Abstract
The aim of the present study was to detect quantitative trait loci (QTL) for innate and adaptive immunity in pigs. For this purpose, a Duroc × Pietrain F2 resource population (DUPI) with 319 offspring was used to map QTL for the immune traits blood antibodies and interferon-gamma using 122 microsatellites covering all autosomes. Antibodies response to Mycoplasma hyopneumoniae and tetanus toxoid vaccine and the interferon-gamma (IFNG) serum concentration were measured at three different time points and were used as phenotypes. The differences of antibodies and interferon concentration between different time points were also used for the linkage mapping. Line-cross and imprinting QTL analysis, including two-QTL, were performed using QTL Express. A total of 30 QTL (12, 6, and 12 for mycoplasma, tetanus antibody, and IFNG, respectively) were identified at the 5% chromosome-wide-level significant, of which 28 were detected by line-cross and 2 by imprinting model. In addition, two QTL were identified on chromosome 5 using the two-QTL approach where both loci were in repulsion phase. Most QTL were detected on pig chromosomes 2, 5, 11, and 18. Antibodies were increased over time and immune traits were found to be affected by sex, litter size, parity, and month of birth. The results demonstrated that antibody and IFNG concentration are influenced by multiple chromosomal areas. The flanking markers of the QTL identified for IFNG on SSC5 did incorporate the position of the porcine IFNG gene. The detected QTL will allow further research in these QTL regions for candidate genes and their utilization in selection to improve the immune response and disease resistance in pig.
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Almasy L, Blangero J (2009) Human QTL linkage mapping. Genetica 136:333–340
Biscarini F, Bovenhuis H, van Arendonk JA, Parmentier HK, Jungerius AP et al (2010) Across-line SNP association study of innate and adaptive immune response in laying hens. Anim Genet 41:26–38
Bischoff SR, Tsai S, Hardison N, Motsinger-Reif AA, Freking BA et al (2009) Characterization of conserved and nonconserved imprinted genes in swine. Biol Reprod 81(5):906–920
Calsamiglia M, Pijoan C (2000) Colonisation state and colostral immunity to Mycoplasma hyopneumoniae of different parity sows. Vet Rec 146:530–532
Chen ZY, Shie J, Tseng C (2000) Up-regulation of gut-enriched kruppel-like factor by interferon-gamma in human colon carcinoma cells. FEBS Lett 477:67–72
Choi C, Kwon D, Jung K, Ha Y, Lee YH et al (2006) Expression of inflammatory cytokines in pigs experimentally infected with Mycoplasma hyopneumoniae. J Comp Pathol 134:40–46
Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138:963–971
Cook TM, Protheroe RT, Handel JM (2001) Tetanus: a review of the literature. Br J Anaesth 87:477–487
Davis ME, Sears SC, Apple JK, Maxwell CV, Johnson ZB (2006) Effect of weaning age and commingling after the nursery phase of pigs in a wean-to-finish facility on growth, and humoral and behavioral indicators of well-being. J Anim Sci 84:743–756
de Koning DJ, Rattink AP, Harlizius B, van Arendonk JA, Brascamp EW et al (2000) Genome-wide scan for body composition in pigs reveals important role of imprinting. Proc Natl Acad Sci U S A 97:7947–7950
de Koning DJ, Harlizius B, Rattink AP, Groenen MA, Brascamp EW et al (2001) Detection and characterization of quantitative trait loci for meat quality traits in pigs. J Anim Sci 79:2812–2819
de Koning DJ, Carlborg O, Haley CS (2005) The genetic dissection of immune response using gene-expression studies and genome mapping. Vet Immunol Immunopathol 105:343–352
Edfors-Lilja I, Wattrang E, Magnusson U, Fossum C (1994) Genetic variation in parameters reflecting immune competence of swine. Vet Immunol Immunopathol 40:1–16
Edfors-Lilja I, Wattrang E, Marklund L, Moller M, Andersson-Eklund L et al (1998) Mapping quantitative trait loci for immune capacity in the pig. J Immunol 161:829–835
Edfors-Lilja I, Wattrang E, Andersson L, Fossum C (2000) Mapping quantitative trait loci for stress induced alterations in porcine leukocyte numbers and functions. Anim Genet 31:186–193
