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Porcine insulin receptor substrate 4 (IRS4) gene: cloning, polymorphism and association study

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Abstract

Using PCR and inverse PCR techniques we obtained a 4,498 bp nucleotide sequence FN424076 encompassing the complete coding sequence of the porcine insulin receptor substrate 4 (IRS4) gene and its proximal promoter. The 1,269 amino acid porcine protein deduced from the nucleotide sequence shares 92% identity with the human IRS4 and possesses the same domains and the same number of tyrosine phosphorylation motifs as the human protein. We detected substitution FN424076:g.96C<G in the promoter region that segregates in Meishan and a synonymous substitution FN424076:g.1829T<C in the coding sequence with allele C present only in Meishan. Linkage mapping placed the IRS4 gene at position 82 cM on the current USDA–USMARC linkage map of porcine chromosome X. Association analyses were performed on 555 animals of 12th–15th generation of the Meishan × Large White cross and showed that both SNPs were highly significantly associated with backfat depth (P = 0.0005) and that the SNP FN424076:g1829T<C was also associated with loin depth (P = 0.017). The Meishan alleles increased back fat depth and decreased loin depth. IRS4 can be considered a positional candidate gene for at least some of the QTL located at the centromeric region of porcine chromosome X.

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References

  1. Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P, Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. FASEB J 15:2099–2111

    Article  PubMed  CAS  Google Scholar 

  2. Cai DS, Dhe-Paganon S, Melendez PA, Lee JS, Shoelson SE (2003) Two new substrates in insulin signalling, IRS5/DOK4 and IRS6/DOK5. J Biol Chem 278:25323–25330

    Article  PubMed  CAS  Google Scholar 

  3. Lavan BE, Fantin VR, Chang ET, Lane WS, Keller SR, Lienhard GE (1997) A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family. J Biol Chem 272:21403–21407

    Article  PubMed  CAS  Google Scholar 

  4. Fantin VR, Lavan BE, Wang Q, Jenkins NJ, Gilbert DJ, Copeland NG, Keller SR, Lienhard GE (1999) Cloning, tissue expression, and chromosomal location of the mouse insulin receptor substrate 4 gene. Endocrinology 140:1329–1337

    Article  PubMed  CAS  Google Scholar 

  5. Schreyer S, Ledwig D, Rakatzi I, Klöting I, Eckel J (2003) Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor. Endocrinology 144:1211–1218

    Article  PubMed  CAS  Google Scholar 

  6. Zhou L, Chen H, Xu P, Cong LN, Sciacchitano S, Yunhua L, Graham D, Jacobs AR, Taylor SI, Quon M (1999) Action of insulin receptor substrate-3 (IRS-3) and IRS-4 to stimulate translocation of GLUT4 in rat adipose tissue. Mol Endocrinol 13:505–514

    Article  PubMed  CAS  Google Scholar 

  7. Numan S, Russell DS (1999) Discrete expression of insulin receptor substrate-4 mRNA in adult rat brain. Mol Brain Res 72:97–102

    Article  PubMed  CAS  Google Scholar 

  8. Bischof JM, Wevrick R (2005) Genome-wide analysis of gene transcription in the hypothalamus. Physiol Genomics 22:191–196

    Article  PubMed  CAS  Google Scholar 

  9. Hu Z, Reecy J (2007) Animal QTLdb: beyond a respiratory–A public platform for QTL comparison and integration with diverse types of structural genomic information. Mamm Genome 18:1–4

    Article  PubMed  Google Scholar 

  10. Čepica S, Reiner G, Bartenschlager H, Moser G, Geldermann H (2003) Linkage and QTL mapping for Sus scrofa chromosome X. J Anim Breed Genet 120(Suppl. 1):144–151

    Google Scholar 

  11. Čepica S, Bartenschlager H, Geldermann H (2007) Mapping of QTL on chromosome X for fat deposition, muscling and growth traits in a wild boar x Meishan F2 family using a high-density gene map. Anim Genet 38:634–638

    Article  PubMed  Google Scholar 

  12. Čepica S, Masopust M, Knoll A, Bartenschlager H, Yerle M, Rohrer GA, Geldermann H (2006) Linkage and RH mapping of 10 genes to a QTL region for fatness and muscling traits on pig chromosome X. Anim Gent 37:603–604

