SEARCH · PubMed Health

Results for “HLA polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed1996

HLA DR and DQ polymorphism in Ashkenazi and non-Ashkenazi Jews: comparison with other Mediterraneans.

HLA-DR and DQ alleles have been detected by DNA typing in Ashkenazi and non-Ashkenazi Jews from Israel. Allele frequencies, characteristic DR/DQ linkage disequilibria, population distances and their corresponding dendrogram by using the Neighbor-Joining method were used to study relatedness between Jewish and other Mediterranean and non Mediterranean populations. Closest relatedness is observed between Ashkenazi and non-Ashkenazi Jews, and, in decreasing order, also with Algerians, Spaniards (including Spanish-Basques), French and Italians. Also, particular characteristic Central European alleles are observed in Ashkenazi Jews and Mediterranean/African alleles in non-Ashkenazi Jews. This is consistent with historical data, Jews being an ancient Mediterranean population, who have had a certain degree of admixture with their 2000-3000 years old neighbors in spite of cultural and religious traditions which have preserved identity outside Israel.

Algeria↗

PubMed2006

HLA class II DRB1 polymorphism in Argentinians undergoing chronic Trypanosoma cruzi infection.

DNA typing of human lymphocyte antigen (HLA)-dicloro-1-[beta]-D-ribofuranosyl-benzimidazole 1 (DRB1) alleles in 35 individuals serologically positive for T. cruzi and in 41 healthy controls was performed. DRB1*0409 allele was significantly more prevalent in seropositive individuals, with a trend being also observed for the DRB1*0701 and DRB1*1503 alleles. Although statistically insignificant, the latter was found more frequent in cases with cardiomyopathy.

Animals↗

PubMed1999

Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism.

Herein, we review the epitope approach to vaccine development, and discuss how knowledge of HLA supertypes might be used as a tool in the development of such vaccines. After reviewing the main structural features of the A2-, A3-, B7-, and B44- supertype alleles, and biological data demonstrating their immunological relevance, we analyze the frequency at which these supertype alleles are expressed in various ethnicities and discuss the relevance of those observations to vaccine development. Next, the existence of five new supertypes (A1, A24, B27, B58, and B62) is reported. As a result, it is possible to account for the predominance of all known HLA class I with only nine main functional binding specificities. The practical implications of this finding, as well as its relevance to understanding the functional implication of MHC polymorphism in humans, are discussed.

Alleles↗

PubMed1996

Population genetic studies of HLA-G: allele frequencies and linkage disequilibrium with HLA-A1.

HLA-G is a class I gene that is expressed in the extravillous cytotrophoblast. Although the function of this gene is still unknown, its expression at the maternal-fetal interface suggests that HLA-G may play a key role in the induction of tolerance during pregnancy. Preliminary to our studies of the effects of HLA-G polymorphisms on pregnancy outcome, we have defined HLA-G alleles in the Hutterites. We report here the presence of nine HLA-G alleles that differ with respect to nucleotide sequences, including four groups of alleles that differ with respect to amino acid sequences, and striking linkage disequilibrium between HLA-G and HLA-A alleles. The levels and sites of polymorphism in HLA-G suggest that this gene had a unique evolutionary history and may perform nonclassical functions at the maternal-fetal interface.

Adult↗

PubMed2004

Polymorphism analysis within the HLA-A locus by universal oligonucleotide array.

Human leukocyte antigen (HLA) class I genes present some of the most complex single nucleotide polymorphism (SNP) patterns in the human genome. HLA typing is therefore extremely challenging. In this article, we use the ligation detection reaction (LDR) combined with a universal array (UA) as a robust and efficient method to analyze SNPs within the HLA-A region that includes HLA-A alleles of interest for immunotherapy in tumor diseases. The LDR, combined with a UA platform, has been optimized for the detection of 27 alleles distributed within exons 2 and 3 of HLA-A. The assay involves the amplification by PCR of the HLA-A genomic region (1,900 bp), the cycled ligation reaction, followed by the capture of ligated products through hybridization onto a UA. Each slide was designed to allow the detection of up to eight samples in parallel. The PCR/LDR/UA HLA-A assay was evaluated by analyzing 62 individuals (31 homozygous and 31 heterozygous) previously typed by direct sequencing. We demonstrate that the microarray genotyping procedure described here is a robust and efficient method for unambiguous detection of HLA alleles. HLA genotyping by PCR/LDR/UA is in perfect agreement with typing obtained by direct sequencing. Our results clearly demonstrate that the combination of enzymatic processing (LDR) and a demultiplexing hybridization onto a UA is a robust tool for SNP discrimination within the highly polymorphic HLA region. We demonstrate the specificity and efficiency of such an approach, suggesting the feasibility of a PCR/LDR/UA low resolution HLA typing procedure.

Alleles↗

PubMed1988

Low degree of DNA polymorphism in the HLA-linked lymphotoxin (tumour necrosis factor beta) gene.

