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S Bahram

Publications and source records attributed to S Bahram.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sequencing based typing for genetic polymorphisms in exons, 2, 3 and 4 of the MICA gene.

We have established a sequencing based typing (SBT) method for detection of genetic polymorphism in the exon 2 to 4 domains of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) and applied it to allele typing of 130 healthy Japanese individuals. A 2.2-kb segment including exons 2, 3 and 4 of the MICA gene was amplified by a pair of generic primers followed by cycle sequencing using exon-specific nested primers. In total, 8 alleles were observed in a Japanese population and the most frequent allele was MICA008 with the gene frequency of 30.8%. MICA009 was the second most frequent (16.5%), while the rarest one was MICA007 (1.2%). MICA alleles displayed strong linkage equilibria with HLA-B antigens (i.e. MICA008 with B7, B48, B60 and B61; MICA009 with B51 and B52; MICA002 with B35, B39, B58 and B67; MICA004 with B44, MICA007 with B13 and B27; MICA010 with B46, B62 and B48, MICA012 with B54, B55, B56 and B59; MICA019 and B70, B71 and B62). Recently, the B48 haplotype has been reported to lack the entire MICA gene by a large-scale deletion in a Japanese population. Among 8 serologically B48 homozygous individuals, 4 were found to represent this MICA null allele as assessed by no polymerase chain reaction (PCR) amplification using MICA-specific primers, while the remaining four possessed the intact MICA gene with MICA008 or MICA010.

Asian People↗
PubMed1999

Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene.

The HLA-Cw6 antigen has been associated with psoriasis vulgaris despite racial and ethnic differences. However, it remains unclear whether it is the HLA-Cw6 antigen itself or a closely linked, hitherto unidentified, locus that predisposes to the disease. Here, in order to map the susceptibility locus for psoriasis vulgaris precisely within the HLA class I region, 11 polymorphic microsatellite markers distributed throughout a 1060 kb segment surrounding the HLA-C locus were subjected to association analysis in Japanese psoriasis vulgaris patients. Statistical analyses of the distribution and deviation from Hardy-Weinberg equilibrium of the allelic frequency at each micro-satellite locus revealed that the pathogenic gene for psoriasis vulgaris is located within a reduced interval of 111 kb spanning 89-200 kb telomeric of the HLA-C gene. In addition to three known genes, POU5F1, TCF19 and S, this 111 kb fragment contains four new, expressed genes identified in the course of our genomic sequencing of the entire HLA class I region. Therefore, these seven genes are the potential candidates for susceptibility to psoriasis vulgaris.

Adult↗
PubMed1998

Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene.

A growing number of non-MHC-encoded class I-related molecules have been shown to perform diverse, yet essential, functions. These include T cell presentation of bacterially derived glycolipidic Ags by CD1, transcytosis of maternal IgG by the neonatal Fc receptor, enriched presence and plausible function within exocrine fluids of the Zn-alpha2-glycoprotein, subversion of NK cytolytic activity by the CMV UL18 gene product, and, finally, crucial involvement in iron homeostasis of the HFE gene. A recently described member of this family is the MHC class-I related (MR1) gene. The most notable feature of MR1 is undoubtedly its relatively high degree of sequence similarity to the MHC-encoded classical class I genes. The human chromosome 1q25.3 MR1 locus gives rise not only to the originally reported 1,263-bp cDNA clone encoding a putative 341-amino acid polypeptide chain, but to many additional transcripts in various tissues as well. Here we define the molecular identity of all human and murine MR1 isoforms generated through a complex scenario of alternative splicing, some encoding secretory variants lacking the Ig-like alpha3 domain. Moreover, we show ubiquitous transcription of these MR1 variants in several major cell lineages. We additionally report the complete 18,769-bp genomic structure of the MR1 locus, localize the murine orthologue to a syntenic segment of chromosome 1, and provide evidence for conservation of a single-copy MR1 gene throughout mammalian evolution. The 90% sequence identity between the human and mouse MR1 putative ligand binding domains together with the ubiquitous expression of this gene favor broad immunobiologic relevance.