    Article  Google Scholar 

  13. Milan D, Bidanel JP, Iannuccelli N, Riquet J, Amigues Y, Gruand J, Le Roy P, Renard C, Chevalet C (2002) Detection of quantitative trait loci for carcass composition traits in pigs. Genet Sel Evol 34:705–728

    Article  PubMed  CAS  Google Scholar 

  14. Duthie CA, Simm G, Pérez-Enciso M, Doeschl-Wilson A, Kalm E, Knap PW, Rainer R (2009) Genomic scan for quantitative trait loci of chemical and physical body composition and deposition on pig chromosome X including the pseudoautosomal region of males. Genet Sel Evol 41:27. doi:10.1186/1297-9686-41-27

    Article  PubMed  Google Scholar 

  15. Rychlik W, Rhoads RE (1989) A computer program for choosing optimal oligonucleotides for filter hybridisation, sequencing and in vitro amplification of DNA. Nucleic Acids Res 17:8543–8551

    Article  PubMed  CAS  Google Scholar 

  16. Ochman H, Gerber AS, Hartl DL (1988) Genetic applications of an inverse polymerase chain reaction. Genetics 120:621–623

    PubMed  CAS  Google Scholar 

  17. Zdobnov EM, Apweiler R (2001) InterProScan—an integration platform for the signature-recognition methods in InterPro. Bioinformatics 17:847–848

    Article  PubMed  CAS  Google Scholar 

  18. Rohrer GA, Alexander LJ, Keele JW, Smith TP, Beattie CW (1994) A microsatellite linkage map of the porcine genome. Genetics 136:231–245

    PubMed  CAS  Google Scholar 

  19. Geldermann H, Müller E, Moser G, Reiner G, Bartenchlager H, Čepica S, Stratil A, Kuryl J, Moran C, Davoli R, Brunsch C (2003) Genome wide linkage and QTL mapping in porcine F2 families generated from Pietrain, Meishan and Wild Boar crosses. J Anim Breed Genet 120:363–393

    Article  CAS  Google Scholar 

  20. Green P, Falls K, Crooks S (1990) Documentation for CRI-MAP, version 2.4. Washington University School of Medicine, St Louis

    Google Scholar 

  21. Zhao JH (2004) 2LD, GENECOUNTING and HAP: computer programs for linkage disequilibrium analysis. Bioinformatics 20:1325–1326

    Article  PubMed  CAS  Google Scholar 

  22. Goldstein DB, Weale ME (2001) Population genomics: linkage disequilibrium holds the key. Curr Biol 11:R576–R579

    Article  PubMed  CAS  Google Scholar 

  23. Amaral AJ, Menges HJ, Crooijmans RPMA, Heuven HCM, Groenen MAM (2008) Linkage disequilibrium decay and haplotype block structure in the pig. Genetics 179:569–579

    Article  PubMed  CAS  Google Scholar 

  24. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57:289–300

    Google Scholar 

  25. Falconer DS (1989) Introduction to quantitative genetics. Longman Scientific &Technical, Essex

    Google Scholar 

  26. Ma J, Iannuccelli N, Duan Y, Huang W, Guo B, Riquet J, Huang L, Milan D (2010) Recombinational landscape of porcine X chromosome and individual variation in female meiotic recombination associated with haplotypes of Chinese pigs. BMC Genomics 11:159, http://www.biomedcentral.com/1471-2164/11/159

  27. Darvasi A, Weinreb A, Minke V, Weller JI, Soller M (1993) Detecting marker QTL gene effect and map location using a saturated genetic map. Genetics 134:943–951

    PubMed  CAS  Google Scholar 

  28. Rohrer GA, Wise TH, Lunstra DD, Ford JJ (2001) Identification of genomic regions controlling plasma FSH concentrations in Meishan-White Composite boars. Physiol Genomics 6:145–151

    PubMed  CAS  Google Scholar 

  29. Sato S, Oyamada Y, Atsuji K, Nade T, Sato S, Kobayashi E, Mitsuhashi T, Nirasawa K, Komatsuda A, Saito Y, Terai S, Hayashi T, Sugimoto Y (2003) Quantitative trait loci analysis for growth and carcass traits in a Meishan x Duroc F2 resource population. J Anim Sci 81:2938–2949

    PubMed  CAS  Google Scholar 

  30. Fantin VR, Wang Q, Lienhard GE, Keller SR (2000) Mice lacking insulin receptor substrate 4 exhibit mild defects in growth, reproduction, and glucose homeostasis. Am J Physiol Endocrinol Metab 278:E127–E133

