Skip to main content

KRT8, FAF1 and PTH1R gene polymorphisms are associated with leg weakness traits in pigs

Abstract

The liability to lesions of dysfunctions of bone and joints in pigs, summarized as leg weakness and mostly expressed as osteochondrosis, is an animal welfare and economic issue in pig production. The objective of this study was to identify polymorphisms in the functional and positional candidate genes keratin 8 (KRT8), Fas-associated factor 1 (FAF1) and parathyroid hormone type I receptor (PTH1R) and to evaluate their association with leg weakness traits. Therefore, osteochondrosis lesions were scored in animals of a Duroc × Pietrain F2 population (DuPi; n = 310) and commercial herds of the breed Large White (n = 298). In addition, bone mineralization traits were observed in DuPi population. SNPs were identified in genes KRT8 (g.8,039G > A), FAF1 (g.380,914T > C) and PTH1R (c.1,672C > T). KRT8 showed significant association with bone mineral density and content (P ≤ 0.05). FAF1 was association with OC lesions score of all joints inspected (P ≤ 0.05). PTH1R showed significant dominance effects on OC lesion scores of the distal femur articular cartilage (P = 0.01) and epiphysis of the distal ulna (P = 0.05) as well as sums of scores of all joints (OCsum, P = 0.04) and assignment to groups of either severely or gently affected animals (OCcat, P = 0.01). This study reveals clear genetic-statistical evidence for a link of KRT8, FAF1 and PTH1R with some of leg weakness related traits in pigs.

This is a preview of subscription content, access via your institution.

Fig. 1

Abbreviations

OC:

Osteochondrosis

KRT8 :

Keratin 8

FAF1 :

Fas-associated factor 1

PTH1R :

Parathyroid hormone type I receptor

References

  1. Fukawa K, Kusuhara S (2001) The genetic and non-genetic aspects of leg weakness and osteochondrosis in pigs—review. Asian Aust J Anim Sci 14:114–122

    Google Scholar 

  2. Yazdi MH, Lundeheim N, Rydhmer L, Ringmar-Cederberg E, Johansson K (2000) Survival of Swedish Landrace and Yorkshire sows in relation to osteochondrosis: a genetic study. J Anim Sci 71:1–9

    Google Scholar 

  3. Nakano T, Brennan JJ, Aherne FX (1987) Leg weakness and osteochondrosis in swine: a review. Can J Anim Sci 67:883–901

    Article  Google Scholar 

  4. Stern S, Lundeheim N, Johansson K, Andersson K (1995) Osteochondrosis and leg weakness in pigs selected for lean tissue growth rate. Livest Prod Sci 44(1):45–52

    Article  Google Scholar 

  5. Ytrehus B, Carlson CS, Ekman S (2007) Etiology and pathogenesis of osteochondrosis. Vet Pathol 44(4):429–448. doi:10.1354/vp.44-4-429

    PubMed  Article  CAS  Google Scholar 

  6. Bickhardt K (1998) Exertional myopathy and osteochondrosis of pigs as a result of breeding for growth rate. Tierärztliche umschau 53:129–134

    Google Scholar 

  7. Uhlhorn H, Dalin G, Lundeheim N, Ekman S (1995) Osteochondrosis in wild boar-Swedish Yorkshire crossbred pigs (F2 generation). Acta Vet Scand 36(1):41–53

    PubMed  CAS  Google Scholar 

  8. Arnbjerg J (2007) Effect of a low-growth rate on the frequency of osteochondrosis in Danish Landrace pigs (short communication). Archiv Tierzucht 50(1):105–111

    Google Scholar 

  9. Draper DD, Rothschild MF, Christian LL (1991) Effects of divergent selection for limb weakness on bone and muscle cross-sectional areas in Duroc swine. Am J Vet Res 52:164–168

    PubMed  CAS  Google Scholar 

  10. Lundeheim N (1987) Genetic analysis of osteochondrosis and leg weakness in the Swedish pig progeny testing scheme. Acta Agriculturae Scandinavica 37(2):159–173. doi:10.1080/00015128709436552

    Article  Google Scholar 

  11. Jørgensen B, Andersen S (2000) Genetic parameters for osteochondrosis in Danish Landrace and Yorkshire boars and correlations with leg weakness and production traits. J Anim Sci 73:427–434

    Google Scholar 

  12. Reiland S, Ordell N, Lundeheim N, Olsson SE (1978) Heredity of osteochondrosis, body constitution and leg weakness in the pig. A correlative investigation using progeny testing. Acta Radiol Suppl 358:123–137

