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At least 955 records · Page 53Linked to original sources
PubMed2000

Characteristics of HLA class I and class II polymorphisms in Rwandan women.

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

Alleles↗
PubMedDate not supplied

Relationship between DQ alpha and DQ beta RFLP and cell surface polymorphisms of class II HLA antigens.

DQ alpha and beta DNA probes of the human major histocompatibility complex (MHC) were hybridized to restriction enzyme-digested genomic DNA with the aim of establishing a correspondence between the polymorphisms recognized by classical serology and DNA restriction fragment length polymorphisms (RFLP). In DR homozygous human cell lines, three distinct PstI fragments were recognized by the DQ alpha probe and four PstI fragments were recognized by the DQ beta probe. Each fragment was associated with a different group of DR antigens. Three allelic forms of either DX alpha or beta genes were identified, but none showed any strong association with DR or DQ. Family segregation analysis at the DNA level further confirmed the DR linkage of the DQ alleles in estimations of gene frequencies of different alleles of DQ alpha, DQ beta, DX alpha and DX beta. Evidence was presented that the DQ alpha and DQ beta allelic forms described at the DNA level correspond to polymorphic determinants at the cell surface which can be defined serologically or in cellular assays. Our data suggest that the HLA-DQ subregion-encoded alloantigens should be defined at the individual alpha and beta chain levels.

Alleles↗
PubMed2001

Polymorphism of human HLA-DRB1 antigens generated by genetic exchange between DR2 (DRB1*15011) and DR6 (DRB1*1405) alleles: a novel DRB1 allele (DRB1*1437) identified in a Paiwan tribe member of Taiwan.

We report herein the identification of a new DRB1 allele using sequence-based typing (SBT). This novel allele, HLA-DRB1*1437, was found in an aboriginal individual from the Paiwan tribe in the southern part of Taiwan. This individual was typed by SBT method as having an HLA genotype of HLA-A*02011/0203, HLA-B*15011/3901, HLA-DRB1*11011/1437, HLA-DRB3*0202/0202, and HLA-DPB1*0501/1301. This new allele differs from DRB1*1309 in the 5'-end nucleotide sequence of polymorphic exon 2 at codon 16 (CAT-->CAA; H16Q), codon 37 (AAC-->TTC; R37F), codon 47 (TTC-->TAC; F47Y), and codon 58 (GCC-->GCT; both specify alanine). By sequence comparison, it was found that this new allele has a 5'-end sequence (from amino acid residues 7 to 66) identical to that found in the DRB1*1405 allele and a 3'-end sequence (from amino acid residues 58 to 94) identical to that found in the DRB1*15011 allele. Both DRB1*1405 and DRB1*15011 alleles have been identified among the Paiwan members (Note).

Alleles↗
PubMed2002

In vivo pharmacodynamic effects of Hu1D10 (remitogen), a humanized antibody reactive against a polymorphic determinant of HLA-DR expressed on B cells.

The humanized monoclonal antibody Hu1D10 (Remitogen, Protein Design Labs, Fremont, CA) recognizes a polymorphic determinant of human leukocyte antigen-DR expressed on the majority of B-cell lymphomas and on normal B cells of most individuals. Hu1D10 mediates complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis of 1D10 antigen (Ag)-positive B cells in vitro. The 1D10 Ag is expressed on a variety of tissues but is restricted primarily to lymphocytes, macrophages, and mesenchymal dendritic cells. The safety and pharmacology of Hu1D10 were investigated in rhesus macaques. Animals were prescreened for 1D10 Ag expression on circulating B cells. Sixteen animals received either placebo (4 Ag+ animals), 1 mg/kg Hu1D10 (4 Ag+ animals), or 10 mg/kg Hu1D10 (4 Ag+ animals and 4 Ag- animals) daily via intravenous (i.v.) bolus-injection for 5 consecutive days, and 4 Ag+ animals received 10 mg/kg Hu1D10 via 90 min i.v. infusion x 5 days. Bolus-injection of Hu1D10 resulted in type 1 hypersensitivity reactions in the majority of Ag+ animals and one death due to anaphylaxis. Slow infusion of Hu1D10 was associated with only mild hypersensitivity reactions after the first dose but not subsequent doses. In animals treated with 10 mg/kg Hu1D10 via bolus-injection, the median terminal elimination half-life of Hu1D10 was 2.6 and 8.4 days in Ag+ and Ag- animals, respectively. Administration of Hu1D10 to Ag+ animals resulted in rapid and profound depletion of circulating B cells for 7-10 days following the last dose. No B-cell depletion was observed in Ag- animals, despite slower elimination of Hu1D10. These studies demonstrate that Hu1D10 reacts with antigen-presenting cells in rhesus macaques. It can be safely administered as a slow i.v. infusion but causes severe toxicity when given as a bolus. This study provides the foundation for testing Hu1D10 for the treatment of B-cell malignancies in humans.

