Abstract
Enterotoxigenic Escherichia coli (ETEC) with fimbriae of the F4 family are one of the major causes of diarrhea and death among neonatal and young piglets. Bacteria use the F4 fimbriae to adhere to specific receptors expressed on the surface of the enterocytes. F4 fimbriae exist in three different antigenic variants, F4ab, F4ac, and F4ad, of which F4ac is the most common. Resistance to ETEC F4ab/F4ac adhesion in pigs has been shown to be inherited as an autosomal recessive trait. In previous studies the ETEC F4ab/F4ac receptor locus (F4bcR) was mapped to the q41 region on pig chromosome 13. A polymorphism within an intron of the mucin 4 (MUC4) gene, which is one of the possible candidate genes located in this region, was shown earlier to cosegregate with the F4bcR alleles. Recently, we discovered a Large White boar from a Swiss experimental herd with a recombination between F4bcR and MUC4. A three–generation pedigree including 45 offspring was generated with the aim to use this recombination event to refine the localization of the F4bcR locus. All pigs were phenotyped using the microscopic adhesion test and genotyped for a total of 59 markers. The recombination event was mapped to a 220-kb region between a newly detected SNP in the leishmanolysin-like gene (LMLN g.15920) and SNP ALGA0072075. In this study the six SNPs ALGA0072075, ALGA0106330, MUC13-226, MUC13-813, DIA0000584, and MARC0006918 were in complete linkage disequilibrium with F4bcR. Based on this finding and earlier investigations, we suggest that the locus for F4bcR is located between the LMLN locus and microsatellite S0283.
Similar content being viewed by others
References
Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) Merlin–rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101
Bertschinger HU, Fairbrother JM (1999) Escherichia coli infections. In: Straw BE, D’Allaire S, Mengeling WL, Taylor DJ (eds) Diseases of Swine, 8th edn. Iowa State University Press, Ames, IA, pp 431–468
Bijlsma IG, de Nijs A, van der Meer C, Frik JF (1982) Different pig phenotypes affect adherence of Escherichia coli to jejunal brush borders by K88ab, K88ac, or K88ad antigen. Infect Immun 37:891–894
Edfors-Lilja I, Gustafsson U, Duval-Iflah Y, Ellergren H, Johansson M et al (1995) The porcine intestinal receptor for Escherichia coli K88ab, K88ac: regional localization on chromosome 13 and influence of IgG response to the K88 antigen. Anim Genet 26:237–242
Erickson AK, Baker DR, Bosworth BT, Casey TA, Benfield DA et al (1994) Characterization of porcine intestinal receptors for the K88ac fimbrial adhesion of Escherichia coli as mucin-type sialoglycoproteins. Infect Immun 62:5404–5410
Gibbons RA, Sellwood R, Burrows M, Hunter PA (1977) Inheritance of resistance to neonatal E. coli diarrhoea in the pig: Examination of the genetic system. Theor Appl Genet 51:65–70
Jacobsen M, Kracht SS, Esteso G, Cirera S, Edfors I et al (2010) Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs. Anim Genet 41:21–25
Joller D (2009) Comparative molecular approaches to identify host determinants mediating adhesion of E. coli F4 strains in pigs. Dissertation ETH Zürich number 18518. Available at http://e-collection.ethbib.ethz.ch/eserv/eth:445/eth-445-02.pdf#search=%22Joller%20David%22
Joller D, Jorgensen CB, Bertschinger HU, Bürgi E, Stannarius C et al (2006) Refined linkage mapping of the Escherichia coli F4ac receptor gene on pig chromosome 13. Proceedings of the 30th International Conference for Animal Genetics, Porto Seguro, Brazil, August 20–25, 2006
Joller D, Jorgensen CB, Bertschinger HU, Python P, Edfors I et al (2009) Refined localization of the Escherichia coli F4ab/F4ac receptor locus on pig chromosome 13. Anim Genet 40:749–752
Jørgensen CB, Cirera S, Archibald AL, Anderson L, Fredholm M et al (2004) Porcine polymorphisms and methods for detecting them. International application published under the patent cooperation treaty (PCT), WO2004/048606A2
Jørgensen CB, Cirera S, Anderson SI, Archibald AL, Raudsepp T et al (2003) Linkage and comparative mapping of the locus controlling susceptibility towards E. coli F4ab/ac diarrhoea in pigs. Cytogenet Genome Res 102:157–162
