Dataset Information

MHC-DRB1/DQB1 Gene Polymorphism and Its Association with Resistance/Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep.

ABSTRACT: The aim of this study was to analyze the relationship between polymorphism of the MHC-DRB1/DQB1 gene and its resistance to Cystic Echinococcosis (C.E), as well as to screen out the molecular genetic marker of antiechinococcosis in Chinese Merino sheep. The MHCII-DRB1/DQB1 exon 2 was amplified by polymerase chain reaction (PCR) from DNA samples of healthy and hydatidosis sheep. PCR products were characterized by restriction fragment length polymorphism (RFLP) technique. Five restriction enzymes (Mval, HaeIII, SacI, SacII, and Hin1I) were employed to cut DRB1, while seven restriction enzymes (MroxI, ScaI, SacII, NciI, TaqI, Mval, and HaeIII) were employed to cut DQB1.Results showed that frequencies of patterns Mvalbb (P < 0.01), SacIab in DRB1 exon 2 (P < 0.05), and TaqIaa, HaeIIInn (P < 0.01) in DQB1 exon 2 were significantly higher in the healthy group compared with the C.E individuals, which implied that there was a strong association between these genotypes and hydatidosis resistance or susceptibility. Chi-square test showed that individuals with the genic haplotype DRB1-SacIab/DRB1-Mvalbb/DQB1-TaqIaa/DQB1-HaeIIInn (P < 0.01) were relatively resistant to C.E, while individuals with the genic haplotypes DRB1-Mvalbc/DQB1-Mvalyy/DQB1-TaqIab/DQB1-HaeIIImn (P < 0.01) and DRB1-Mvalbb/DQB1-Mvalcc/DQB1-TaqIab/DQB1-HaeIIImn (P < 0.01) were more susceptible to C.E. In addition, to confirm these results, a fielding experiment was performed with Chinese Merino sheep which were artificially infected with E.g. The result was in accordance with the results of the first study. In conclusion, MHC-DRB1/DQB1 exon 2 plays an important role as resistant to C.E in Chinese Merino sheep. In addition, the molecular genetic marker of antiechinococcosis (DRB1-SacIab/DRB1-Mvalbb/DQB1-TaqIaa/DQB1-HaeIIInn) was screened out in Chinese Merino sheep.

SUBMITTER: Shen H

PROVIDER: S-EPMC3982463 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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MHC-DRB1/DQB1 Gene Polymorphism and Its Association with Resistance/Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep.

Shen Hong H Han Guohua G Jia Bin B Jiang Song S Du Yingchun Y

Journal of parasitology research 20140324

The aim of this study was to analyze the relationship between polymorphism of the MHC-DRB1/DQB1 gene and its resistance to Cystic Echinococcosis (C.E), as well as to screen out the molecular genetic marker of antiechinococcosis in Chinese Merino sheep. The MHCII-DRB1/DQB1 exon 2 was amplified by polymerase chain reaction (PCR) from DNA samples of healthy and hydatidosis sheep. PCR products were characterized by restriction fragment length polymorphism (RFLP) technique. Five restriction enzymes ( ...[more]

PMID: 24782918

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Project description:Cystic echinococcosis (CE), one of the world's most geographically widespread diseases, still represents a considerable economic and public health significance, although a variety of methods has been used to control the disease. It has been demonstrated that genetic factors, especially variations in MHC loci, can influence the outcome of CE infection in the human population. The study described here was designed to determine whether variation in MHC-DQB1 was associated with susceptibility or resistance to CE in sheep. If so, it would lay a theoretical foundation for breeding disease resistance sheep in future. This study was carried out on 204 Chinese Merino sheep, including 101 CE sheep and 103 healthy controls. The polymorphism of MHC-DQB1 exon 2 was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and x (2) test was used to compare genotype frequencies between CE sheep and healthy controls. A total of 22 alleles and 42 genotypes were identified in DQB1 exon 2 in Chinese Merino sheep. In addition, x (2) test showed that frequencies of DQB1-TaqIaa and DQB1-HaeIIInn genotypes were significantly higher in the healthy group (82.5% and 57.3%, respectively) than that in the CE group (57.4% and 28.9%, respectively) (both p values = 0, OR = 0.286, 0.303, respectively), suggesting that these genotypes appeared to be associated with resistance to CE. Whereas, frequencies of DQB1-TaqIab and DQB1-HaeIIImn genotypes were significantly higher in the CE group (36.9% and 32.0%, respectively), as compared with the healthy group (16.5% and 11.15%, respectively) (p = 0.001, 0.001 and OR = 2.963, 3.629, respectively), indicating that these genotypes might be associated with susceptibility to CE. It is concluded that the genetic polymorphism within MHC-DQB1 might influence immune responses to pathogens, thus leading to the development of CE or protection against CE in Chinese Merino sheep, which would pave the way for breeding disease resistance sheep in future.