Amino Acid Sequence↗
PubMed1997

Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet disease.

A member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), MICA, has been recently identified near the HLA-B gene on the short arm of human chromosome 6. The predicted amino acid sequence of the MICA chain suggests that it folds similarly to typical class I chains and may have the capacity to bind peptides or other short ligands. Therefore, MICA is predicted to have a specialized function in antigen presentation or T cell recognition. During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmembrane (TM) region of the MICA gene. In 68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite sequence were detected. One of them contained an additional one base insertion that created a frameshift mutation resulting in a premature termination codon in the TM region. This particular allele may encode a soluble, secreted form of the MICA molecule. In addition, we have investigated this microsatellite polymorphism in 77 Japanese patients with Behcet disease, which is known to be associated with HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc = 0.00055) than in a control population. Furthermore, the (GCT/AGC)6 allele was present in all B51 positive patients and in an additional 13 B51 negative patients. These results suggest the possibility of a primary association of Behcet disease with MICA rather than HLA-B.

Asian People↗
PubMed1997

Allelic variants of the human MHC class I chain-related B gene (MICB).

The human major histocompatibility complex (MHC) is located within a 4 megabase segment on chromosome 6p21.3. Recently, a highly divergent MHC class I chain-related gene family, MIC was identified within the class I region. The MICA and MICB genes in this family have unique patterns of tissue expression. The MICA gene is highly polymorphic, with more than 20 alleles identified to date. To elucidate the extent of MICB allelic variations, we sequenced exons 2 (alpha 1), 3 (alpha 2), 4 (alpha 3), and 5 (transmembrane) as well as introns 2 and 4 of this gene in 46 HLA homozygous B-cell lines. We report the identification of eleven alleles based on seven non-synonymous, two synonymous, and four intronic nucleotide variations. Interestingly, one allele has a nonsense mutation resulting in a premature termination codon in the alpha 2 domain. Thus, MICB appears to have fewer alleles than MICA, not unlike the allelic ratio between the HLA-C and -B loci. A preliminary linkage analysis of the MICB alleles with those of the closely located MICA and HLA-B genes revealed no conspicuous linkage disequilibrium between them, implying the presence of a potential recombination hotspot between the MICB and MICA genes.

Alleles↗
PubMed1997

Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian.

We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain-related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4, 5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been detected in various HLA-homozygous B cell lines. Here we present allele frequencies for this trimeric short tandem repeat (STR) in 604 unrelated individuals collected from nine human populations (Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using the polymerase chain reaction (PCR) combined with fluorescent-based automated fragment detection technology. All alleles were present in each population, but allelic distributions varied from one population to another. No new alleles (such as A7 or A8) were identified. The evolutionary and structural significance of these data as well as the potential application to forensic medicine is discussed.

Alleles↗
PubMed1997

MICA gene and ankylosing spondylitis: linkage analysis via a transmembrane-encoded triplet repeat polymorphism.

In order to address the possibility that the MICA gene located 47 kb upstream from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we have investigated microsatellite polymorphism in the transmembrane region of MICA in Caucasian patients with AS. The microsatellite allele consisting of 4 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc<0.0000001) than in the ethnically matched control group. However, the frequency of the (GCT/AGC)4 allele was significantly low in the B27-positive patients than in the B27-positive healthy controls (Pc=0.0145). These observations suggest that B27 itself remains the primary genetic marker for AS, although the significantly dissimilar phenotype frequency of the (GCT/AGC)4 allele in B27-positive patients and healthy individuals may reflect the existence of other genetic factor(s) in the HLA-B27 haplotype involved in the development of AS.

Alleles↗
PubMed1996

Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium.