Tumour necrosis factors (TNF) alpha (cachectin) and beta (lymphotoxin) are lymphokines with many biological activities. For example, the molecules regulate the immune system, which is of special interest since the genes for the TNF are located within the human major histocompatibility complex (MHC). The MHC encodes HLA-molecules that play a critical role in the cellular interactions of the immune response. To test whether genetic polymorphism in the TNF genes may be involved in the associations between HLA and autoimmune diseases, we here describe an analysis of DNA polymorphism in the human TNF-beta gene. The results show that the TNF-beta gene has only a low degree of DNA polymorphism, and that this is not associated with HLA antigens showing a strong association with autoimmune-like diseases.

Genetic Linkage↗

PubMed1993

5' insulin gene polymorphism confers risk to IDDM independently of HLA class II susceptibility.

The polymorphic variable number of tandem repeats in the 5' upstream region of the human insulin gene is a well-known non-human leukocyte antigen locus contributing to genetic susceptibility to IDDM. Controversy exists about the question as to whether INS susceptibility haplotypes are or are not preferentially inherited together with HLA-DR4 haplotypes. We investigated whether genetic interaction between INS and the HLA complex can be better defined using DQ genotypic and phenotypic markers in addition to DR serology. The 5' INS 1/1 genotype was positively associated with IDDM both in non-DR4 subjects (relative risk = 4.3; 95% confidence interval, 1.6-11.5) and DR4 subjects (relative risk = 4.2; 95% confidence interval, 1.9-9.0). Further subdivision of IDDM patients and matched control subjects according to HLA-DQA1 and HLA-DQB1 genotype or phenotype also failed to show any association between 5' INS and HLA class II genes in diabetic patients. The 5' INS and HLA class II polymorphisms therefore provide independent risk markers, which may both contribute to the genetic screening of a high-risk population among nondiabetic individuals.

Adolescent↗

PubMed1988

HLA-DQw3.1 and DQw3.2 associated exon polymorphisms detected by oligonucleotide probes.

HLA class II polymorphisms have been analyzed on the genomic level by two oligonucleotide probes corresponding to the DNA sequence coding for the amino acids 23-30 in the first domain of the beta chain of DQw3.1 and DQw3.2. Specific hybridization to single endonuclease fragments of DNA from some HLA homozygous cells was detected. Here we report the distribution of these DNA exon sequences among different DQ alleles, and demonstrate that the probes may be used to type for DQw3.1 and DQw3.2 respectively.

DNA↗

PubMed2001

The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behçet's disease.

Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.

5' Flanking Region↗

PubMed1990

HLA-D region genomic polymorphism associated with Takayasu's arteritis.

Takayasu's arteritis, with a strong predilection for women and particular geographic areas, has revealed significant association with human lymphocyte antigens (HLA) specificities. In the present study, the authors investigated for the first time the association of Takayasu's arteritis and HLA at the genomic level. By use of a restriction endonuclease Taq-I and a DQA cDNA probe, HLA-D region restriction fragment length polymorphism was examined in 32 Japanese patients. It was revealed that 65.6% of the patients shared a 6.6 kb fragment, although this fragment was found in 35.3% of the healthy Japanese (Chi square: 6.07, p less than 0.02). This finding suggest that HLA-D region gene variations determine susceptibility to Takayasu's arteritis.

Adult↗

PubMed1995

HLA class II genotyping: two assay systems compared.

In the last few years, a variety of DNA-based human leukocyte antigen (HLA) typing methods have emerged, revealing the extreme polymorphism of HLA genes. This polymorphism makes it difficult for a clinical laboratory to establish the best HLA typing strategy. In this study we have compared two techniques for performing HLA-DRB typing: a commercial rapid assay based on the polymerase chain reaction (PCR) followed by reverse dot-blot hybridization of the PCR products (the Inno-LiPA assay), and a method based on PCR followed by restriction fragment length polymorphism analysis. We found that both methods provide reliable results with a high rate of concordance (97%) and that Inno-LiPA is convenient for large-scale routine typing. However, if a high-resolution allelic typing is required, each method lacks accuracy but using them in association improves the accuracy of the results.

Alleles↗

PubMedDate not supplied

Polymorphism of human Ia antigens: gene conversion between two DR beta loci results in a new HLA-D/DR specificity.

The polymorphic HLA-DR beta-chains are encoded within the human major histocompatibility complex (MHC) by multiple loci resulting from gene duplications. Certain DR haplotypes can be grouped into families based on shared structural factors. We have studied the molecular basis of HLA-DR polymorphism within such a group which includes the haplotypes DR3, DR5 and DRw6. Molecular mapping of the DR beta-chain region allows true allelic comparisons of the two expressed DR beta-chain loci, DR beta I and DR beta III. At the more polymorphic locus, DR beta I, the allelic differences are clustered and may result from gene conversion events over very short distances. The gene encoding the HLA-DR3/Dw3 specificity has been generated by a gene conversion involving the DR beta I and the DR beta III loci of the HLA-DRw6/Dw18 haplotype, as recipient and donor gene, respectively. Based on which allele is found at DR beta III, the less polymorphic locus, two groups of haplotypes can be defined: DRw52a and DRw52b. The generation of HLA-DR polymorphism within the DRw52 supertypic group can thus be accounted for by a succession of gene duplication, divergence and gene conversion.

