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1.
Niu X  Li Y  Ding X  Zhang Q 《Animal genetics》2011,42(5):552-555
Enterotoxigenic Escherichia coli expressing F4 fimbriae is the major cause of diarrhoea in neonatal and post-weaning piglets. Previous studies have revealed that the loci controlling the F4ab/F4ac receptors are located on SSC13q41, between markers SW207 and S0283. In this study, we refined their positions in a two generation population containing 366 piglets of three breeds (Large White, Landrace, and Songliao Black). Nine microsatellite markers within this region were selected from the MARC (U.S. Meat Animal Research Center) porcine linkage map, and the pedigree disequilibrium test was employed for fine-mapping. The F4abR gene was located in the interval between S0283 and SW1833, a 4.8-cM region, and the F4acR gene was located in the interval between S0283 and SW1876, a 1.6-cM region. Our results also suggest that the F4ab/F4ac receptors might be controlled by two different but closely linked loci. The results of microsatellite-based haplotype analysis in the corresponding region show that some specific haplotypes were overwhelmingly present in the adhesive or non-adhesive animals, indicating that there are mutations within the identified regions that are strongly associated with the F4ab/ac phenotypes.  相似文献   

2.
Diarrhoea in newborn and weaned pigs caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbriae leads to considerable losses in pig production. In this study, we refined the mapping of the receptor locus for ETEC F4ab/F4ac adhesion ( F4bcR ) by joint analysis of Nordic and Swiss data. A total of 236 pigs from a Nordic experimental herd, 331 pigs from a Swiss experimental herd and 143 pigs from the Swiss performing station were used for linkage analysis. Genotyping data of six known microsatellite markers, two newly developed markers ( MUC4gt and HSA125gt ) and an intronic SNP in MUC4 ( MUC4-8227 ) were used to create the linkage map. The region for F4bcR was refined to the interval SW207 – S0075 on pig chromosome 13. The most probable position of F4bcR was in the SW207 – MUC4 region. The order of six markers was supported by physical mapping on the BAC fingerprint contig from the Wellcome Trust Sanger Institute. Thus, the region for F4bcR could be reduced from 26 to 14 Mb.  相似文献   

3.
Neonatal diarrhea caused by enterotoxigenic Escherichia coli(ETEC)F4 is a common and serious disease,resulting in significant economical loss in the pig industry.The locus encoding ETEC F4 receptor has been mapped to pig chromosome(SSC)13q41,and one of the most significantly linked markers is S0075.In this study,we selected three genes including SLC12A8,MYLK and KPNA1 from a chromosomal region flanking S0075 on SSC13 to develop pig specific sequence tagged sites(STS). Seven single nucleotide polymorphisms were identified in the three pig STS using DNA of four full-sib susceptible and resistant animals in a White Duroc×Erhualian intercross.All grandparents,parents and 755 offspring in the intercross were genotyped for three polymorphisms,including SLC12A8 g.159A>G,MYLK g.1673A>G and KPNA1 g.306A>G.Family-based transmission disequilibrium test(TDT) revealed that all polymorphisms and the corresponding haplotypes are significantly associated with ETEC F4ab/ac(especially F4ac)brush border adhesion phenotypes,indicating that these polymor- phism are in linkage disequlibrium with causal mutation(s)of the gene encoding ETEC F4ab/ac receptor. Our results strengthen the evidence for the involvement of SSC13q41 in high acquiring risk of ETEC F4ab/ac infection,and provide novel polymorphic markers for fine mapping of the ETEC F4ab/ac receptor locus.  相似文献   

4.
Segregation at the loci coding for the K88ab and K88ac small intestinal receptors to E. coli adhesins (K88abR, K88acR) and at the transferrin (TF) locus was studied in 38 pig families including 273 piglets. The TF locus showed a segregation deviation towards the B variant while each of the K88 receptors behaved as a single autosomal dominant gene. Recombinants between K88abR and K88acR provide evidence that they are under the control of two different loci. Thirty-two triple backcross families were selected to test linkage and estimate recombination rates (θ). Our results demonstrate that the two K88 receptor loci are closely linked (θ= 0.02) with a maximum lod score value (Zm) of 46.0. In addition, they are linked to the TF locus, θ= 0.14, Zm= 19.6 for the K88abR locus and θ= 0.16, Zm= 17.9 for the K88acR locus. The estimated recombination rates, smaller in males than in females, are consistent with the order TF-K88abR-K88acR. This linkage thus localizes the K88 loci, as the TF locus, on chromosome 13.  相似文献   