    PubMed  CAS  Google Scholar 

  13. Fan B, Onteru S, Mote B, Serenius T, Stalder K, Rothschild M (2009) Large-scale association study for structural soundness and leg locomotion traits in the pig. Genet Sel Evol 41(1):14

    PubMed  Article  Google Scholar 

  14. Fan B, Onteru SK, Nikkilä MT, Stalder KJ, Rothschild MF (2009) Identification of genetic markers associated with fatness and leg weakness traits in the pig. Anim Genet 40(6):967–970. doi:10.1111/j.1365-2052.2009.01932.x

    PubMed  Article  CAS  Google Scholar 

  15. Onteru SK, Fan B, Mote B, Serenius T, Nikkilae M, Stalder KJ, Rothschild MF (2008) SNP discovery in genes affecting leg health traits in pigs. Dev Biol (Basel) 132:337–342

    CAS  Google Scholar 

  16. Laenoi W, Rangkasenee N, Uddin M, Cinar M, Phatsara C, Tesfaye D, Scholz A, Tholen E, Looft C, Mielenz M, Sauerwein H, Wimmers K, Schellander K (2011) Association and expression study of MMP3, TGFβ1 and COL10A1 as candidate genes for leg weakness-related traits in pigs. Mol Biol Rep 39(4):3893–3901. doi:10.1007/s11033-011-1168-5

    Google Scholar 

  17. Chu K, Niu X, Williams LT (1995) A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc Natl Acad Sci USA 92(25):11894–11898

    PubMed  Article  CAS  Google Scholar 

  18. Zhang L, Zhou FF, van Laar T, Zhang J, van Dam H, ten Dijke P (2011) Fas-associated factor 1 antagonizes Wnt signaling by promoting beta-catenin degradation. Mol Biol Cell 22(9):1617–1624. doi:10.1091/mbc.E10-12-0985

    PubMed  Article  CAS  Google Scholar 

  19. Lee GJ, Archibald AL, Garth GB, Law AS, Nicholson D, Barr A, Haley CS (2003) Detection of quantitative trait loci for locomotion and osteochondrosis-related traits in Large White × Meishan pigs. Anim Sci 76:155–165

    CAS  Google Scholar 

  20. Mannstadt M, Jüppner H, Gardella TJ (1999) Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol Renal Physiol 277(5):F665–F675

    CAS  Google Scholar 

  21. Harrington EK, Lunsford LE, Svoboda KKH (2004) Chondrocyte terminal differentiation, apoptosis, and type × collagen expression are downregulated by parathyroid hormone. Anat Rec A Discov Mol Cell Evol Biol 281(2):1286–1295. doi:10.1002/ar.a.20129

    PubMed  Article  Google Scholar 

  22. Rangkasenee N, Murani E, Brunner R, Schellander K, Luther H, Hofer A, Ponsuksili S, Wimmers K (2011) Genome-wide association and expression analyses reveal candidate genes for leg weakness in pigs. 12th Day of the doctoral student. Breitschuh & Kock, Dummerstorf, pp 67–70

    Google Scholar 

  23. Luther H, Schwörer D, Hofer A (2007) Heritabilities of osteochondral lesions and genetic correlations with production and exterior traits in station-tested pigs. Animal 1(08):1105–1111. doi:10.1017/S1751731107000493

    Google Scholar 

  24. Laenoi W, Uddin MJ, Cinar MU, Phatsara C, Tesfaye D, Scholz AM, Tholen E, Looft C, Mielenz M, Sauerwein H, Schellander K (2010) Molecular characterization and methylation study of matrix gla protein in articular cartilage from pig with osteochondrosis. Gene 459(1–2):24–31. doi:10.1016/j.gene.2010.03.009

    Google Scholar 

  25. Theune C (2008) Phenotypisation of a F2-resource population for molecular genetic studies regarding leg weakness in pigs: histological scoring of articular cartilage and comparison with exterior and performance traits as well as mRNA expression analyses of some functional candidates genes. Dissertation, University of Veterinary Medicine, Hannover

  26. Lösel D, Küchenmeister U, Hartung M, Nürnberg G, Bellmann O, Albrecht E (2007) Non-invasive determination of body composition in pigs using a Norland XR-26 bone densitometer. Archiv Tierzucht 50(1):487–500

    Google Scholar 

  27. Mitchell AD, Scholz AM (2009) Relationships among dual-energy X-ray absorptiometry, bioelectrical impedance and ultrasound measurements of body composition of swine. Archiv Tierzucht 52(1):28–39

    Google Scholar 

  28. Christensen OF, Busch ME, Gregersen VR, Lund MS, Nielsen B, Vingborg RKK, Bendixen C (2010) Quantitative trait loci analysis of osteochondrosis traits in the elbow joint of pigs. Animal 4(3):417–424. doi:10.1017/S1751731109991248