Feulner JA, Lu M, Shelton JM, Zhang M, Richardson JA et al (2004) Identification of acyloxyacyl hydrolase, a lipopolysaccharide-detoxifying enzyme, in the murine urinary tract. Infect Immun 72:3171–3178
Friedman SM, Crow MK, Tumang JR, Tumang M, Xu YQ et al (1991) Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells. J Exp Med 174:891–900
Green PK, Falls A, Crooks S (1990) Documentation for CRIMAP version 2.4. Washington University School of Medicine, St. Louis, MO
Grosse-Brinkhaus C, Phatsara C, Tholen E, Schellander K (2009) Feinkartierung von QTL für Fleischqualitätsmerkmale auf dem porcinen Chromosom 1 (Finemapping of QTL for meat quality traits on porcine chromosome 1). Züchtungskunde 81:63–68
Hall MA, Norman PJ, Thiel B, Tiwari H, Peiffer A et al (2002) Quantitative trait loci on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18 control variation in levels of T and B lymphocyte subpopulations. Am J Hum Genet 70:1172–1182
Hirooka H, de Koning DJ, van Arendonk JA, Harlizius B, de Groot PN et al (2002) Genome scan reveals new coat color loci in exotic pig cross. J Hered 93:1–8
Hodgins DC, Shewen PE, Dewey CE (2004) Influence of age and maternal antibodies on antibody responses of neonatal piglets vaccinated against Mycoplasma hyopneumoniae. J Swine Health Prod 12:10–16
Holl JW, Cassady JP, Pomp D, Johnson RK (2004) A genome scan for quantitative trait loci and imprinted regions affecting reproduction in pigs. J Anim Sci 82:3421–3429
Jeon JT, Carlborg O, Tornsten A, Giuffra E, Amarger V et al (1999) A paternally expressed QTL affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus. Nat Genet 21:157–158
Kim JJ, Zhao H, Thomsen H, Rothschild MF, Dekkers JC (2005) Combined line-cross and half-sib QTL analysis of crosses between outbred lines. Genet Res 85:235–248
Knott SA, Marklund L, Haley CS, Andersson K, Davies W et al (1998) Multiple marker mapping of quantitative trait loci in a cross between outbred wild boar and large white pigs. Genetics 149:1069–1080
LeRoith D, Yanowski J, Kaldjian EP, Jaffe ES, LeRoith T et al (1996) The effects of growth hormone and insulin-like growth factor I on the immune system of aged female monkeys. Endocrinology 137:1071–1079
Liu G, Jennen DG, Tholen E, Juengst H, Kleinwachter T et al (2007) A genome scan reveals QTL for growth, fatness, leanness and meat quality in a Duroc-Pietrain resource population. Anim Genet 38:241–252
Liu G, Kim JJ, Jonas E, Wimmers K, Ponsuksili S et al (2008) Combined line-cross and half-sib QTL analysis in Duroc-Pietrain population. Mamm Genome 19:429–438
Mallard BA, Wilkie BN, Kennedy BW (1989) Genetic and other effects on antibody and cell mediated immune response in swine leucocyte antigen (SLA)-defined miniature pigs. Anim Genet 20:167–178
Marshall AJ, Miles RJ, Richards L (1995) The phagocytosis of mycoplasmas. J Med Microbiol 43:239–250
Meuwissen TH, Goddard ME (2004) Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data. Genet Sel Evol 36:261–279
Moreau IA, Miller GY, Bahnson PB (2004) Effects of Mycoplasma hyopneumoniae vaccine on pigs naturally infected with M. hyopneumoniae and porcine reproductive and respiratory syndrome virus. Vaccine 22:2328–2333
Nezer C, Moreau L, Brouwers B, Coppieters W, Detilleux J et al (1999) An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs. Nat Genet 21:155–156
O’Connell JR, Weeks DE (1998) PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63:259–266
Outteridge PM (1993) High and low responsiveness to vaccines in farm animals. Immunol Cell Biol 71(Pt 5):355–366
Pinard-van der Laan MH, Bed’hom B, Coville JL, Pitel F, Feve K et al (2009) Microsatellite mapping of QTLs affecting resistance to coccidiosis (Eimeria tenella) in a Fayoumi x White Leghorn cross. BMC Genomics 10:31
Postel-Vinay MC, de Mello Coelho V, Gagnerault MC, Dardenne M (1997) Growth hormone stimulates the proliferation of activated mouse T lymphocytes. Endocrinology 138:1816–1820
Raadsma HW, Thomson PC, Zenger KR, Cavanagh C, Lam MK et al (2009) Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage map and QTL for growth rate and body weight. Genet Sel Evol 41:34