5.
The loci encoding the porcine intestinal receptors for Escherichia coli K88ab and K88ac (K88abR and K88acR) were firmly assigned to chromosome 13 by linkage analysis using a three-generation pedigree. The linear order of these loci and seven other markers on chromosome 13 was determined by multipoint analyses. The K88abR and K88acR loci were tightly linked with the K88abR locus localized 7·4 cM (sex average) proximal to the transferrin locus. The results, together with previous reports from two other groups, provide an unequivocal assignment of the K88 receptor loci to chromosome 13, and reject a previous assignment to chromosome 4. Pigs possessing the receptor had a slightly higher specific IgG response to the K88 antigen after an intramuscular immunization with an E. coli vaccine.  相似文献   

6.
Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13 . Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4 , to be associated with F4ab/ac susceptibility.  相似文献   

7.
Enteric Escherichia coli infections are a highly relevant cause of disease and death in young pigs. Breeding genetically resistant pigs is an economical and sustainable method of prevention. Resistant pigs are protected against colonization of the intestine through the absence of receptors for the bacterial fimbriae, which mediate adhesion to the intestinal surface. The present work aimed at elucidation of the mode of inheritance of the F4ad receptor which according to former investigations appeared quite confusing. Intestines of 489 pigs of an experimental herd were examined by a microscopic adhesion test modified in such a manner that four small intestinal sites instead of one were tested for adhesion of the fimbrial variant F4ad. Segregation analysis revealed that the mixed inheritance model explained our data best. The heritability of the F4ad phenotype was estimated to be 0.7±0.1. There are no relations to the strong receptors for variants F4ab and F4ac. Targeted matings allowed the discrimination between two F4ad receptors, that is, a fully adhesive receptor (F4adRFA) expressed on all enterocytes and at all small intestinal sites, and a partially adhesive receptor (F4adRPA) variably expressed at different sites and often leading to partial bacterial adhesion. In pigs with both F4ad receptors, the F4adRPA receptor is masked by the F4adRFA. The hypothesis that F4adRFA must be encoded by at least two complementary or epistatic dominant genes is supported by the Hardy–Weinberg equilibrium statistics. The F4adRPA receptor is inherited as a monogenetic dominant trait. A comparable partially adhesive receptor for variant F4ab (F4abRPA) was also observed but the limited data did not allow a prediction of the mode of inheritance. Pigs were therefore classified into one of eight receptor phenotypes: A1 (F4abRFA/F4acR+/F4adRFA); A2 (F4abRFA/F4acR+/F4adRPA); B (F4abRFA/F4acR+/F4adR); C1 (F4abRPA/F4acR/F4adRFA); C2 (F4abRPA/F4acR/F4adRPA); D1 (F4abR/F4acR/F4adRFA); D2 (F4abR/F4acR/F4adRPA); E (F4abR/F4acR/F4adR).  相似文献   

8.
Zhang B  Ren J  Yan X  Huang X  Ji H  Peng Q  Zhang Z  Huang L 《Animal genetics》2008,39(3):258-266
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.  相似文献   

9.
蒋隽  施启顺  柳小春  黄生强  贺长青 《遗传》2004,26(2):160-162
采用13号染色体上与K88ab和K88ac受体基因连锁的2对引物(S0223和S0068),研究沙子岭猪和大约克猪的遗传差异性。结果表明,2个猪种在2个基因座均存在多态性,其基因杂合度和Shannon信息指数存在很大差异,而中外猪种的K88ab和K88ac受体基因也存在遗传差异,这2对引物可望作为K88ab和K88ac受体基因的遗传标记。Abstract: The genetic variation of ETEC F4 receptor in Shaziling and Yorkshire breeds were studied using two microsatellite markers(S0223 and S0068). The results showed that there were polymorphisms in the two markers, and there were great variations of the gene heterozygosity and Shannon information index in the two breeds. It was also reported that there were differences in K88ab and K88ac receptors in Chinese native breeds and foreign breeds, so the two markers might be the genetic markers of F4 receptor gene.  相似文献   