Karlsson KA (1998) Meaning and therapeutic potential of microbial recognition of host glycoconjugates. Mol Microbiol 29:1–11
Luther H, Vögeli P, Hofer A (2009) Increasing genetic E.coli F18 resistance in Swiss pigs. Available at http://www.eaap.org/Barcelona/Book_Abstracts.pdf
Meijerink E, Fries R, Vögeli P, Masabanda J, Wigger G et al (1997) Two alpha(1, 2) fucosyltransferase genes on porcine chromosome 6q11 are closely linked to the blood group inhibitor (S) and Escherichia coli F18 receptor (ECF18R) loci. Mamm Genome 8:736–741
Meijerink E, Neuenschwander S, Fries R, Dinter A, Bertschinger HU et al (2000) A DNA polymorphism influencing alpha(1, 2)fucosyltransferase activity of the pig FUT1 enzyme determines susceptibility of small intestinal epithelium to Escherichia coli F18 adhesion. Immunogenetics 52:129–136
Osek J (1999) Prevalence of virulence factors of Escherichia coli strains isolated from diarrheic and healthy piglets after weaning. Vet Microbiol 68:209–217
Python P, Jorg H, Neuenschwander S, Hagger C, Stricker C et al (2002) Fine-mapping of the intestinal receptor locus for enterotoxigenic Escherichia coli F4ac on porcine chromosome 13. Anim Genet 33:441–447
Ramos AM, Crooijmans RP, Affara NA, Amaral AJ, Archibald AL et al (2009) Design of a high density SNP genotyping assay in the pig using SNPs identified and characterized by next generation sequencing technology. PLoS One 4:e6524
Rasschaert K, Verdonck F, Goddeeris BM, Duchateau L, Cox E (2007) Screening of pigs resistant to F4 enterotoxigenic Escherichia coli (ETEC) infection. Vet Microbiol 123:249–253
Rippinger P, Bertschinger HU, Imberechts H, Nagy B, Sorg I et al (1995) Designations F18ab and F18ac for the related fimbrial types F107, 2134P and 8813 of Escherichia coli isolated from porcine postweaning diarrhoea and from oedema disease. Vet Microbiol 45:281–295
Thiele H, Nürnberg P (2005) HaploPainter: a tool for drawing pedigrees with complex haplotypes. Bioinformatics 21:1730–1732
Vögeli P, Bolt R, Fries R, Stranzinger G (1994) Co-segregation of the malignant hyperthermia and the Arg615-Cys615 mutation in the skeletal muscle calcium release channel protein in five European Landrace and Pietrain pig breeds. Anim Genet 25 Suppl 1:59–66
Vögeli P, Bertschinger HU, Stamm M, Stricker C, Hagger C et al (1996) Genes specifying receptors for F18 fimbriated Escherichia coli, causing oedema disease and postweaning diarrhoea in pigs, map to chromosome 6. Anim Genet 27:321–328
Wang J, Jiang SW, Chen XH, Liu ZL, Peng J (2006) Prevalence of fimbrial antigen (K88 variants, K99 and 987P) of enterotoxigenic Escherichia coli from neonatal and post-weaning piglets with diarrhea in central China. Asian Austral J Anim Sci 19(9):1342–1346
Zhang B, Ren J, Yan X, Huang X, Ji H et al (2008) Investigation of the porcine MUC13 gene: isolation, expression, polymorphisms and strong association with susceptibility to enterotoxigenic Escherichia coli F4ab/ac. Anim Genet 39:258–266
Acknowledgments
We thank Prof. Martien Groenen and his group (Animal Breeding and Genetics, Wageningen University, Wageningen, The Netherlands) for providing the SNP sequences and their positions in the Sscrofa9 assembly. We thank Michael Goe for editing the manuscript and the Genomic Diversity Center (ETH Zurich) for allowing us to use their infrastructure. The study was supported by the Swiss National Science Foundation (grant No. 3100A0-120255/1), by the ETH Zurich, and the SUISAG, Sempach (Dr. Andreas Hofer).
Author information
Authors and Affiliations
Corresponding author
Additional information
A. Rampoldi and M. J. Jacobsen contributed equally to this work.
Rights and permissions
About this article
Cite this article
Rampoldi, A., Jacobsen, M.J., Bertschinger, H.U. et al. The receptor locus for Escherichia coli F4ab/F4ac in the pig maps distal to the MUC4–LMLN region. Mamm Genome 22, 122–129 (2011). https://doi.org/10.1007/s00335-010-9305-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-010-9305-3