Polymorphism of HLA-DRw52-associated DRB1 genes as defined by sequence-specific oligonucleotide probe hybridization and sequencing (original) (raw)
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Single nucleotide polymorphisms in the regulatory regions of the HLA-DRB-expressed genes
Human Immunology, 2005
DRB genes encode proteins that play an important role in the immune response, and their expressional regulation is crucial to the immune reaction. Sequence variation at the regulatory region can directly affect the gene expression level. The aim of the present study was to use Chinese samples to investigate the variation in the regulation region of the human leukocyte antigen (HLA)-DRB-expressed genes. Seventyone single nucleotide polymorphisms (SNPs) were found in the four HLA-DRB-expressed genes. By comparing these data with SNPs in the U.S. National Center for Biotechnology Information dbSNP database, 69 SNPs (97.2%) were found to be novel. In addition, two genetic variations of insertion-deletion polymorphisms were discovered within the regulatory region of HLA-DRB1 gene. These polymorphisms can be used as resources of markers for association studies of complex diseases, for assessment of individual predisposition to diseases, and as research markers for population genetics and evolution.
Six newly identified HLA-DRB alleles: DRB1*1121, *1419, *1420, *1421, DRB3*0203 and DRB5*0103
Tissue Antigens, 1996
Seven samples with irregular PCR-SSO hybridization patterns, observed during routine HLA-DRB typing, were studied in more detail. Group-specific amplification, followed by hybridization with relevant SSOs strengthened the suggestion that these samples contained new DRB alleles. DRB exon 2 seg-~ ments were amplified, cloned and sequenced and revealed: DRB 1 * 1 12 1 [MUL] is similar to DRB I * 1102 in which codon 85 changed from G?T(V) ~ into GTC(A); DRB1*1419 [AKKAL] is similar to DRB1*1402 with codon , 71 changed from AGG(R) into AAG(K); DRB 1*1420 [OND-5297 11 is a DRB 1 * 1406 with codon 37 changed from AAC(N) into TTC(F); DRB 1 * 1421 [TGI] is similar to DRB1*1417 with codon 71 changed from AGG(R) into AAG(K); DRB3*0203 [POS] is similar to DRB3*0202 in which codons 37-38 are changed from TAC GCG(YA) into TCC GTC(SV); DRB5*0103 was found in two unrelated individuals of Oriental origin [IND-24 and IND-591 and is similar to DRB5*0102 in which codon 71 AGG(R) changed into ACG(T). This particular sequence variation at position 7 1 has not yet been described. The new DRB sequences were confirmed using the sequencing based typing technique. Low resolution PCR-SSP typing failed to amplify two of the DRB 1 * 14 variants, whereas high resolution PCR-SSP resulted in aberrant patterns. Class I1 alloantisera identify the codon 7 1 changes in DRBl"1419 and "1421 with respect to the MCI('DRI+DR4') epitope.
DNA sequence analysis of the HLA-DRw12 allele
Human Immunology, 1989
The complete DNA sequence of a DRy3 chain cDNA encoding the DRwI2 allele has been determined. The sequence of this DRBI allele reveals a structural relationship to the group of other DRB1 genes found on DRw 5 2 haplotypes, such as DR3, -w l 1, -w13, -w14, and-wS. The structural similarities among this group of alleles are particularly evident in the first hypervariable as well as in the 3' untranslated region. The second tzypervariable region contains a unique sequence not identified in any other DRB I allele. The third hyperrariable region appears to have arisen by gene conversion events involving two DRB1 chain genes, DR7 and DRI or DR2/Dw21. ABBREVIATIONS HV hypervariable IHW International Histocompatibility Workshop
Human Immunology, 2013
Association between HLA-DRB1 and a large number of diseases such as multiple sclerosis, type I diabetes and rheumatoid arthritis has been demonstrated. In the present study, we attempted to identify and characterize potential microsatellites in the HLA-DRB1 gene region to find specific markers for genotyping and linkage analysis of this gene. The microsatellites including M2_3_22, M2_2_36, D6S2878, D6S2805, D6S2879 and D6S2880 were selected from microsatellite resource in the Major Histocompatibility Complex database (dbMHC). In silico analysis showed that only M2_3_22 was specific for HLA-DRB1. Moreover, our findings revealed some more accurate characteristics of the other investigated microsatellites. M2_3_22 existed as a single copy in all the MHC haplotype sequences and was located next to HLA-DRB1. Therefore, a new set of primers compatible with all the last published MHC haplotype sequences were designed and used to amplify M2_3_22 in 164 DNA samples obtained from unrelated Iranian individuals. M2_3_22 was successfully amplified in all DNA samples and three different alleles were identified. This locus was found in the Hardy-Weinberg equilibrium (P > 0.05) in the studied population. Together, the findings suggested that M2_3_22 could be introduced as a specific locus in the HLA-DRB1 gene region for linkage analysis and disease association studies.
Molecular Immunology, 1991
A novel TaqI restriction fragment length polymorphism (RFLP) of 4.15 kb is reported using a DR beta probe (pRTV1). This fragment corresponds to the DRBI locus and allows the subdivision at the DNA level of the DRB1*0301 allele (DR3 antigen), which had not previously been reported. Both splits also disting~sh each of the two DR3-bearing extended haplotypes (HLA-B~,SCOI,DR~,DQW~,DW~~ and B~~,F~C~O,DR~,DQW~,DW~S) found associated to several autoimmune diseases as insulindependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE) and myasthenia gravis. The fact that no polymorphism in the DRB1'0301 coding DNA sequence has been detected indicates that DRB1*0301 intronic, regulatory of neighbouring sequences might also contribute to differential disease associations (and pathogenic mechanisms) found linked to each of the two DR3-bearing haplotypes, i.e. IDDM and B8,DR3,Dw24 in North European/American Caucasoids vs IDDM and B18,DR3,Dw25 in Mediterraneans; SLE and B8,DR3,Dw24 in children vs SLE and B18,DR3,Dw25 in Spanish adults.
A new HLA-DRB1*04 allele: DRB 1*0420
Tissue Antigens, 1995
DNA from two related individuals. Briefly, DNA was amplified using primers DRBAMP4 and DRBAMPB (2), and purified by separation on