10.
In 1995, Edfors-Lilja and coworkers mapped the locus for the E. COLI K88ab (F4ab) and K88ac (F4ac) intestinal receptor to pig chromosome 13 (SSC13). Using the same family material we have refined the map position to a region between the microsatellite markers Sw207 and Sw225. Primers from these markers were used to screen a pig BAC library and the positive clones were used for fluorescent in situ hybridization (FISH) analysis. The results of the FISH analysis helped to propose a candidate gene region in the SSC13q41-->q44 interval. Shotgun sequencing of the FISH-mapped BAC clones revealed that the candidate region contains an evolutionary breakpoint between human and pig. In order to further characterise the rearrangements between SSC13 and human chromosome 3 (HSA3), detailed gene mapping of SSC13 was carried out. Based on this mapping data we have constructed a detailed comparative map between SSC13 and HSA3. Two candidate regions on human chromosome 3 have been identified that are likely to harbour the human homologue of the gene responsible for susceptibility towards E. COLI F4ab/ac diarrhoea in pigs.  相似文献   

11.
The F4ac receptor locus (F4acR), which encodes susceptibility or resistance to Escherichia coli diarrhoea, is inherited as an autosomal recessive monogenetic trait. F4acR is localized on pig chromosome 13 (SSC13q41–q44) near the MUC13 gene. Two flanking markers (CHCF1 and ALGA0106330) with a high linkage disequilibrium (LD) with F4acR were found to be effective for the genetic identification of F4ac‐resistant pigs in the Swiss Large White breed (one recombinant out of 2034 genotyped pigs). Three recombinant boars, one each from the Duroc, Swiss Landrace and Piétrain breeds, were genotyped with seven different markers and phenotyped by means of a microscopic adhesion test. Only ALGA0072075, CHCF1 and CHCF3 indicated the correct phenotype. To test the effect of the resistance allele on production traits, 530 Large White pigs from the national test station were investigated. A significant difference existed among the F4acR locus genotypes in the intramuscular fat content of the longissimus dorsi muscle, whereas no other production traits were influenced by the resistance allele. The frequency of the CHCF1‐C and ALGA0106330‐A alleles associated with resistance in the Swiss Large White population was 60%, which is advantageous for implementing this trait in a breeding programme to select for E. coli F4ac‐resistant animals. The selection of resistant pigs should start on the male side due to the inability of resistant sows to produce sufficient amounts of protecting antibodies in the colostrum. Selection of genetically F4ac‐resistant pigs is a sustainable and suitable alternative to decreasing animal loss and antibiotic use due to diarrhoea.  相似文献   

12.
大肠杆菌F4在3个品种猪中的黏附模式   总被引:1,自引:0,他引:1  
大肠杆菌F4是引起仔猪断奶前腹泻的一种主要细菌,F4黏附于小肠上皮细胞是其致病的前提。小肠上皮细胞的F4受体是由常染色体上的基因编码的,如果无受体,仔猪表现为大肠杆菌抗性。为了研究黏附的遗传机制,本实验利用大白、长白、松辽黑猪的小肠刷状缘细胞与F4ab、F4ac、F4ad进行离体黏附实验,结果发现3品种(系)猪之间黏附情况存在显著差别(P<0.01),松辽黑猪以非黏附型为主,而长白猪中黏附型比例较高,在同一品种猪内,3种菌株的黏附比例在松辽黑猪内和大白猪内有极显著差异,但在长白猪中无显著差异。从3种细菌与刷状缘的黏附模式来看,F4ab、F4ac和F4ad分别有3种不同的受体,它们可能是由3个不同的基因座编码的。  相似文献   

