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At least 937 records · Page 52Linked to original sources
PubMed2006

[HLA-A, B, DRB1 gene polymorphism of Beijing population was studied by high-resolution polymerase chain reaction sequence-based typing].

OBJECTIVE: To investigate the gene polymorphism of human leukocyte antigen (HLA)-A, B, DRB1 loci in the population of Beijing region, and research on the application feasibility of polymerase chain reaction sequence-based typing (PCR-SBT) method. METHODS: PCR-SBT method was applied to determine HLA- A, B, DRB1 genotypes of 618 unrelated healthy individuals of Beijing region. RESULTS: A total of 84 different alleles and 199 genotypes of HLA-A, 143 alleles and 366 genotypes of HLA-B, 122 alleles and 286 genotypes of HLA-DRB1 were detected. CONCLUSION: The results showed the characteristics of HLA-A, B, DRB1 distributions, and provided more comprehensive and accurate gene data that may serve as normal reference values for all of Beijing people.

Asian People↗
PubMed1989

Restriction fragment polymorphisms of the HLA-DR, HLA-DQ, and insulin gene regions in IDDM: the GAW5 data.

The primary aim of the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5) was to collect and analyze new data on DNA polymorphisms closely linked to the HLA-D region and the insulin gene. The probes and restriction enzymes described here were used by all ten participating labs, and the data from Southern blotting were interpreted and reported according to conventions developed for the Workshop. These DNA data on members of 94 families with two or more IDDM sibs constitute the largest such sample available. The data were used in most of the analyses presented at the Workshop meeting, and are available on request.

Chromosome Mapping↗
PubMedDate not supplied

[Genetic and immunologic aspects of type 1 diabetes mellitus].

Prediction of type 1 diabetes mellitus (IDDM) and its identification in preclinical period is one of the central problems in modern medicine. They are based comprehensive genetic, immunologic and metabolic evaluations. We observed four hundred seven first-degree relatives of patients with IDDM (240 families in which one of the children or one of the parents had IDDM) have been included in the study. The study of HLA-DQA1, HLA-DQB1 polymorphic alleles and DRB1 genes and their combinations. The genetic study included searching HLA loci (HLA-DQA1, HLA-DQB1 polymorphic alleles and DRB1 genes) loci. To evaluate the genetic risk two approaches we used: first--carrying predisposing HLA-DQ alleles and DRB1-genes and it's combination (mainly associated in Russian population was DRB1*04-DQB1*0302, DRB1*04-DQA1*0301, DQA1*0301-DQB1*0302, DQA1*0301-DQB1*0302 and four susceptible alleles in A- and B- chains (Asp 57-, Arg 52+)) and second--IBD (identity by descent), in Russian population HLA-identical for 2 haplotypes sibs had risk of development of IDDM of 18%, for 1 haplotype--3%, for 0 haplotype-0.9%. The antibodies (ICA, IAA) prevalence rate has not depended on availability of predisposing HLA-DQ alleles and DRB1-genes and haploidentity of normal sibs and sibs with IDDM. However, GADA prevalence rate in groups having high predisposed alleles has been noticed as significantly higher (28.6%) comparing with 7.7% in groups that had no predisposing alleles (p < 0.05). The comparison of antibodies prevalence rate to sibs HLA-identity has shown the significant increase or GADA prevalence rate in group of siblings identical for one haplotype comparing with non-identical sibs (27.3% and 0% respectively, p < 0.001).

Alleles↗
PubMed1980

HLA-DR antigens have polymorphic light chains and invariant heavy chains as assessed by lysine-containing tryptic peptide analysis.

HLA-DR antigens were isolated from B lymphoblastoid cells labeled with either [3H]- or [14C]lysine. Double-label comparisons of the tryptic peptides by microbore ion-exchange chromatography led to the following conclusions: The heavy and light chains share few peptides, one of which is free lysine that is liberated from the polypeptide chains by trypsin. The heavy chains of different HLA-DR allospecificities are virtually identical in all cell lines examined. In contrast, the light chains of different HLA-DR allospecificities are nonidentical and, thus, must bear the alloantigenic determinant.

B-Lymphocytes↗
PubMed1996

Single-strand conformation polymorphism (SSCP) analysis of HLA-DRB1*1101-06.

