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Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs

Published online by Cambridge University Press:  20 July 2012

L. Fontanesi*
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
F. Bertolini
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
E. Scotti
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
P. Trevisi
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
L. Buttazzoni
Affiliation:
CRA, Centro di Ricerca per la Produzione delle Carni e il Miglioramento Genetico, Via Salaria 31, 00015 Monterotondo Scalo, Roma, Italy
S. Dall'Olio
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
R. Davoli
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
P. Bosi
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
V. Russo
Affiliation:
Department of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy
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Abstract

The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes the prohormone convertase 1/3 enzyme that processes prohormones into functional hormones that, in turn, regulate central and peripheral energy metabolism. Mutations in the human PCSK1 gene cause severe monogenic obesity or confer risk of obesity. We herein investigated the porcine PCSK1 gene with the aim of identifying polymorphisms associated with fat deposition and production traits in Italian heavy pigs. By re-sequencing about 5.1 kb of this gene in 21 pigs of different breeds, we discovered 14 polymorphisms that were organized in nine haplotypes, clearly distributed in two clades of putative European and Asian origin. Then we re-mapped this gene on porcine chromosome 2 and analysed its expression in several tissues including gastric oxyntic mucosa of weanling pigs in which PCSK1 processes the pre-pro-ghrelin into ghrelin, which in turn is involved in the control of feed intake and energy metabolism. Association analyses between PCSK1 single-nucleotide polymorphisms (SNPs) and production, carcass and several other traits were conducted on five groups of pigs from three different experimental designs, for a total of 1221 animals. Results indicated that the analysed SNPs were associated (P < 0.01 or P < 0.05) with several traits including backfat thickness and visible intermuscular fat in Italian Duroc (ID) and growth performances in Italian Large White (ILW) and in ILW × Italian Landrace pigs. However, the effects estimated in the ILW were opposite to the effects reported in the ID pigs. Suggestive association (P < 0.10) was observed with muscle cathepsin B activity, opening, if confirmed, potential applications to reduce the excessive softness defect of the green hams that is of particular concern for the processing industry. The results obtained supported the need to further investigate the PCSK1 gene to fully exploit the value of its variability and apply this information in pig breeding programmes.

Type
Breeding and genetics
Copyright
Copyright © The Animal Consortium 2012

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References

Bagnato, A, Schiavini, F, Rossoni, A, Maltecca, C, Dolezal, M, Medugorac, I, Sölkner, J, Russo, V, Fontanesi, L, Friedman, A, Soller, M, Lipkin, E 2008. Quantitative trait loci affecting milk yield and protein percentage in a three-country Brown Swiss population. Journal of Dairy Science 91, 767783.CrossRefGoogle Scholar
Barrett, JC, Fry, B, Maller, J, Daly, MJ 2005. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263265.Google Scholar