13.
Brush borders or enterocytes obtained from the small intestine of 248 pedigreed pigs were tested by adhesion assay in vitro with enterotoxigenic Escherichia (E.) coli strains, each expressing one of the three K88 pilus variants K88ab, K88ac and K88ad. All pigs were classified as belonging to one of the four adhesion phenotypes: I--K88ab(-), ac(-), ad(-); II--K88ab(-), ac(-), ad(+); III--K88ab(+), ac(+), ad(-); and IV--K88ab(+), ac(+), ad(+). Serum or red cells were typed for 15 blood group systems: A-O, B, C, D, E, F, G, H, I, J, K, L, M, N and O; for 11 biochemical polymorphisms: PI1, PI2, PO1A, A1BG, GPI, PGD, TF, HPX, ADA, PGM and AMY; the polymorphism at the IGHG1 locus. Linkage analysis was performed between the alleles at the locus (loci) specifying K88 receptors able to bind one or more different serological types of K88 E. coli and alleles for markers at other loci. Linkage was demonstrated between the locus for the L blood group system and the locus (loci) for K88 E. coli receptors (Z = 3.24), adding one locus (loci) to the previously identified linkage group IV (LGIV) [L-SLB]. The maximum likelihood estimate of the recombination fraction (theta) was 0.23. No evidence was found for linkage between any of the other biochemical and immunogenetic markers and the receptor locus (loci) of K88 E. coli.  相似文献   

14.
Summary. Brush borders, enterocytes, or both preparations obtained from the small intestine of 345 pedigreed pigs, carrying components of seven breeds, were tested by adhesion assay in vitro with 6–32 enteropathogenic Escherichia coli strains, each expressing one of the three K88 pilus antigens, K88ab, K88ac and K88ad. With few exceptions, all pigs were classified as belonging to one of four adhesion phenotypes: I – corresponding to K88ab(-),ac(-),ad(-); II – K88ab(-),ac(+),ad(+); III – K88ab(+),ac(+),ad(-); and IV – K88ab(+),ac(+),ad(+). The non-adhering phenotype I was found to be the most frequent among the pigs tested, with the exception of one commercial herd, and this phenotype seems to be inherited as a recessive trait. The remaining three phenotypes are adhering, or are susceptible to adherence by one K88 variant, K88ad (phenotype II), by two variants, K88ab,ac (phenotype III), or by all three K88 variants, K88ab,ac,ad (phenotype IV). Phenotype II was found to be at low frequency, whereas III and IV occurred with similar frequencies. While the prevailing phenomenon was the bacterial adhesion to all, or none, of the brush borders, some pigs exhibited both adhering and non-adhering brush borders, a mixed adherence phenotype. Preliminary segregation data, obtained from the F1 generation, seem to indicate that phenotypes III and IV correspond to two haplotypes with genes at two or three closely linked loci respectively. An alternative hypothesis is that the phenotypes [II and IV are expressions of alleles at a single locus, each allele specifying a receptor able to bind two or three different serological types of K88 E. coli.  相似文献   

15.
Brush borders, enterocytes, or both preparations obtained from the small intestine of 345 pedigreed pigs, carrying components of seven breeds, were tested by adhesion assay in vitro with 6-32 enteropathogenic Escherichia coli strains, each expressing one of the three K88 pilus antigens, K88ab, K88ac and K88ad. With few exceptions, all pigs were classified as belonging to one of four adhesion phenotypes: I I--corresponding to K88ab(-),ac(-),ad(-); II--K88ab(-),ac(-),ad(+); III--K88ab(+),ac(+),ad(-); and IV--K88ab(+),ac(+),ad(+). The non-adhering phenotype I was found to be the most frequent among the pigs tested, with the exception of one commercial herd, and this phenotype seems to be inherited as a recessive trait. The remaining three phenotypes are adhering, or are susceptible to adherence by one K88 variant, K88ad (phenotype II), by two variants, K88ab, ac (phenotype III), or by all three K88 variants, K88ab,ac,ad (phenotype IV). Phenotype II was found to be at low frequency, whereas III and IV occurred with similar frequencies. While the prevailing phenomenon was the bacterial adhesion to all, or none, of the brush borders, some pigs exhibited both adhering and non-adhering brush borders, a mixed adherence phenotype. Preliminary segregation data, obtained from the F1 generation, seem to indicate that phenotypes III and IV correspond to two haplotypes with genes at two or three closely linked loci respectively. An alternative hypothesis is that the phenotypes III and IV are expressions of alleles at a single locus, each allele specifying a receptor able to bind two or three different serological types of K88 E. coli.  相似文献   