Project description:INTRODUCTION: Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients' genotypic risk of developing MS. METHODS AND RESULTS: A transmission disequilibrium test (TDT) of the DRB1*-DQB1* haplotypes in 943 trio families, confirmed a higher than expected transmission rate (over-transmission) of the *13:03-*03:01 (OR = 2.9, P = 7.6×10(-3)), *04:05-*03:01 (OR = 2.4, P = 4.4×10(-6)) and *03:01-*02:01 (OR = 2.1, P = 1.0×10(-15)) haplotype. In contrast, the *16:01-*05:02 (OR = 0.5, P = 5.4×10(-11)) and the *15:02-*06:01 (OR = 0.3, P = 1.5×10(-3)) haplotypes exhibited a lower than expected transmission rate (under-transmission). The independence of the transmission of each positively and negatively associated haplotype was confirmed relative to all positively associated haplotypes, and to the negatively associated *16:01-*05:02 haplotype. In patients, carriage of two predisposing haplotypes, or of protective haplotypes, respectively increased or decreased the patient's risk of developing MS. The risk of MS followed a multiplicative model of genotypes, which was, in order of decreasing ORs: *04:05-*0301/*03:01-*02:01 (OR = 4.5); *03:01-*02:01/*03:01-*02:01 (OR = 4.1); and the *16:01-*05:02/*16:01-*0502 (OR = 0.2) genotypes. Analysis of DRB1 and DQB1 protein chain residues showed that the Val/Gly residue at position 86 of the DRB1 chain was the only difference between the protective *16:01- *15:02 alleles and the predisposing *15:01 one. Similarly, the Ala/Val residue at position 38 of the DQB1 chain differentiated the positively associated *06:02 allele and the negatively associated *05:02, *06:01 alleles. CONCLUSIONS: These findings show that the association of specific, independent DRB1*-DQB1* haplotypes confers susceptibility or resistance to MS in the MS-prone Sardinian population. The data also supports a functional role for specific residues of the DRB1 and DQB1 proteins in predisposing patients to MS.

Project description:Multiple sclerosis (MS), a common central nervous system inflammatory disease, has a major heritable component. Susceptibility is associated with the MHC class II region, especially HLA-DRB5*0101-HLA-DRB1*1501-HLA-DQA1*0102-HLA-DQB1*0602 haplotypes(hereafter DR2), which dominate genetic contribution to MS risk. Marked linkage disequilibrium (LD) among these loci makes identification of a specific locus difficult. The once-leading candidate, HLA-DRB1*15, localizes to risk, neutral, and protective haplotypes. HLA-DRB1*15 and HLA-DQB1*0602, nearly always located together on a small ancestral chromosome segment, are strongly MS-associated. One intervening allele on this haplotype, viz. HLA-DQA1*0102, shows no primary MS association. Two Canadian cohorts (n = 830 and n = 438 trios) genotyped for HLA-DRB1, HLA-DQA1 and HLA-DQB1 alleles were tested for association using TDT. To evaluate epistasis involving HLA-DRB1*15, transmissions from HLA-DRB1*15-negative parents were stratified by the presence/absence of HLA-DRB1*15 in affected offspring. All 3 alleles contribute to MS susceptibility through novel epistatic interactions. HLA-DQA1*0102 increased disease risk when combined with HLA-DRB1*1501 in trans, thereby unambiguously implicating HLA-DQ in MS susceptibility. Three-locus haplotypes demonstrated that HLA-DRB1*1501 and HLA-DQB1*0602 each influence risk. Transmissions of rare morcellated DR2 haplotypes showed no interaction with HLA-DQA1*0102. Incomplete haplotypes bearing only HLA-DRB1*1501 or HLA-DQB1*0602 did not predispose to MS. Balanced reciprocal transmission distortion can mask epistatic allelic association. These findings implicate epistasis among HLA class II alleles in human immune responses generally, provide partial explanation for intense linkage disequilibrium in the MHC, have relevance to animal models, and demonstrate key roles for DR2-specific interactions in MS susceptibility. MHC disease associations may be more generally haplotypic or diplotypic.