Anaphylaxis↗
PubMed1998

Polymorphism within the HLA-DQB1*02 promoter associated with susceptibility to coeliac disease.

Susceptibility to coeliac disease is associated with a particular HLA-DQ alpha beta heterodimer encoded by the DQA1*0501 and DQB1*02 genes. A single base polymorphism in the DQB1*02 promoter region in DR7, DQA1*0201, DQB1*02 haplotypes was observed, associated with an increased susceptibility to the disease. This finding suggests a novel mechanism of susceptibility to immune-mediated diseases.

Alleles↗
PubMed1992

Exonic polymorphism vs intronic simple repeat hypervariability in MHC-DRB genes.

Gene products encoded by the major histocompatibility complex often exhibit a high degree of polymorphism. In humans the HLA-DR polymorphism is due to more than 50 alleles with varying exon 2 sequences. Each group of DRB alleles contains a certain form of the basic simple repeat motif (gt)n(ga)m in intron 2. Identical alleles can be differentiated on the basis of the hypervariable repeat. In this study focused on cattle (Bos taurus) we identified different Bota-DRB alleles in a limited survey by amplification via polymerase chain reaction and sequencing. In addition DRB exon 2 sequences were also obtained from eight additional hoofed animal species (seven horned artiodactyls and one pig) revealing artiodactyl-specific polymorphic and nonpolymorphic substitutions. In the genus Bos the intronic simple repeat variability was compared with exonic DRB polymorphism. As in humans all Bota-DRB exons were always associated with specifically organized basic simple repeat structures. Yet the extent of simple repeat variability was lower in cattle compared to humans. Selective breeding in the process of domestication might be responsible for the diminished intronic hypervariability. Nevertheless, the hypermutable simple repeat sequences have been preserved in the same position and with the same principal structure for at least 70 x 10(6) years of evolution. Unexpectedly, the rate of intronic simple repeat and exonic changes appear quite similar.

Alleles↗
PubMed2000

A robust test for assortative mating.

Testing for random mating in human populations is difficult due to confounding factors such as ethnic preference and population stratification. With HLA, the high level of polymorphism is an additional problem since it is rare for couples to share the same haplotype. Focus on an ethnically homogeneous population, where levels of polymorphism at HLA loci are more limited, may provide the best situation in which to detect non-random mating. However, such populations are often genetic isolates where there may be inbreeding to an extent that is difficult to quantify and account for. We have developed a test for random mating at a multiallelic locus that is robust to stratification and inbreeding. This test relies on the availability of genotypic information from the parents of both spouses. The focus of the test is on families where there is allele sharing between the parents of both spouses, so that potential spouses could share an allele. Denoting the shared allele at the locus of interest by A, then under the assumption of random mating, heterozygous parents AX should transmit allele A equally as frequently as allele X to their offspring. When there is positive (negative) assortative mating, A will be transmitted more (less) often than X. The power of the test has been computed in a number of situations. Data on high resolution HLA haplotypes from the Hutterite population were reinvestigated by the proposed test. The test detects significant negative assortative mating when the parental origin of the shared haplotype is taken into account.

Alleles↗
PubMedDate not supplied

Prenatal identification of paternity. HLA typing helpful after rape.

The HLA antigens system is extremely polymorphic, and HLA typing is now widely used for both the exclusion and the positive assignment of paternity. We have also used HLA typing for identification of paternity of fetal cells in a pregnancy detected a few weeks after the rape of a woman. The HLA typing indicated that the father of the fetus was the woman's husband, with a probability of 25:1 (96%), before the time the rapist could also be tested. Subsequently, the accused rapist was excluded as a potential father because he lacked all of the paternal antigens detected in the fetus. This prediction was confirmed after delivery.

Adult↗
PubMed2001

Heat-shock protein 70-1 and HLA class II gene polymorphisms associated with celiac disease susceptibility in Navarra (Spain).

