013) Knockdown of both FoxO1 and C/EBPβ promotes adipogenesis in porcine preadipocytes through feedback regulation. Cell Biol Int 37:905–916

    Article  CAS  PubMed  Google Scholar 

  • Zizola CF, Frey SK, Jitngarmkusol S, Kadereit B, Yan N, Vogel S (2010) Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis. Mol Cell Biol 30:3412–3420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou F, Chai HS, Younkin CS, Allen M, Crook J, Pankratz VS, Carrasquillo MM, Rowley CN, Nair AA, Middha S, Maharjan S, Nguyen T, Ma L, Malphrus KG, Palusak R, Lincoln S, Bisceglio G, Georgescu C, Kouri N, Kolbert CP, Jen J, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD; Alzheimer’s Disease Genetics Consortium, Petersen RC, Graff-Radford NR, Dickson DW, Younkin SG, Ertekin-Taner N (2012) Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants. PLoS Genet 8:e1002707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was funded by Ministerio de Economía y Competitividad (MINECO) project AGL2011-29821-C02 and AGL2014-56369-C2. Ángel Martínez-Montes was funded by a (FPI) PhD grant from the Spanish Ministerio de Ciencia e Innovación. We want to thank Fabián Garcia, Anna Mercadé, and Anna Castelló for technical assistance. We would like to thank all the members of the INIA, IRTA, and UAB institutions who contributed to the generation and sample recollection of the animal materials used in this work.

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Authors and Affiliations

  1. Departamento de Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040, Madrid, Spain

    Angel M. Martínez-Montes, Anixa Muiños-Bühl, Almudena Fernández & Ana I. Fernández

  2. Departament de Ciència Animal i dels Aliments, Facultat de Veterinària, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain

    Josep M. Folch

  3. Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (CRAG), Consorci CSIC-IRTA-UAB-UB, Campus UAB, 08193, Bellaterra, Spain

    Josep M. Folch

  4. Departament de Genètica i Millora Animal, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), 25198, Lleida, Spain

    Noelia Ibáñez-Escriche

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  1. Angel M. Martínez-Montes
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  2. Anixa Muiños-Bühl
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Correspondence to Angel M. Martínez-Montes.

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Martínez-Montes, A.M., Muiños-Bühl, A., Fernández, A. et al. Deciphering the regulation of porcine genes influencing growth, fatness and yield-related traits through genetical genomics. Mamm Genome 28, 130–142 (2017). https://doi.org/10.1007/s00335-016-9674-3

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