Investigation of the porcine MUC13 gene: isolation, expression, polymorphisms and strong association with susceptibility to enterotoxigenic Escherichia coli F4ab/ac

Abstract

Enterotoxigenic Escherichia coli (ETEC) F4ab and F4ac are major determinants of piglet diarrhoea. The locus for the ETEC F4ab/ac receptor has been mapped to SSC13q41. MUC13 is a transmembrane mucin expressed predominantly in the epithelial surface of the gastrointestinal tract and the MUC13 gene was assigned to SSC13q41, supporting it as a positional candidate gene for the ETEC F4ab/ac receptor. We herein determined the complete 2679-bp cDNA of pig MUC13, and proved that it was most highly expressed in the jejunum and moderately expressed in the trachea, stomach and liver. Furthermore, 13 MUC13 polymorphisms were identified in 19 founder animals of a White Duroc x Erhualian resource population, and a total of 727 F(2) animals with in vitro ETEC F4ab/ac adhesion phenotypes in this population were genotyped for three identified MUC13 polymorphisms including c.576C>T, c.908A>G and c.935A>C. The transmission disequilibrium test showed that the MUC13 alleles and haplotypes were significantly associated with susceptibility/resistance to ETEC F4ab/ac, especially between haplotype [C;G;A] and susceptibility to ETEC F4ac (P = 8.0e-18). Animals inheriting this haplotype were predominantly susceptible to ETEC F4ac (n = 291/303). Moreover, nearly all animals homozygous for haplotype [T;G;C] (n = 39/41) and a majority of those with the [C;A;A]/[T;G;C] haplotype pair (n = 79/88) were resistant to ETEC F4ab. Our results indicated that MUC13 is in strong linkage disequilibrium with the ETEC F4ab/ac receptor locus and provided potential markers for selection of ETEC F4ab/ac-resistant animals in the pig breeding scheme.

Association of B3GNT5 Polymorphisms with Susceptibility to ETEC F4ab/ac in the White Duroc × Erhualian Intercross and 15 Outbred Pig Breeds

“…P-values given as -log 10 P and plotted against the alleles and haplotypes of four SNPs Odds ratio c 95% confidence interval whereas they were susceptible to F4ab (102/186) (Table 3). Thus, as we proposed in previous reports Wang et al 2007;Zhang et al 2008), the ETEC F4ab and F4ac receptors could be encoded by two linked but distinct genes. It should be noted that none of the B3GNT5 polymorphisms displayed association with F4ab/ac adhesion phenotypes in Western pig breeds.…”

“…Those encoding mucin-like sialoglycoproteins and transferrin-like proteins (Erickson et al 1994;Grange and Mouricout 1996) in the refined region are most likely positional candidate genes. Several candidate genes, including MUC4 (Jørgensen et al 2004;Peng et al 2007), MUC13 (Zhang et al 2008), and TFRC ), have been investigated; however, the causal gene and variant remain unknown.…”

A genome-wide association analysis for susceptibility of pigs to enterotoxigenic Escherichia coli F41

“…The presence of F41 fimbriae on the surface of the bacteria was verified by a routine agglutination assay. The microscopic enterocyte adhesion test that determined ETEC F41 adhesion phenotypes was described in previous work (Zhang et al, 2008). Briefly, a 2 cm segment of the jejunum of each animal was collected within 30 min postmortem, then the epithelia brush borders were isolated.…”

Detection of quantitative trait loci for porcine susceptibility to enterotoxigenic Escherichia coli F41 in a White Duroc × Chinese Erhualian resource population

“…Bacteria were firstly cultured in broth culture medium, and enriched on an inclined BBL (Jingkehongda, Beijing, China) medium containing 1.9% agar for 18 h at 378C. A microscopic enterocyte adhesion test was used to record adhesion phenotypes of the F41 ETEC strain in the experimental pigs as described in Zhang et al (2008). Briefly, a 2-cm segment of the jejunum was collected from each animal within 30 min post mortem and then epithelia brush borders were isolated.…”

“…Moreover, several candidate genes (Joller et al, 2006;Peng et al, 2007;Zhang et al, 2008) for the F4ab/ac and F18 receptors (Meijerink et al, 2000) have been proposed. a These authors contributed equally to this study.…”