Regula G, Weigel RM, Lichtensteiger CA, Mateus-Pinilla NE, Scherba G et al (2003) Development and Evaluation of a Herd Health Monitoring System for Swine Operations. Illini PorkNet (The online resource for pork industry), University of Illinois Extension. Available at http://www.livestocktrail.uiuc.edu/porknet/paperDisplay.cfm?ContentID=421
Reiner G, Melchinger E, Kramarova M, Pfaff E, Buttner M et al (2002) Detection of quantitative trait loci for resistance/susceptibility to pseudorabies virus in swine. J Gen Virol 83:167–172
Reiner G, Kliemt D, Willems H, Berge T, Fischer R et al (2007) Mapping of quantitative trait loci affecting resistance/susceptibility to Sarcocystis miescheriana in swine. Genomics 89:638–646
Rodriguez F, Quesada O, Poveda JB, Fernandez A, Lorenzo H (2007) Immunohistochemical detection of interleukin-12 and interferon-gamma in pigs experimentally infected with Mycoplasma hyopneumoniae. J Comp Pathol 136:79–82
Ruiz A, Galina L, Pijoan C (2002) Mycoplasma hyopneumoniae colonization of pigs sired by different boars. Can J Vet Res 66:79–85
Scheerlinck JP, Yen HH (2005) Veterinary applications of cytokines. Vet Immunol Immunopathol 108:17–22
Seaton G, Haley CS, Knott SA, Kearsey M, Visscher PM (2002) QTL Express: mapping quantitative trait loci in simple and complex pedigrees. Bioinformatics 18:339–340
Stecher B, Paesold G, Barthel M, Kremer M, Jantsch J et al (2006) Chronic Salmonella enterica serovar Typhimurium-induced colitis and cholangitis in streptomycin-pretreated Nramp1 +/+ mice. Infect Immun 74:5047–5057
Sun HS, Wang L, Rothschild MF, Tuggle CK (1998) Mapping of the natural resistance-associated macrophage protein 1 (NRAMP1) gene to pig chromosome 15. Anim Genet 29:138–140
Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3–9
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. J Anim Sci 82:2213–2228
Tycko B, Morison IM (2002) Physiological functions of imprinted genes. J Cell Physiol 192:245–258
Ulloa L, Doody J, Massague J (1999) Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway. Nature 397:710–713
van Duin D, Medzhitov R, Shaw AC (2006) Triggering TLR signaling in vaccination. Trends Immunol 27:49–55
Virella G, Hyman B (1991) Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay: methodology and applications. J Clin Lab Anal 5:43–48
Wimmers K, Mekchay S, Schellander K, Ponsuksili S (2003) Molecular characterization of the pig C3 gene and its association with complement activity. Immunogenetics 54:714–724
Wimmers K, Jonas E, Schreinemachers HJ, Tesfaye D, Ponsuksili S et al (2008) Verification of chromosomal regions affecting the innate immunity in pigs using linkage mapping. Dev Biol (Basel) 132:279–286
Wimmers K, Murani E, Schellander K, Ponsuksili S (2009) QTL for traits related to humoral immune response estimated from data of a porcine F2 resource population. Int J Immunogenet 36:141–151
Yao Q, Huang Q, Cao Y, Qian P, Chen H (2008) Porcine interferon-gamma protects swine from foot-and-mouth disease virus (FMDV). Vet Immunol Immunopathol 122:309–311
Zhang FW, Cheng HC, Jiang CD, Deng CY, Xiong YZ et al (2007) Imprinted status of pleomorphic adenoma gene-like I and paternal expression gene 10 genes in pigs. J Anim Sci 85:886–890
Acknowledgments
This project was supported by the Gene Dialog project, FUGATO Plus, BMBF, grant No. 0315130C, Germany. The authors are indebted to Miss Nadine Leyer, Institute of Animal Science, University of Bonn, Germany, for her help during the experiment.
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335_2010_9269_MOESM1_ESM.tif
Supplementary file 1 Schematic display of vaccination program and time point of blood sampling from F2 DUPI population (TIFF 1049 kb)
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Uddin, M.J., Grosse-Brinkhaus, C., Cinar, M.U. et al. Mapping of quantitative trait loci for mycoplasma and tetanus antibodies and interferon-gamma in a porcine F2 Duroc × Pietrain resource population. Mamm Genome 21, 409–418 (2010). https://doi.org/10.1007/s00335-010-9269-3
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DOI: https://doi.org/10.1007/s00335-010-9269-3