Single-strand conformation polymorphism (SSCP) has been developed as a method for detecting the presence of mutations in a segment of DNA. We applied it to the subtyping of the DR11 group of alleles. The SSCP patterns of DRB1-DR52 group-specific products were defined in cell lines representing the DRB1*1101-06 alleles, using non-denaturing acrylamide gel electrophoresis and silver staining. Only one set of gel electrophoresis conditions was able to discriminate the DR11 alleles tested. The protocol was validated in an analysis of 105 DR11-positive individuals previously typed by oligonucleotides probing. The study demonstrates the suitability of the SSCP technique to define the DRB1*1101-06 alleles, the technique being particularly valuable in confirming and extending the oligotyping of DRB1-DR52 heterozygous samples.

Cell Line↗
PubMed1998

Microsatellite single nucleotide polymorphisms in the HLA-DQ region.

Sequencing studies were performed in three previously described microsatellite and minisatellite markers located within the HLA-DQ region, DQCAR, DQCARII and G51152. Multiple nucleotide substitutions that did not change size polymorphisms were observed in all three markers. In all loci, the number of core repeats did not correlate with neighboring DQ allele sequence motifs while single nucleotide changes within or flanking the microsatellite sequence did. This result indicates higher mutation rates for microsatellite expansions/contractions than for nucleotide substitutions in these loci. Further analysis indicated an almost complete phylogenetic correspondence between DQCAR single nucleotide polymorphisms (SNPs) and DQB1 sequences on one side (1.0-1.5 kb apart) and a complete relationship between DQCARII and DQA1 sequences on the other (4.5 kb apart). In contrast, G51152 sequences did not correspond perfectly with DQB1 allelic sequences, thus suggesting the existence of several ancestral crossovers between this marker and DQB1 (20-25 kb). Sequencing microsatellites might be useful in disease mapping studies by increasing marker informativeness and by helping in the interpretation of association study results. It is also proposed that SNPs within the flanking region of CA repeats could be used to develop biallelic markers from already available mapped microsatellite markers.

Alleles↗
PubMed2002

HLA-DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica.

Genetic susceptibility to type 1 diabetes is determined by a combination of HLA-DQ and DRB1 alleles. In the present study, HLA associations with type 1 diabetes were investigated in the Jamaican population. DRB1 and DQ genotyping was performed on 45 type 1 diabetic patients and 132 control subjects born and resident in Jamaica. The small number of patients available for study reflected the low prevalence of type 1 diabetes in Jamaica. The results were compared with those from other African heritage populations and white Caucasians. The highest relative risk was associated with the DRB1*03-DQ2/DRB1*04-DQ8 genotype. Both DRB1*0401-DQ8 and DRB1*0408-DQ8 were positively associated with disease. DRB1*0408-DQ8 is uncommon amongst white Caucasians, where DRB1*0401-DQ8 is the major predisposing haplotype. The DRB1*1503-DQ6 haplotype was associated with protection from diabetes in the Jamaican population. This haplotype is rare amongst white Caucasians, where DRB1*1501-DQ6 is the protective haplotype. Data from African heritage populations suggest that DRB1*1503-DQ6 might be less protective than DRB1*1501-DQ6. DRB1*03-DQA1*0401-DQB1*0402 was associated with protection from diabetes in the Jamaican population, whereas in white Caucasians DRB1*08-DQA1*0401-DQB1*0402 is predisposing. These data demonstrate that comparison of genetic associations with type 1 diabetes in races with population-specific DRB1-DQ haplotypes provides new information as to the exact determinants of disease susceptibility. Further support is provided for roles of the DQ genes and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining susceptibility to type 1 diabetes.

Adult↗
PubMed2000

Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1).

Antigenic polymorphism and HLA restriction may limit the immunogenicity of a subunit vaccine against liver-stage Plasmodium falciparum. We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN-gamma responses in residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24, -B13, and -B40 are the most common class I alleles. LSA-1 polymorphism was limited to a single non-synonymous mutation encoding serine (S), proline (P), or threonine (T) at amino acid 85. Nine-mer 84-92 peptides with S, T, or P at the primary anchor position bound differentially to HLA-A11, -A2, and -B7. IFN-gamma ELISPOT responses increased with age in malaria-exposed subjects: 14-16% and 30-36% of 2-5- and 6-54-year-olds, respectively, had > or =10 IFN-gamma-secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P<0.05). IFN-gamma responses to all three peptides were also greater for older than younger individuals. No children < 3 years old had lymphocytes that responded to all three 84-92 peptides, whereas 45% of adults (mean age 48 years) had aggregated IFN-gamma responses. These data support the notion that age-related cumulative exposure to P. falciparum increases the frequency of IFN-gamma responses to polymorphic epitopes of liver-stage antigens such as LSA-1.

Adolescent↗
PubMed1997

Effect of polymorphism of the HLA-DPA1 chain on presentation of antigenic peptides.