Alleles↗

PubMed2001

Identification of novel HLA-B27 ligands derived from polymorphic regions of its own or other class I molecules based on direct generation by 20 S proteasome.

HLA-B27 is strongly associated with ankylosing spondylitis. Natural HLA-B27 ligands derived from polymorphic regions of its own or other class I HLA molecules might be involved in autoimmunity or provide diversity among HLA-B27-bound peptide repertoires from individuals. In particular, an 11-mer spanning HLA-B27 residues 169-179 is a natural HLA-B27 ligand with homology to proteins from Gram-negative bacteria. Proteasomal digestion of synthetic substrates demonstrated direct generation of the B27-(169-179) ligand. Cleavage after residue 181 generated a B27-(169-181) 13-mer that was subsequently found as a natural ligand of B*2705 and B*2704. Its binding to HLA-B27 subtypes in vivo correlated better than B27-(169-179) with association to spondyloarthropathy. Proteasomal cleavage generated also a peptide spanning B*2705 residues 150-158. This region is polymorphic among HLA-B27 subtypes and class I HLA antigens. The peptide was a natural B*2704 ligand. Since this subtype differs from B*2705 at residue 152, it was concluded that the ligand arose from HLA-B*3503, synthesized in the cells used as a source for B*2704-bound peptides. Thus, polymorphic HLA-B27 ligands derived from HLA-B27 or other class I molecules are directly produced by the 20 S proteasome in vitro, and this can be used for identification of such ligands in the constitutive HLA-B27-bound peptide pool.

Amino Acid Sequence↗

PubMed1989

Polymorphism of three HLA-DR7 bearing major histocompatibility complex extended haplotypes.

We have studied the complexity of HLA class II region in DR7 bearing extended haplotypes by restriction fragment length polymorphism (RFLP). Genomic DNA from homozygous cell lines and from unrelated individuals was digested with a number of restriction endonucleases and probed with DR alpha, DR beta, DQ alpha and DQ beta cDNA probes. We detected RFLPs that distinguished subspecificities of DRA, DRB1, DQA1 and DQB1 chain genes. On the basis of polymorphism in these genes, three distinct types of DR7 bearing extended haplotypes could be identified: (1) B44 or Bw47 or B14, DR7a (DRA1, B1.1), DRw53a (DRA1,B4), DQw2 (DQA1.1, B1.1); (2) B13 or B40, DR7b (DRA1, B1.2), DRw53a (DRA1, B4), DQw2 (DQA1.1, B1.1); and (3) Bw57, DR7c (DRA2, B1.2), DRw53b (DRA2, B4), DQw9 (DQA1.2, B1.2). Available evidence indicates that independent examples belonging to a haplotype were similar in RFLP patterns, suggesting that most examples of an extended haplotype belonging to a subtype are similar. The results in the present study have important implications for immune function and disease susceptibility.

Blotting, Southern↗

PubMed1990

[Use of DNA polymorphism in forensic paternity evaluation].

Problematical paternity cases were additionally subjected to DNA-polymorphism analysis. 5 cases are reported, focusing on problems due to, 'silent' allele transmittance, relatively low probability for paternity, obvious occurrence of the extremely rare Rh gene complex CWc, involvement of brothers as putative fathers, non-paternity of a man although his W-value was 99.975%. The aim of this paper is to demonstrate the need for DNA-polymorphism analysis, if conventional blood group tests do not lead to a clear-cut decision. Extended typing of conventional blood group polymorphisms (except HLA) cannot compete with highly polymorphic DNA loci.

Adult↗

PubMed1986

Correlation between an HLA-DQ alpha length polymorphism of messenger RNA and serologically defined specificities (DQw1, DRw53, DR3+5).

mRNAs for the two chains of the HLA-DQ molecule were analyzed, in particular the DQ alpha mRNA whose polymorphism had previously been suggested (Schenning et al. 1984). Northern blot transfers of the mRNA of 12 LCLs and of B lymphocytes from a healthy donor were carried out. We report that a length polymorphism of DQ alpha mRNA exists, and we show that it can be correlated with serologically defined specificities (DQw1, DRw53, DR3+5). This correlation could be explained by a linkage disequilibrium, as these specificities are considered to be different from those carried by the DQ molecule (except for the DQw1 specificity).

DNA Restriction Enzymes↗

PubMed1992

[Gene amplification with PCR and sequence-specific HLA oligotyping].

Genetic polymorphism in the HLA-class II region has been identified by the analysis of the polymerase-chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant-typing kit [2] enables HLA-typing independent of gene expression and lymphocytes quality. One of the advantages of this technique is that the definition of subtypes is much better than is typing by serology.

Amino Acid Sequence↗

PubMed1988

HLA class II genes polymorphism in DR4 giant cell arteritis patients.

We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls.

DNA↗