16.
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?Cgeneration 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.  相似文献   

17.
Using a porcine radiation hybrid panel, we assigned the mucin 4 (MUC4) gene to SSC13q41, which harbours the enterotoxigenic Escherichia coli (ETEC) F4ab/ac receptor locus. In addition, we identified two SNPs in intron 17 of MUC4 (DQ124298:g.243A>G and DQ124298:g.334A>G) in the parental population of a White Duroc x Erhualian cross. Association analysis showed that the MUC4 g.243A>G mutation was strongly associated with ETEC F4ab/ac, and especially with F4ac adhesion phenotypes in the White Duroc x Erhualian resource population, indicating that this polymorphism was in a significant linkage disequlibrium with the ETEC F4ab/ac receptor locus. Because of different linkage disequlibrium values between the ETEC F4ab and F4ac adhesion phenotypes and the MUC4 g.243A>G mutation, we argue that the inheritance of F4ab and F4ac receptors might be under the control of two closely linked loci.  相似文献   

18.
Fu WX  Liu Y  Lu X  Niu XY  Ding XD  Liu JF  Zhang Q 《PloS one》2012,7(3):e32127
Enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbria is the major pathogenic bacteria causing diarrhoea in neonatal and post-weaning piglets. Previous studies have revealed that the susceptibility to ETEC F4ab/F4ac is an autosomal Mendelian dominant trait and the loci controlling the F4ab/F4ac receptor are located on SSC13q41, between markers SW207 and S0283. To pinpoint these loci and further validate previous findings, we performed a genome-wide association study (GWAS) using a two generation family-based population, consisting of 301 piglets with phenotypes of susceptibility to ETEC F4ab/F4ac by the vitro adhesion test. The DNA of all piglets and their parents was genotyped using the Illumina PorcineSNP60 BeadChip, and 50,972 and 50,483 SNPs were available for F4ab and F4ac susceptibility, respectively, in the association analysis after quality control. In summary, 28 and 18 significant SNPs (p<0.05) were detected associated with F4ab and F4ac susceptibility respectively at genome-wide significance level. From these significant findings, two novel candidate genes, HEG1 and ITGB5, were firstly identified as the most promising genes underlying F4ab/F4ac susceptibility in swine according to their functions and positions. Our findings herein provide a novel evidence for unravelling genetic mechanism of diarrhoea risk in piglets.  相似文献   

19.
20.
F4 enterotoxigenic Escherichia coli (F4 ETEC) are an important cause of diarrhea in neonatal and newly-weaned pigs. Based on the predicted differential O-glycosylation patterns of the 2 MUC13 variants (MUC13A and MUC13B) in F4ac ETEC susceptible and F4ac ETEC resistant pigs, the MUC13 gene was recently proposed as the causal gene for F4ac ETEC susceptibility. Because the absence of MUC13 on Western blot from brush border membrane vesicles of F4ab/acR+ pigs and the absence of F4ac attachment to immunoprecipitated MUC13 could not support this hypothesis, a new GWAS study was performed using 52 non-adhesive and 68 strong adhesive pigs for F4ab/ac ETEC originating from 5 Belgian farms. A refined candidate region (chr13: 144,810,100–144,993,222) for F4ab/ac ETEC susceptibility was identified with MUC13 adjacent to the distal part of the region. This candidate region lacks annotated genes and contains a sequence gap based on the sequence of the porcine GenomeBuild 10.2. We hypothesize that a porcine orphan gene or trans-acting element present in the identified candidate region has an effect on the glycosylation of F4 binding proteins and therefore determines the F4ab/ac ETEC susceptibility in pigs.  相似文献   

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