Conventional major histocompatibility complex (MHC) class I genes encode molecules that present intracellular peptide antigens to T cells. They are ubiquitously expressed and regulated by interferon gamma. Two highly divergent human MHC class I genes, MICA and MICB, are regulated by promoter heat shock elements similar to those of HSP70 genes. MICA encodes a cell surface glycoprotein, which is not associated with beta 2-microglobulin, is conformationally stable independent of conventional class I peptide ligands, and almost exclusively expressed in gastrointestinal epithelium. Thus, this MHC class I molecule may function as an indicator of cell stress and may be recognized by a subset of gut mucosal T cells in an unusual interaction.

Animals↗
PubMed1996

Allelic repertoire of the human MHC class I MICA gene.

The hallmark of the classical major histocompatibility complex (MHC) class I molecules is their astonishing level of polymorphism, a characteristic not shared by the nonclassical MHC class I genes. A distinct family of MHC class I genes has been recently identified within the human MHC class I region. The MICA (MHC class I chain-related A) gene in this family is a highly divergent member of the MHC class I family and has a unique pattern of tissue expression. We have sequenced exons encoding the extracellular alpha1, alpha2, and alpha3 domains of the MICA gene from twenty HLA homozygous typing cell lines and four unrelated individuals. We report the identification of eleven new alleles defined by a total of twenty-two amino acid substitutions. Thus, the total number of MICA alleles is sixteen. Interestingly, a tentative superimposition of MICA variable residues on the HLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding cleft, apparently bordering an invariant ligand binding site.

Alleles↗
PubMed1994

A second lineage of mammalian major histocompatibility complex class I genes.

Major histocompatibility complex (MHC) class I genes typically encode polymorphic peptide-binding chains which are ubiquitously expressed and mediate the recognition of intracellular antigens by cytotoxic T cells. They constitute diverse gene families in different species and include the numerous so-called nonclassical genes in the mouse H-2 complex, of which some have been adapted to variously modified functions. We have identified a distinct family of five related sequences in the human MHC which are distantly homologous to class I chains. These MIC genes (MHC class I chain-related genes) evolved in parallel with the human class I genes and with those of most if not all mammalian orders. The MICA gene in this family is located near HLA-B and is by far the most divergent mammalian MHC class I gene known. It is further distinguished by its unusual exon-intron organization and preferential expression in fibroblasts and epithelial cells. However, the presence of diagnostic residues in the MICA amino acid sequence translated from cDNA suggests that the putative MICA chain folds similarly to typical class I chains and may have the capacity to bind peptide or other short ligands. These results define a second lineage of evolutionarily conserved MHC class I genes. This implies that MICA and possibly other members in this family have been selected for specialized functions that are either ancient or derived from those of typical MHC class I genes, in analogy to some of the nonclassical mouse H-2 genes.

Amino Acid Sequence↗
PubMed1992

Allelic variants of the human putative peptide transporter involved in antigen processing.

Antigen processing for presentation of peptide epitopes by major histocompatibility complex (MHC) class I molecules involves genes in the MHC class II region. Among these, PSF1 and PSF2 encode subunits of a transporter, which presumably delivers cytosolic peptides across the endoplasmic reticulum membrane to class I molecules. This close functional relationship of the transporter and class I heavy chain genes and their linkage within the MHC raise the question of whether PSF1 and PSF2, like most class I genes, are polymorphic. By single-strand conformation polymorphism analysis and DNA sequencing, a small number of amino acid sequence variants of both PSF1 and PSF2 was identified in a panel of cell lines. This limited polymorphism may contribute to a higher degree of variability at the level of the functional transporter, in which different alleles of the PSF1 and PSF2 subunits may be combined. A possible involvement of the PSF1 and PSF2 genes in susceptibility to MHC-associated diseases was examined in a preliminary assessment in patients with ankylosing spondylitis, insulin-dependent diabetes mellitus, or celiac disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Two putative subunits of a peptide pump encoded in the human major histocompatibility complex class II region.

The class II region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class I molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class I molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class II DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by gamma interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class I molecules, although a distinct function of PSF2 cannot be ruled out.

ATP Binding Cassette Transporter, Subfamily B, Mem↗