Benzinou, M, Creemers, JW, Choquet, H, Lobbens, S, Dina, C, Durand, E, Guerardel, A, Boutin, P, Jouret, B, Heude, B, Balkau, B, Tichet, J, Marre, M, Potoczna, N, Horber, F, Le Stunff, C, Czernichow, S, Sandbaek, A, Lauritzen, T, Borch-Johnsen, K, Andersen, G, Kiess, W, Körner, A, Kovacs, P, Jacobson, P, Carlsson, LM, Walley, AJ, Jørgensen, T, Hansen, T, Pedersen, O, Meyre, D, Froguel, P 2008. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nature Genetics 40, 943945.CrossRefGoogle ScholarPubMed
Bosi, P, Gremokolini, C, Trevisi, P, Mazzoni, M, Bonilauri, P, Sarli, G, Casini, L 2004. Oral challenge with E. coli K88 as a tool to assess growth and health performance in feeding trials of weaned pigs. Journées Recherche Porcine 36, 125132.Google Scholar
Bruun, CS, Jørgensen, CB, Nielsen, VH, Andersson, L, Fredholm, M 2006. Evaluation of the porcine melanocortin 4 receptor (MC4R) gene as a positional candidate for a fatness QTL in a cross between Landrace and Hampshire. Animal Genetics 37, 359362.Google Scholar
Chang, YC, Chiu, YF, Shih, KC, Lin, MW, Sheu, WH, Donlon, T, Curb, JD, Jou, YS, Chang, TJ, Li, HY, Chuang, LM 2010. Common PCSK1 haplotypes are associated with obesity in the Chinese population. Obesity (Silver Spring) 18, 14041409.Google Scholar
Ciobanu, DC, Lonergan, SM, Huff-Lonergan, EJ 2011. Genetics of meat quality and carcass traits. In The genetics of the pig (ed. MF Rothschild and A Ruvinsky), pp. 355389. CAB International, New York.CrossRefGoogle Scholar
Clutter, AC 2011. Genetics of performance traits. In The genetics of the pig (ed. MF Rothschild and A Ruvinsky), pp. 325354. CAB International, New York.Google Scholar
Du, ZQ, Fan, B, Zhao, X, Amoako, R, Rothschild, MF 2009. Association analyses between type 2 diabetes genes and obesity traits in pigs. Obesity (Silver Spring) 17, 323329.CrossRefGoogle ScholarPubMed
Ekine, C, Rowe, S, Bishop, S, de Koning, D-J 2010. What is the best phenotype for genome-wide association studies in data with defined pedigree? Proceedings of the 9th World Congress of Genetics Applied to Livestock Production, 1–6 August, Leipzig, Germany. Communication no. 263.Google Scholar
Fan, B, Du, ZQ, Rothschild, MF 2009a. The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Animal Biotechnology 20, 5870.Google Scholar
Fan, B, Onteru, SK, Nikkilä, MT, Stalder, KJ, Rothschild, MF 2009b. Identification of genetic markers associated with fatness and leg weakness traits in the pig. Animal Genetics 40, 967970.Google Scholar
Fan, B, Onteru, SK, Plastow, GS, Rothschild, MF 2009c. Detailed characterization of the porcine MC4R gene in relation to fatness and growth. Animal Genetics 40, 401409.CrossRefGoogle ScholarPubMed
Farooqi, IS, Volders, K, Stanhope, R, Heuschkel, R, White, A, Lank, E, Keogh, J, O'Rahilly, S, Creemers, JW 2007. Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. Journal of Clinical Endocrinology and Metabolism 92, 33693373.Google Scholar
Fernando, RL, Nettleton, D, Southey, BR, Dekkers, JC, Rothschild, MF, Soller, M 2004. Controlling the proportion of false positives in multiple dependent tests. Genetics 166, 611619.Google Scholar
Fontanesi, L, Colombo, M, Beretti, F, Russo, V 2008a. Evaluation of post mortem stability of porcine skeletal muscle RNA. Meat Science 80, 13451351.Google Scholar
Fontanesi, L, Davoli, R, Nanni Costa, L, Beretti, F, Scotti, E, Tazzoli, M, Tassone, F, Colombo, M, Buttazzoni, L, Russo, V 2008b. Investigation of candidate genes for glycolytic potential of porcine skeletal muscle: association with meat quality and production traits in Italian Large White pigs. Meat Science 80, 780787.Google Scholar
Fontanesi, L, Scotti, E, Buttazzoni, L, Davoli, R, Russo, V 2009. The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs. Animal Genetics 40, 9093.Google Scholar
Fontanesi, L, Colombo, M, Scotti, E, Buttazzoni, L, Bertolini, F, Dall'Olio, S, Davoli, R, Russo, V 2010a. 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 Science 86, 806813.Google Scholar