    PubMed  CAS  Google Scholar 

  31. Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orbab PC, Klein R, Krone W, Müller-Wieland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289:2122–2125

    Article  PubMed  Google Scholar 

  32. Wauman J, De Smet AS, Catteeuw D, Belsham D, Tavernier J (2008) Insulin receptor substrate 4 couples the leptin receptor to multiple signalling pathways. Mol Endocrinol 22:965–977

    Article  PubMed  CAS  Google Scholar 

  33. Valassi E, Scacchi M, Cavagnini F (2008) Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 18:158–168

    Article  PubMed  CAS  Google Scholar 

  34. Barb CR, Kraeling RR (2004) Role of leptin in the regulation of gonadotropins secretion in farm animals. Anim Reprod Sci 82–83:155–167

    Article  PubMed  Google Scholar 

  35. Barb CR, Hausman GJ, Czaja (2005) Leptin: a metabolic signal affecting central regulation of reproduction in the pig. Domest Anim Endocrinol 29:186–192

    Article  PubMed  CAS  Google Scholar 

  36. Barb CR, Hausman GJ, Lents CA (2008) Energy metabolism and leptin: effects of neuroendocrine regulation of reproduction in the gilts and sows. Reprod Domest Anim 43(Suppl. 2):324–330

    Article  PubMed  Google Scholar 

  37. Friedman JM, Jones PA (2009) MicroRNAs: critical mediators of differentiation, development and diseases. Swiss Med Wkly 139:466–472

    PubMed  CAS  Google Scholar 

  38. Trakooljul N, Ponsuksili S, Schellander K, Wimmers K (2004) Polymorphisms of the porcine androgen receptor gene affecting its amino acid sequence and expression level. Biochim Biophys Acta 1678:94–101

    PubMed  CAS  Google Scholar 

  39. Nonneman D, Rohrer GA, Wise TH, Lunstra DD, Ford JJ (2005) A variant of porcine thyroxine-binding globulin has reduced affinity for thyroxine and is associated with testis size. Biol Reprod 72:214–220

    Article  PubMed  CAS  Google Scholar 

  40. Ponsuksili S, Murani E, Schellander K, Schwerin M, Wimmers K (2005) Identification of functional candidate genes for body composition by expression analyses and evidencing impact by association analysis and mapping. Biochim Biophys Acta 1730:31–41

    PubMed  CAS  Google Scholar 

  41. Mercadé A, Estellé J, Pérez-Enciso M, Varona L, Silió L, Noguera JL, Sánchez A, Folch JM (2006) Characterization of the porcine acyl-CoA synthetase long-chain 4 gene and its association with growth and meat quality traits. Anim Genet 37:219–224

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Petra Šejnohová for technical assistance. This work was supported by the Czech Science Foundation (Grant No. 523/07/0353 and P502/10/1216) and by the Institutional Research Plan of the IAPG AS CR (AV0Z50450515).

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Authors and Affiliations

  1. Institute of Animal Physiology and Genetics AS CR, v.v.i., Liběchov, Czech Republic

    Martin Masopust, Aleš Knoll & Stanislav Čepica

  2. Mendel University in Brno, Brno, Czech Republic

    Zuzana Vykoukalová & Aleš Knoll

  3. Department of Animal Breeding and Biotechnology, University of Hohenheim, Stuttgart, Germany

    Heinz Bartenschlager

  4. Genus plc, 1425, River Road, DeForest, WI, 53532, USA

    Alan Mileham

  5. Genus/PIC, 100, Bluegrass Commons Blvd, Suite 2200, Hendersonville, TN, 37075, USA

    Nader Deeb

  6. USDA Agricultural Research Service, US Meat Animal Research Center, Clay Center, NE, USA

    Gary A. Rohrer

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  1. Martin Masopust
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  8. Stanislav Čepica
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Correspondence to Stanislav Čepica.

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Masopust, M., Vykoukalová, Z., Knoll, A. et al. Porcine insulin receptor substrate 4 (IRS4) gene: cloning, polymorphism and association study. Mol Biol Rep 38, 2611–2617 (2011). https://doi.org/10.1007/s11033-010-0402-x

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  • DOI: https://doi.org/10.1007/s11033-010-0402-x

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