Human T-cell clones that recognize a peptide from mycobacterial heat shock protein 60 in the context of HLA-DP were found to be sensitive to changes in the DPA1 chain of the restricting element, optimal responses being seen with the combination HLA-DPA1*0201 and HLA-DPB*0301. HLA-DP dimers containing HLA-DPA1*01 were only able to present antigenic peptides to T-cell clones when peptides were present throughout the period of coculture of T cells with antigen presenting cells. In contrast the optimal HLA-DP dimer could also stimulate T-cell clones maximally when incubated with peptides for 1 h and then thoroughly washed. This suggests that the DPA1 polymorphism influenced the strength of binding of antigenic peptides to the HLA-DP dimer. Modeling studies identified amino acid 31 of DPA1 as the polymorphic residue most likely to account for this effect. This is the first demonstration that the relatively limited polymorphism displayed by DPA1 has functional consequences.

Amino Acid Sequence↗
PubMed1988

Analysis of HLA-DP allelic sequence polymorphism using the in vitro enzymatic DNA amplification of DP-alpha and DP-beta loci.

Allelic sequence variation of the HLA DP-alpha and DP-beta genes has been analyzed in a panel of 34 DP-typed cell lines. The polymorphic second exon of these genes was specifically amplified in vitro by the polymerase chain reaction method, using the thermostable DNA polymerase of Thermus, aquaticus. The analysis of M13 clones containing the amplified DP-beta sequences revealed a total of 14 allelic variants. In general, specific allelic DP-beta sequences were associated with each of the defined DPw1-w6 types, with beta allele subtypes revealed for the DPw2 and DPw4 specificities. An additional six DP-beta alleles which did not correlate with any of the T cell-defined specificities (DP "blanks") were also identified. Only the two previously characterized alleles of DP-alpha were detected. These observations suggest that the T cell-defined DP specificities are determined by polymorphic residues on the beta-chain. The sequence polymorphisms in DP-beta are clustered in a few specific regions, and can be detected using sequence-specific oligonucleotide probes and polymerase chain reaction amplified DNA in a rapid dot-blot format. This approach provides a simple and informative method of DP typing. The DP-beta sequences derived from four DP-typed celiac disease patients were compared with the distribution of DP-beta alleles in control individuals.

Alleles↗
PubMed1997

Isolation of scFv fragments to polymorphic and monomorphic HLA-DR epitopes from a synthetic phage library.

The possibility of producing human recombinant antibodies by the phage display libraries technology has opened up new perspectives in the fields of immunological research and therapeutic applications. Despite the interest for a potential use of this technology in the HLA field, no information is so far available about selection and screening of libraries with HLA antigens. In this study we report our first experience with expression and characterization of human single-chain antibody fragments (scFvs) against HLA-DR epitopes selected from a synthetic phage library.

Bacteriophages↗
PubMed1992

Restriction fragment length polymorphism analysis of HLA-DR- and DQ-linked alleles in multiple sclerosis in Spain.

HLA-DR allele subtypes in multiple sclerosis (MS) individuals in Spain were determined by restriction fragment length polymorphism (RFLP) analysis. The well-established association of DRw15, DQw6, Dw2 alleles and MS susceptibility was confirmed. The strength of its association, however, was relatively weak in our MS population and no involvement with any other DR allele was observed. DQw6 increase correlated with the elevation of the involved DR2 subtype. The hypothesis that MS-associated susceptibility genes may be more closely associated with the DQ than the DR region was not supported by our findings which, on the other hand, could be in concordance with the concept that multiple genes contribute to MS susceptibility.

Alleles↗
PubMed1983

Biochemical analysis of the polymorphism of three HLA-D region antigens.

Two-dimensional gel electrophoretic analyses of immunoprecipitates of the HLA-D region antigens revealed three beta (Mr 28 X 10(3) to 30 X 10(3) structurally polymorphic polypeptides. Analyses of the nonglycosylated beta polypeptides indicated that their polymorphism is most probably due to variations in amino acid structure. The polymorphism has been examined using lymphoblastoid cell lines that were derived from different geographical populations (North European and Italian) and that expressed various HLA-DR alloantigenic specificities. The results confirm that the positional variation of one beta polypeptide (namely beta-1) correlated with the HLA-DR allospecificity and was not influenced by the ethnic origin of the individual donating the cells. The positional variation of a second beta polypeptide (namely beta-2) was consistent with strong linkage dis-equilibrium between the corresponding genetic locus and the HLA-DR locus. Further, the association with a particular HLA-DR allospecificity was population-dependent; that is, different beta-2 polypeptides were associated with the same HLA-DR specificity in different geographical populations. In contrast, the position of the third beta polypeptide (namely, beta-3) which corresponds to the HLA-DC locus, did not necessarily vary with the HLA-DR specificity; that is, apparently the same beta-3 polypeptide was associated with different HLA-DR specificities provided the cells were of the same ethnic origin. The data indicate that lymphoblastoid cells express at least three sets of HLA-D region antigens that are encoded by different loci including HLA-DR and DC.