Fontanesi, L, Scotti, E, Buttazzoni, L, Dall'Olio, S, Bagnato, A, Lo Fiego, DP, Davoli, R, Russo, V 2010b. Confirmed association between a single nucleotide polymorphism in the FTO gene and obesity-related traits in heavy pigs. Molecular Biology Reports 37, 461466.Google Scholar
Fontanesi, L, Scotti, E, Buttazzoni, L, Dall'Olio, S, Davoli, R, Russo, V 2010c. A single nucleotide polymorphism in the porcine cathepsin K (CTSK) gene is associated with back fat thickness and production traits in Italian Duroc pigs. Molecular Biology Reports 37, 491495.Google Scholar
Fontanesi, L, Speroni, C, Buttazzoni, L, Scotti, E, Dall'Olio, S, Nanni Costa, L, Davoli, R, Russo, V 2010d. The IGF2 intron3-g.3072G>A polymorphism is not the only Sus scrofa chromosome 2p mutation affecting meat production and carcass traits in pigs: evidences from the effects of a cathepsin D (CTSD) gene polymorphism. Journal of Animal Science 88, 22352245.Google Scholar
Fontanesi, L, Colombo, M, Tognazzi, L, Scotti, E, Buttazzoni, L, Dall'Olio, S, Davoli, R, Russo, V 2011a. The porcine TBC1D1 gene: mapping, SNP identification, and association study with meat, carcass and production traits in Italian heavy pigs. Molecular Biology Reports 38, 14251431.Google Scholar
Fontanesi, L, Scotti, E, Speroni, C, Buttazzoni, L, Russo, V 2011b. A selective genotyping approach identifies single nucleotide polymorphisms in porcine chromosome 2 genes associated with production and carcass traits in Italian heavy pigs. Italian Journal of Animal Science 10, e15.Google Scholar
Forbes, JM 1995. Voluntary food intake and diet selection in farm animals, second edition (ed. JM Forbes). CAB International, Wallingford, Oxon, UK.Google Scholar
Gagnon, J, Mayne, J, Mbikay, M, Woulfe, J, Chrétien, M 2009. Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine. Regulatory Peptides 152, 5460.Google Scholar
Hamasima, N, Mikawa, A, Suzuki, H, Suzuki, K, Uenishi, H, Awata, T 2008. A new 4016-marker radiation hybrid map for porcine-human genome analysis. Mammalian Genome 19, 5160.Google Scholar
Hawken, RJ, Murtaugh, J, Flickinger, GH, Yerle, M, Robic, A, Milan, D, Gellin, J, Beattie, CW, Schook, LB, Alexander, LJ 1999. A first-generation porcine whole-genome radiation hybrid map. Mammalian Genome 10, 824830.Google Scholar
Heni, M, Haupt, A, Schäfer, SA, Ketterer, C, Thamer, C, Machicao, F, Stefan, N, Staiger, H, Häring, HU, Fritsche, A 2010. Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion. BMC Medical Genetics 11, 86.Google Scholar
Houston, RD, Cameron, ND, Rance, KA 2004. A melanocortin-4 receptor (MC4R) polymorphism is associated with performance traits in divergently selected Large White pig populations. Animal Genetics 35, 386390.Google Scholar
Hu, ZL, Reecy, JM 2007. Animal QTLdb: beyond a repository. A public platform for QTL comparisons and integration with diverse types of structural genomic information. Mammalian Genome 18, 14.Google Scholar
Israel, C, Weller, JI 2002. Estimation of quantitative trait loci effects in dairy cattle populations. Journal of Dairy Science 85, 12851297.Google Scholar
Jackson, RS, Creemers, JW, Ohagi, S, Raffin-Sanson, ML, Sanders, L, Montague, CT, Hutton, JC, O'Rahilly, S 1997. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nature Genetics 16, 303306.CrossRefGoogle ScholarPubMed
Kilpeläinen, TO, Bingham, SA, Khaw, KT, Wareham, NJ, Loos, RJ 2009. Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study. Human Molecular Genetics 18, 34963501.Google Scholar
Kim, KS, Larsen, N, Short, T, Plastow, G, Rothschild, MF 2000. A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits. Mammalian Genome 11, 131135.CrossRefGoogle ScholarPubMed