Project description:BackgroundCystic Echinococcosis (CE), caused by infection with the Echinococcus granulosus (E. granulosus), represents considerable health problems in both humans and livestock. Nevertheless, the genetic program that regulates the host response to E. granulosus infection is largely unknown. Previously, using microarray analysis, we found that the innate immunity played a vital role in the E. granulosus defense of the intestine tissue where E. granulosus first invaded. Subsequently, we turned our attention to investigating the molecular immune mechanism in its organ target, the liver, which is where the E. granulosus metacestodes are established and live for very long periods. In this work, the microarray-based methodology was used to study gene expression profiles in the liver of sheep infected with E. granulosus at 8 weeks post infection, corresponding to the early cystic established phase.MethodsA total of 6 female-1-year-old healthy Kazakh sheep were used for the experiments. Three Kazakh sheep were orally infected with E. granulosus eggs, and the others remained untreated and served as controls. Sheep were humanely euthanized and necropsized at 8 weeks post-infection (the early stage of cyst established). The microarray was used to detect differential hepatic gene expression between CE infection sheep and healthy controls at this time point. Real-time PCR was used to validate the microarray data.ResultsWe found that E. granulosus infection induces 153 differentially expressed genes in the livers of infected sheep compared with healthy controls. Among them, 87 genes were up-regulated, and 66 genes were notably down-regulated. Functional analysis showed that these genes were associated with three major functional categories: (a) metabolism, (b) the immune system and (c) signaling and transport. Deeper analysis indicated that complement together with other genes associated with metabolism, played important roles in the defense of E. granulosus infection.ConclusionThe present study identified genes profiling in the liver tissue of E. granulosus infection in sheep. The expression pattern obtained here could be helpful for understanding the molecular immunity mechanisms of host responses to E. granulosus infection. However, it is necessary to carry out further studies to evalute the role of these genes.

Project description:Genetic variation among sheep breeds in resistance to gastrointestinal nematodes (GIN) has been demonstrated in several production environments. Relationships between the ovine major histocompatibility complex and resistance to GIN have been studied, but few studies have systematically examined this issue in less-developed and semi-arid regions. The aim of the current study was to explore associations between fecal worm egg counts (FEC) for several GIN and polymorphisms in the DRB1 gene. One hundred male lambs were selected at 4-6 months of age from weaned animals in five flocks (n = 20 per flock). Body weights were determined, FAMACHA scores based on color of the ocular mucous membranes were assigned as an indicator of anemia, and blood and fecal samples were collected twice to evaluate FEC and blood packed cell volume (PCV) and for DNA isolation. A repeated-measures analysis of variance was used to test effects of genotype on FEC. The model included fixed effects of flock, genotype, time of measurement (1 or 2), and flock × time and genoype × time interactions, and a random (repeated) effect of lamb. Two genotypes (A1A1 and A1A2) were observed following digestion of Region 1 of Ovar-DRB1 with PstI. Genotypic frequencies were 0.73 for A1A1 and 0.27 for A1A2. FEC differed between Ovar_DRB1 genotypes A1A1 and A1A2 for Marshallagia marshalli, Strongyle, and total nematode FEC. Observed FEC were 30-41% lower for genotype A1A1. Differences among genotypes were consistent across measurement times, with no effect of genotype × measurement time interaction for any parasite class (P ≥ 0.34). A significant association was observed between FAMACHA scores and lamb PCV, and the residual correlation between these two variables was -0.51 (P < 0.001). FAMACHA scores can thus be used to detect differences among lambs in PCV, and polymorphic markers of Ovar-DRB1 have potential value as an indicator of parasite resistance in applied animal breeding programs on sheep farms in this region.

Project description:BackgroundMerino and Merino-derived sheep breeds have been widely distributed across the world, both as purebred and admixed populations. They represent an economically and historically important genetic resource which over time has been used as the basis for the development of new breeds. In order to examine the genetic influence of Merino in the context of a global collection of domestic sheep breeds, we analyzed genotype data that were obtained with the OvineSNP50 BeadChip (Illumina) for 671 individuals from 37 populations, including a subset of breeds from the Sheep HapMap dataset.ResultsBased on a multi-dimensional scaling analysis, we highlighted four main clusters in this dataset, which corresponded to wild sheep, mouflon, primitive North European breeds and modern sheep (including Merino), respectively. The neighbor-network analysis further differentiated North-European and Mediterranean domestic breeds, with subclusters of Merino and Merino-derived breeds, other Spanish breeds and other Italian breeds. Model-based clustering, migration analysis and haplotype sharing indicated that genetic exchange occurred between archaic populations and also that a more recent Merino-mediated gene flow to several Merino-derived populations around the world took place. The close relationship between Spanish Merino and other Spanish breeds was consistent with an Iberian origin for the Merino breed, with possible earlier contributions from other Mediterranean stocks. The Merino populations from Australia, New Zealand and China were clearly separated from their European ancestors. We observed a genetic substructuring in the Spanish Merino population, which reflects recent herd management practices.ConclusionsOur data suggest that intensive gene flow, founder effects and geographic isolation are the main factors that determined the genetic makeup of current Merino and Merino-derived breeds. To explain how the current Merino and Merino-derived breeds were obtained, we propose a scenario that includes several consecutive migrations of sheep populations that may serve as working hypotheses for subsequent studies.

Project description:BACKGROUND: Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102-DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS. METHODS: The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II(-/-)), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile. RESULTS: PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice. CONCLUSIONS: While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.

Dataset Information

MHC-DRB1/DQB1 Gene Polymorphism and Its Association with Resistance/Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep.

Publications

MHC-DRB1/DQB1 Gene Polymorphism and Its Association with Resistance/Susceptibility to Cystic Echinococcosis in Chinese Merino Sheep.

Similar Datasets

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