BACKGROUND: Independent studies have shown that several single nucleotide polymorphisms (SNP) in the human FTO (fat mass and obesity associated) gene are associated with obesity. SNP have also been identified in the pig FTO gene, among which some are associated with selected fat-deposition traits in F2 crosses and commercial populations. In this study, using both commercial pig populations and an experimental Meishan × Pietrain F2 population, we have investigated the association between one FTO SNP and several growth and carcass traits. Association analyses were performed with the FTO polymorphism either alone or in combination with polymorphisms in flanking loci. METHODS: SNP (FM244720:g.400C>G) in exon 3 of porcine FTO was genotyped by PCR-RFLP and tested for associations with some growth, carcass and fat-related traits. Proportions of genetic variance of four pig chromosome 6 genes (FTO, RYR1, LIPE and TGFB1) on selected traits were evaluated using single- and multi-locus models. RESULTS: Linkage analysis placed FTO on the p arm of pig chromosome 6, approximately 22 cM from RYR1. In the commercial populations, allele C of the FTO SNP was significantly associated with back fat depth and allele G with muscling traits. In the Meishan × Pietrain F2 pigs, heterozygotes with allele C from the Pietrain sows and allele G from the Meishan boar were more significantly associated with fat-related traits compared to homozygotes with allele G from the Pietrain and allele G from the Meishan breed. In single- and multi-locus models, genes RYR1, TGFB1 and FTO showed high associations. The contribution in genetic variance from the polymorphism in the FTO gene was highest for back fat depth, meat area on the musculus longissimus lumborum et thoracis tissues and metabolite glucose-6-phosphate dehydrogenase. CONCLUSIONS: Our results show that in pig, FTO influences back fat depth in the commercial populations, while in the Meishan × Pietrain F2 pigs with a CG genotype, heterosis occurs for several fat-related traits.

Institute of Animal Physiology and Genetics Academy of Sciences of Czech Republic 277 21 Liběchov Czech Republic

Zobrazit více v PubMed

van der Hoeven F, Schimmang T, Volkmann A, Mattei M-G, Kyewski B, Rüther U. Programmed cell death is affected in the novel mouse mutant Fused toes (Ft) Development. 1994;120:2601–2607. PubMed

Peters T, Ausmeier K, Rüther U. Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome. 1999;10:983–986. doi: 10.1007/s003359901144. PubMed DOI

Peters T, Ausmeier K, Dildrop R, Rüther U. The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster. Mamm Genome. 2002;13:186–188. doi: 10.1007/s00335-001-2142-7. PubMed DOI

Gerken T, Girard CA, Tung Y-CL, Webby CJ, Saudek V, Hewitson KS, Yeo GSH, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 2007;318:1469–1472. doi: 10.1126/science.1151710. PubMed DOI PMC

Sanchez-Pulido L, Andrade-Navarro MA. The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochem. 2007;8:23. doi: 10.1186/1471-2091-8-23. PubMed DOI PMC

Wu Q, Saunders RA, Szkudlarek-Mikho M, de la Serna I, Chin K-V. The obesity-associated Fto gene is a transcriptional coactivator. Biochem Biophys Res Commun. 2010;401:390–395. doi: 10.1016/j.bbrc.2010.09.064. PubMed DOI PMC

Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JRB, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch A-M, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin M-R, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJF, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CNA, Doney ASF, Morris AD, Smith GD, Hattersley AT, McCarthy MI. The Wellcome Trust Case Control Consortium. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–894. doi: 10.1126/science.1141634. PubMed DOI PMC

Scuteri A, Sanna S, Chen W-M, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007;3:e115. doi: 10.1371/journal.pgen.0030115. PubMed DOI PMC

Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LMS, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre J-C, Froguel P. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39:724–726. doi: 10.1038/ng2048. PubMed DOI

Hinney A, Nguyen TT, Scherag A, Friedel S, Brönner G, Müller TD, Grallert H, Illig T, Wichmann H-E, Rief W, Schäfer H, Hebebrand J. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE. 2007;2:e1361. doi: 10.1371/journal.pone.0001361. PubMed DOI PMC

Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CNA. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med. 2008;359:2558–2566. doi: 10.1056/NEJMoa0803839. PubMed DOI

Loos RJF, Bouchard C. FTO: the first gene contributing to common forms of human obesity. Obes Rev. 2008;9:246–250. doi: 10.1111/j.1467-789X.2008.00481.x. PubMed DOI

Larder R, Cheung MKM, Tung YCL, Yeo GSH, Coll AP. Where to go with FTO? Trends Endocrinol Metabol. 2011;22:53–59. doi: 10.1016/j.tem.2010.11.001. PubMed DOI

Onteru SK, Fan B, Rothschild MF. SNP detection and comparative linkage mapping of 66 bone-related genes in the pig. Cytogenet Genome Res. 2008;122:122–131. doi: 10.1159/000163089. PubMed DOI

Fontanesi L, Scotti E, Buttazzoni L, Davoli R, Russo V. The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs. Anim Genet. 2009;40:90–93. doi: 10.1111/j.1365-2052.2008.01777.x. PubMed DOI

Fontanesi L, Scotti E, Buttazzoni L, Dall'Olio S, Bagnato A, Lo Fiego DP, Davoli R, Russo V. Confirmed association between a single nucleotide polymorphism in the FTO gene and obesity-related traits in heavy pigs. Mol Biol Rep. 2010;37:461–466. doi: 10.1007/s11033-009-9638-8. PubMed DOI

Archibald AL, Bolund L, Churcher C, Fredholm M, Groenen MAM, Harlizius B, Lee K-T, Milan D, Rogers J, Rothschild MF, Uenishi H, Wang J, Schook LB. for the Swine Genome Sequencing Consortium. Pig genome sequence - analysis and publication strategy. BMC Genomics. 2010;11:438. doi: 10.1186/1471-2164-11-438. PubMed DOI PMC

Fan B, Du Z-Q, Rothschild MF. The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Anim Biotechnol. 2009;20:58–70. doi: 10.1080/10495390902800792. PubMed DOI

Zhang LF, Miao XT, Hua XC, Jiang XL, Lu YP, Xu NY. Polymorphism in 5' regulatory region of the porcine fat mass and obesity associated (FTO) gene is associated with intramuscular fat content in a Jinhua × Pietrain F2 reference population. J Anim Vet Adv. 2009;8:2329–2334.

Sellier P. In: The Genetics of the Pig. Rothschild MF, Ruvinsky A, editor. Wallingford: CAB Intl; 1998. Genetics of meat and carcass traits; pp. 463–510.

Yeaman SJ. Hormone-sensitive lipase - new roles for an old enzyme. Biochem J. 2004;379:11–22. doi: 10.1042/BJ20031811. PubMed DOI PMC

Rosmond R, Chagnon M, Bouchard C, Björntorp P. Increased abdominal obesity, insulin and glucose levels in nondiabetic subjects with a T29C polymorphism of the transforming growth factor-beta(1) gene. Hormone Res. 2003;59:191–194. doi: 10.1159/000069323. PubMed DOI

Long J-R, Liu P-Y, Liu Y-J, Lu Y, Xiong D-H, Elze L, Recker RR, Deng H-W. APOE and TGF-β1 genes are associated with obesity phenotypes. J Med Genet. 2003;40:918–924. doi: 10.1136/jmg.40.12.918. PubMed DOI PMC

Geldermann H, Müller E, Moser G, Reiner G, Bartenschlager H, Cepica S, Stratil A, Kuryl J, Moran C, Davoli R, Brunsch C. Genome-wide linkage and QTL mapping in porcine F2 families generated from Pietrain, Meishan and Wild Boar crosses. J Anim Breed Genet. 2003;120:363–393. doi: 10.1046/j.0931-2668.2003.00408.x. DOI

Green P, Falls K, Crooks S. Documentation for CRI-MAP, Version 2.4. St Louis: Washington University School of Medicine; 1990.