Kojima, M, Kangawa, K 2005. Ghrelin: structure and function. Physiological Reviews 85, 495522.CrossRefGoogle ScholarPubMed
Lee, SS, Chen, Y, Moran, C, Cepica, S, Reiner, G, Bartenschlager, H, Moser, G, Geldermann, H 2003. Linkage and QTL mapping for Sus scrofa chromosome 2. Journal of Animal Breeding and Genetics 120 (suppl. 1), 1119.Google Scholar
Liu, G, Jennen, DG, Tholen, E, Juengst, H, Kleinwächter, T, Hölker, M, Tesfaye, D, Un, G, Schreinemachers, HJ, Murani, E, Ponsuksili, S, Kim, JJ, Schellander, K, Wimmers, K 2007. A genome scan reveals QTL for growth, fatness, leanness and meat quality in a Duroc-Pietrain resource population. Animal Genetics 38, 241252.CrossRefGoogle Scholar
Lloyd, DJ, Bohan, S, Gekakis, N 2006. Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice. Human Molecular Genetics 15, 18841893.CrossRefGoogle ScholarPubMed
Malek, M, Dekkers, JC, Lee, HK, Baas, TJ, Rothschild, MF 2001. A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. I. Growth and body composition. Mammalian Genome 12, 630636.CrossRefGoogle ScholarPubMed
Milan, D, Hawken, R, Cabau, C, Leroux, S, Genet, C, Lahbib, Y, Tosser, G, Robic, A, Hatey, F, Alexander, L, Beattie, C, Schook, L, Yerle, M, Gellin, J 2000. IMpRH server: an RH mapping server available on the Web. Bioinformatics 16, 558559.Google Scholar
Muller, L, Lindberg, I 1999. The cell biology of the prohormone convertases PC1 and PC2. Progress in Nucleic Acid Research and Molecular Biology 63, 69108.Google Scholar
Qi, Q, Li, H, Loos, RJ, Liu, C, Hu, FB, Wu, H, Yu, Z, Lin, X 2010. Association of PCSK1 rs6234 with obesity and related traits in a Chinese Han population. PLoS One 5, e10590.Google Scholar
Rink, A, Eyer, K, Roelofs, B, Priest, KJ, Sharkey-Brockmeier, KJ, Lekhong, S, Karajusuf, EK, Bang, J, Yerle, M, Milan, D, Liu, WS, Beattie, CW 2006. Radiation hybrid map of the porcine genome comprising 2035 EST loci. Mammalian Genome 17, 878885.Google Scholar
Rothschild, MF, Hu, ZL, Jiang, Z 2007. Advances in QTL mapping in pigs. International Journal of Biological Sciences 3, 192197.Google Scholar
Rozas, J, Sanchez-DelBarrio, JC, Messeguer, X, Rozas, R 2003. DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19, 24962497.Google Scholar
Russo, V, Nanni Costa, L 1995. Suitability of pig meat for salting and the production of quality processed products. Pig News & Information 16, 7N26N.Google Scholar
Russo, V, Buttazzoni, L, Baiocco, C, Davoli, R, Nanni Costa, L, Schivazappa, C, Virgili, R 2000. Heritability of muscular cathepsin B activity in Italian Large White pigs. Journal of Animal Breeding and Genetics 117, 3742.CrossRefGoogle Scholar
Russo, V, Fontanesi, L, Scotti, E, Beretti, F, Davoli, R, Nanni Costa, L, Virgili, R, Buttazzoni, L 2008. Single nucleotide polymorphisms in several porcine cathepsin genes are associated with growth, carcass, and production traits in Italian Large White pigs. Journal of Animal Science 86, 33003314.CrossRefGoogle ScholarPubMed
Salfen, BE, Carroll, JA, Keisler, DH 2003. Endocrine responses to short-term feed deprivation in weanling pigs. Journal of Endocrinology 178, 541551.Google Scholar
Scamuffa, N, Calvo, F, Chrétien, M, Seidah, NG, Khatib, AM 2006. Proprotein convertases: lessons from knockouts. FASEB Journal 20, 19541963.Google Scholar
Shimogiri, T, Kiuchi, S, Hiraiwa, H, Hayashi, T, Takano, Y, Maeda, Y, Yasue, H 2006. Assignment of 117 genes from HSA5 to the porcine IMpRH map and generation of a dense human–pig comparative map. Animal Genetics 37, 503508.Google Scholar
Steiner, DF, Rouillé, Y, Gong, Q, Martin, S, Carroll, R, Chan, SJ 1996. The role of prohormone convertases in insulin biosynthesis: evidence for inherited defects in their action in man and experimental animals. Diabetes and Metabolism 22, 94104.Google Scholar