    PubMed  Article  CAS  Google Scholar 

  29. Moon MC, Yau L, Wright B, Zahradka P (2008) Injury-induced expression of cytokeratins 8 and 18 by vascular smooth muscle cells requires concurrent activation of cytoskeletal and growth factor receptors. Can J Physiol Pharmacol 86(5):223–231. doi:10.1139/y08-019

    PubMed  Article  CAS  Google Scholar 

  30. Jahn L, Kreuzer J, von Hodenberg E, Kubler W, Franke W, Allenberg J, Izumo S (1993) Cytokeratins 8 and 18 in smooth muscle cells. Detection in human coronary artery, peripheral vascular, and vein graft disease and in transplantation-associated arteriosclerosis. Arterioscler Thromb 13(11):1631–1639. doi:10.1161/01.atv.13.11.1631

    PubMed  Article  CAS  Google Scholar 

  31. Laroche M, Pouilles J, Ribot C, Bendayan P, Bernard J, Boccalon H, Mazieres B (1994) Comparison of the bone mineral content of the lower limbs in men with ischaemic atherosclerotic disease. Clin Rheumatol 13(4):611–614. doi:10.1007/bf02243003

    PubMed  Article  CAS  Google Scholar 

  32. Nishizawa Y, Morii H (1997) Osteoporosis and atherosclerosis in chronic renal failure. Osteoporos Int 7:188–192. doi:10.1007/bf03194370

    Article  Google Scholar 

  33. Liu F, Kohlmeier S, Wang CY (2008) Wnt signaling and skeletal development. Cell Signal 20(6):999–1009. doi:10.1016/j.cellsig.2007.11.011

    PubMed  Article  CAS  Google Scholar 

  34. Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ, Bonewald LF, Kneissel M (2010) Osteocyte Wnt/β-catenin signaling is required for normal bone homeostasis. Mol Cell Biol 30(12):3071–3085. doi:10.1128/mcb.01428-09

    PubMed  Article  CAS  Google Scholar 

  35. Patterson EK, Hodsman AB, Hendy GN, Canaff L, Bringhurst FR, Fraher LJ (2010) Functional analysis of a type 1 parathyroid hormone receptor intracellular tail mutant [KRK(484–6)AAA]: effects on second messenger generation and cellular targeting. Bone 46(4):1180–1187. doi:10.1016/j.bone.2009.12.005

    PubMed  Article  CAS  Google Scholar 

  36. Iida-Klein A, Guo J, Xie LY, Jüppner H, Potts JT, Kronenberg HM, Bringhurst FR, Abou-Samra AB, Segre GV (1995) Truncation of the carboxyl-terminal region of the rat parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of adenylyl cyclase but not phospholipase C. J Biol Chem 270(15):8458–8465. doi:10.1074/jbc.270.15.8458

    PubMed  Article  CAS  Google Scholar 

  37. Guo J, Chung U-I, Kondo H, Bringhurst FR, Kronenberg HM (2002) The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without activating phospholipase C. Dev Cell 3(2):183–194. doi:10.1016/s1534-5807(02)00218-6

    PubMed  Article  CAS  Google Scholar 

  38. Andersson-Eklund L, Uhlhorn H, Lundeheim N, Dalin G, Andersson L (2000) Mapping quantitative trait loci for principal components of bone measurements and osteochondrosis scores in a wild boar × Large White intercross. Genet Res 75:223–230

    PubMed  Article  CAS  Google Scholar 

  39. Mao H, Guo Y, Yang G, Yang B, Ren J, Liu S, Ai H, Ma J, Brenig B, Huang L (2008) A genome-wide scan for quantitative trait loci affecting limb bone lengths and areal bone mineral density of the distal femur in a White Duroc × Erhualian F2 population. BMC Genet 9(1):63

    PubMed  Article  Google Scholar 

Download references

Acknowledgments

The authors thank the German Federal Ministry of Education and Research (BMBF) and the Förderverein Biotechnologieforschung der Deutschen Schweineproduktion e.V. (FBF) for financial support (FUGATOplus—GeneFL, FKZ 0315135B).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Klaus Wimmers.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rangkasenee, N., Murani, E., Brunner, R. et al. KRT8, FAF1 and PTH1R gene polymorphisms are associated with leg weakness traits in pigs. Mol Biol Rep 40, 2859–2866 (2013). https://doi.org/10.1007/s11033-012-2301-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2301-9

Keywords

  • Association
  • Candidate gene
  • Leg weakness
  • Swine
  • Osteochondrosis