Stupka R, Šprysl M, Pour M. Analysis of the formation of the belly in relation to sex. Czech J Anim Sci. 2004;49:64–70.

Geldermann H, Čepica S, Stratil A, Bartenschlager H, Preuss S. Genome-wide mapping of quantitative trait loci for fatness, fat cell characteristics and fat metabolism in three porcine F2 crosses. Genet Sel Evol. 2010;42:31. doi: 10.1186/1297-9686-42-31. PubMed DOI PMC

Yue G, Stratil A, Kopecny M, Schröffelova D, Schröffel J Jr, Hojny J, Cepica S, Davoli R, Zambonelli P, Brunsch C, Sternstein I, Moser G, Bartenschlager H, Reiner G, Geldermann H. Linkage and QTL mapping for Sus scrofa chromosome 6. J Anim Breed Genet. 2003;120(Suppl 1):45–55.

Zhao F, Miller LM, Chardon P, Rogel-Gaillard C, Louis CF. Five new polymorphic microsatellite markers for pig chromosome 6p. Anim Genet. 1999;30:394–395. PubMed

Meyers SN, Rogatcheva MB, Larkin DM, Yerle M, Milan D, Hawken RJ, Schook LB, Beever JE. Piggy-BACing the human genome - II. A high-resolution, physically anchored, comparative map of the porcine autosomes. Genomics. 2005;86:739–752. doi: 10.1016/j.ygeno.2005.04.010. PubMed DOI

Du Z-Q, Fan B, Zhao X, Amoako R, Rothschild MF. Association analyses between type 2 diabetes genes and obesity traits in pigs. Obesity. 2009;17:323–329. PubMed

Mohrmann M, Roehe R, Knap PW, Looft H, Plastow GS, Kalm E. Quantitative trait loci associated with AutoFOM grading characteristics, carcass cuts and chemical body composition during growth of Sus scrofa. Anim Genet. 2006;37:435–443. doi: 10.1111/j.1365-2052.2006.01492.x. PubMed DOI

Paszek AA, Wilkie PJ, Flickinger GH, Miller LM, Louis CF, Rohrer GA, Alexander LJ, Beattie CW, Schook LB. Interval mapping of carcass and meat quality traits in a divergent swine cross. Anim Biotechnol. 2001;12:155–165. doi: 10.1081/ABIO-100108342. PubMed DOI

Óvilo C, Fernández A, Noguera JL, Barragán C, Letón R, Rodríguez C, Mercadé A, Alves E, Folch JM, Varona L, Toro M. Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in multiple generations of an Iberian by Landrace intercross. Genet Res. 2005;85:57–67. doi: 10.1017/S0016672305007330. PubMed DOI

Stratil A, Horák P, Filkuková J, Van Poucke M, Bartenschlager H, Peelman LJ, Geldermann H. Partial genomic structure, mutation analysis and mapping of the porcine inhibitor of DNA binding genes ID1, ID2, ID3 and ID4. Anim Genet. 2010;41:558–559. doi: 10.1111/j.1365-2052.2010.02065.x. PubMed DOI

Brem G, Brenig B. Molecular genotype diagnosis of the malignant hyperthermia syndrome for efficient breeding of stress-resistant pigs. Wiener Tierärztl Monatsschr. 1992;79:301–305.

Otsu K, Phillips MS, Khanna VK, De Leon S, MacLennan DH. Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia. Genomics. 1992;13:835–837. doi: 10.1016/0888-7543(92)90163-M. PubMed DOI

Knoll A, Stratil A, Nebola M, Čepica S. Characterization of a polymorphism in exon 1 of the porcine hormone-sensitive lipase (LIPE) gene. Anim Genet. 1998;29:462–463. PubMed

Kopečný M, Stratil A, Van Poucke M, Bartenschlager H, Geldermann H, Peelman LJ. PCR-RFLPs, linkage and RH mapping of the porcine TGFB1 and TGFBR1 genes. Anim Genet. 2004;35:253–255. doi: 10.1111/j.1365-2052.2004.01130.x. PubMed DOI