Stephens, M, Smith, NJ, Donnelly, P 2001. A new statistical method for haplotype reconstruction from population data. American Journal of Human Genetics 68, 978989.CrossRefGoogle ScholarPubMed
Stuber, CW, Edwards, MD, Wendel, JF 1987. Molecular-marker facilitated investigations of quantitative trait loci in maize. II. Factors influencing yield and its component traits. Crop Science 27, 639648.Google Scholar
Switonski, M, Stachowiak, M, Cieslak, J, Bartz, M, Grzes, M 2010. Genetics of fat tissue accumulation in pigs: a comparative approach. Journal of Applied Genetics 51, 153168.Google Scholar
Tal-Stein, R, Fontanesi, L, Dolezal, M, Scotti, E, Bagnato, A, Russo, V, Canavesi, F, Friedmann, A, Soller, M, Lipkin, E 2010. A genome scan for QTL affecting milk somatic cell count in Israeli and Italian Holstein cows by means selective DNA pooling with multiple marker mapping. Journal of Dairy Science 93, 49134927.CrossRefGoogle ScholarPubMed
Tamura, K, Dudley, J, Nei, M, Kumar, S 2007. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Molecular Biology and Evolution 24, 15961599.CrossRefGoogle ScholarPubMed
Thomsen, H, Lee, HK, Rothschild, MF, Malek, M, Dekkers, JC 2004. Characterization of quantitative trait loci for growth and meat quality in a cross between commercial breeds of swine. Journal of Animal Science 82, 22132228.Google Scholar
Thomsen, H, Reinsch, N, Xu, N, Looft, C, Grupe, S, Kühn, C, Brockmann, GA, Schwerin, M, Leyhe-Horn, B, Hiendleder, S, Erhardt, G, Medjugorac, I, Russ, I, Förster, M, Brenig, B, Reinhardt, F, Reents, R, Blümel, J, Averdunk, G, Kalm, E 2001. Comparison of estimated breeding values, daughter yield deviations and de-regressed proofs within a whole genome scan for QTL. Journal of Animal Breeding and Genetics 118, 357370.CrossRefGoogle Scholar
Tortereau, F, Gilbert, H, Heuven, HC, Bidanel, JP, Groenen, MA, Riquet, J 2011. Number and mode of inheritance of QTL influencing backfat thickness on SSC2p in Sino-European pig pedigrees. Genetics Selection Evolution 43, 11.Google Scholar
Trevisi, P, Corrent, E, Messori, S, Casini, L, Bosi, P 2010. Healthy newly weaned pigs require more tryptophan to maximize feed intake if they are susceptible to Escherichia coli K88. Livestock Science 134, 236238.Google Scholar
Trevisi, P, Melchior, D, Mazzoni, M, Casini, L, De Filippi, S, Minieri, L, Lalatta-Costerbosa, G, Bosi, P 2009. A tryptophan-enriched diet improves feed intake and growth performance of susceptible weanling pigs orally challenged with E. coli K88. Journal of Animal Science 87, 148156.Google Scholar
Virgili, R, Schivazappa, C 2002. Muscle traits for long matured dried meats. Meat Science 62, 331343.Google Scholar
Wren, AM, Small, CJ, Abbott, CR, Dhillo, WS, Seal, LJ, Cohen, MA, Batterham, RL, Taheri, S, Stanley, SA, Ghatei, MA, Bloom, SR 2001. Ghrelin causes hyperphagia and obesity in rats. Diabetes 50, 25402547.Google Scholar
Yerle, M, Pinton, P, Robic, A, Alfonso, A, Palvadeau, Y, Delcros, C, Hawken, R, Alexander, L, Beattie, C, Schook, L, Milan, D, Gellin, J 1998. Construction of a whole-genome radiation hybrid panel for high-resolution gene mapping in pigs. Cytogenetics and Cell Genetics 82, 182188.Google Scholar
Zhu, X, Cao, Y, Voogd, K, Steiner, DF 2006. On the processing of proghrelin to ghrelin. Journal of Biological Chemistry 281, 3886738870.Google Scholar
Zhu, X, Zhou, A, Dey, A, Norrbom, C, Carroll, R, Zhang, C, Laurent, V, Lindberg, I, Ugleholdt, R, Holst, JJ, Steiner, DF 2002. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proceedings of the National Academy of Science of the USA 99, 1029310298.Google Scholar
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