Antibodies, Monoclonal↗
PubMed2002

HLA and cytokine gene polymorphisms in biliary atresia.

BACKGROUND/AIMS: Extrahepatic biliary atresia remains one of the major hepatic causes of death in early childhood. Though a number of hypotheses have been developed to account for this disease, its aetiopathogenesis is poorly understood. One possibility is that this is an immune mediated disease which occurs following either toxic or infectious insult in a genetically susceptible host. Earlier studies suggested weak HLA associations but these remain unconfirmed. More recently studies of viral and autoimmune liver disease have begun to investigate non-MHC immunoregulatory gene polymorphisms. METHODS: In the present study we used molecular genotyping to investigate selected HLA A, B, DRB1, DQA1, DQB1 and DPB1 alleles as well as polymorphisms in the interleukin-1 gene family, interleukin-10 promoter sequence and tumour necrosis factor alpha promoter genes in 101 children referred for surgical assessment with extra hepatic biliary atresia. Genotyping data were compared with those of 134 racially and geographically matched healthy adult health care workers. RESULTS AND CONCLUSIONS: Overall there were no statistically significant differences in the distribution of any of the genes tested comparing patients and controls. These data suggest that biliary atresia is not an HLA-associated disease and that polymorphisms in both the interleukin-1 and interleukin-10 genes are not risk factors for this disease.

Adult↗
PubMed1998

Differential expression and regulation of a human transgene, HLA-B27, in mouse placental and embryonic cell lines.

Unlike other somatic cells, human placental trophoblast cells do not express the highly polymorphic HLA-A and HLA-B human leukocyte major histocompatibility antigens that would stimulate maternal immunological rejection of the fetus. To investigate mechanisms underlying cell lineage-specific expression, cell lines were generated from homozygous matings of HLA-B27 transgenic mice. Trophoblast cell lines were generated from gestation day 10 placentas and fibroblasts were cultured from gestation day 13/14 embryos. Polymerase chain reaction (PCR) readily identified HLA-B DNA in transgenic trophoblastic cells but specific mRNA was of low abundance, being detectable by reverse transcriptase PCR but not by Northern blot hybridization. HLA-B-specific protein in/on the trophoblast cells was undetectable by cell enzyme-linked immunosorbent assay and the protein was not induced by exposing the trophoblastic cells to interferon-gamma (IFN-gamma). Restricted expression was specific for the HLA-B transgene and its antigen; IFN-gamma-inducible endogenous H-2Db class I antigens were detectable on the trophoblast cells. In contrast to the trophoblastic cells, HLA-B27 transgenic fibroblasts expressed IFN-gamma-inducible HLA class I antigens as well as H-2Db antigens. Thus, the mechanism(s) regulating expression of the polymorphic HLA-B antigen in trophoblastic cells is gene-specific, IFN-gamma-resistant and operative at the level of transcription or immediate post-transcription.

Animals↗
PubMed1988

DNA polymorphism of the HLA-B35 gene associated to different HLA-C locus alleles.

Peripheral blood leukocyte DNA from 31 donors, previously typed as HLA-B35, was digested with EcoRV and analyzed by Southern transfer and hybridization to an HLA class I probe. Out of 31 HLA-B35 positive (+) individuals, 24 showed a 4.6-kb band, previously associated with the B35 allele by Cohen et al. (Proc Natl Acad Sci USA 80:6289-6292). The HLA-B35 allele has a strong linkage disequilibrium (70%) with the Cw4 allele. All samples having the 4.6-kb band corresponded to HLA-B35+, Cw4+ cells, whereas those lacking the band came from HLA-B35+, Cw4-negative (-) cells. Five HLA-B35-, Cw4+ samples were also studied and none showed the band. An HLA-B locus-specific probe gave a strong hybridization signal to this fragment, whereas an HLA-C locus-specific probe revealed different bands. The results suggest that the 4.6-kb fragment contains the B35 gene. Digestion with other restriction enzymes, located the polymorphic site to the 3' end of the gene. Analysis of 18 additional individuals with other specificities of the "4c" antigenic cluster (HLA-B18, B51, B52 and B53) showed that the EcoRV/4.6 kb-band was also present in 5/5 B52 cells and 4/4 B53 samples.

Alleles↗