Heat shock proteins (HSP) are thought to play a role in the immune response making probable their contribution to celiac disease (CD). We studied the polymorphisms in the 5' regulatory region of the HSP70-1 gene and performed genomic HLA-DQ and -DR typing in 128 CD patients and 94 healthy controls from Navarra (Spain). The frequency of the C allele of the HSP70-1, characterized by the intermediate electrophoretic mobility of DNA, was significantly increased among CD patients (64.5% vs 37.2%. p <1 x 10(-7)). When subjects were stratified by the HLA II genotype, differences were statistically significant between DR3-negative or DR3-DQB1*02-negative CD patients and matched controls. Homozygosity for the DQB1*02 allele was present in 48.4% of CD patients and 12.8% of controls (OR = 6.4; CI:3.1 to 13.8; p <1 x 10(-7)). Similar increased risk was observed for DQB1*02/*02, DRB1*03/-, or DRB1*03/07 patients. Furthermore, those individuals expressing the classical HLA alleles in CD (DQB1*02/*02, DRB1*03/*07) who also carried the HSP70-1 CC genotype were twelve times more likely to develop the disease than the matched controls. We therefore conclude that although HSP70-1 gene does not seem to be primarily associated with CD, it might be a component of the high risk haplotype, playing a role as an additional predisposing gene for the disease.

5' Untranslated Regions↗
PubMed2002

HLA-Cw6 specificity and polymorphic residues are associated with susceptibility among Chinese psoriatics in Taiwan.

Previous serotyping in Chinese patients has failed to confirm an association between HLA-Cw6 and psoriasis. As serotyping has proved to be less valuable in the determination of HLA-C, genotyping of HLA-C in 68 Taiwanese psoriasis vulgaris (PSV) patients was performed using polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR-SSOPH) of HLA-Cw genes. Compared to 213 non-PSV control subjects, HLA-Cw6 was significantly associated with PSV (16.18% of PSV patients vs 5.16% of controls; odds ratio 3.53, Pc</=10(-4)). The amino acid residues on the heavy chain of the HLA-Cw antigens from exon one to exon five were also analyzed. Asp 9, Ser 24, Ala 73, Asp 90, Trp 97, Trp 156 and Asn 77/Lys 80 were found to be positively associated with PSV ( Pc</=0.0044, 0.0008, 0.0026, 0.0014, 0.039, 0.0020 and 0.0000, respectively).

Adolescent↗
PubMed2000

HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis.

Cardiac sarcoidosis occurs in 1-5% of sarcoidosis patients. We previously reported a significant increase of the uncommon TNFA (tumor necrosis factor alpha) allele, TNFA2 with cardiac sarcoidosis in Japanese. In order to precisely localize the susceptible locus for cardiac sarcoidosis within the HLA region, genetic polymorphisms of classical HLA genes, non-classical HLA class II genes such as HLA-DMA and -DMB genes and several genes involved in the class I-mediated antigen presentation pathway (TAP1, TAP2, LMP2 and LMP7) were investigated. Further, association analyses using four polymorphic microsatellite markers located around the TAP1 and TNFA genes were also carried out. As a result, HLA-DQB1*0601 was found to be the most significantly associated allele, being more significantly increased than TNFA2. No significant increase of the DR52-associated DRB1 alleles (DRB1*03, 05, 06 and 08), which was suggested to be primarily associated with lung sarcoidosis, was observed in cardiac sarcoidosis. A primary role of DQB1*0601 in determination of the susceptibility to cardiac sarcoidosis was supported by association analysis using four polymorphic microsatellite markers, in which only the TAP1 microsatellite locus, the nearest marker to the DQB1 gene among the microsatellites tested, displayed a significant positive association with cardiac sarcoidosis. On the other hand, the HLA-DQB1*0501-DQA1*0101-DRB1*0101-B7 haplotype showed a negative association with the disease, as similarly observed in lung sarcoidosis. Thus, molecular mechanism for controlling the development of the disease related to HLA molecules are different between cardiac and lung sarcoidosis, whereas those for conferring a resistant trait may be similar to each other.

Alleles↗
PubMed1997

Polymorphism of the HLA-DRB1 locus in Colombian, Ecuadorian, and Chilean Amerinds.

We have characterized the DRB1 genotypes in a sample of 64 South American Indians drawn from populations in Chile, Colombia, and Ecuador. No novel DRB1 alleles were found in the total of 17 different alleles characterized, indicating that rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B. Comparison between Chilean and Colombian/Ecuadorian samples revealed no major differences in their allelic frequencies. In the combined Amerind sample the HLA-DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and 22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies reported here to agree with findings in other Amerind groups. The high frequencies of both HLA-DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with their absence in Siberian samples, suggest that migratory groups other than Siberians may have been involved in the peopling of the Americas.

Alleles↗