A newHLA-DRB1 * 13 allele (DRB1 * 1318) with a shortDRB1*08 sequence

The nucleotide sequence data reported in this paper have been submitted to the EMBL/GenBank nucleotide sequence database and have been assigned the accession number Z48631. The name listed for this sequence was officially assigned by the WHO Nomenclature Committee in November 1994. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (Bodmer et al. 1994), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report     

The HLA molecules DQA1*0501/B1*0201 and DQA1*0301/B1*0302 share an extensive overlap in peptide binding specificity

Assays to measure the binding capacity of peptides for HLA-DQA1*0501/B*0201 (DQ2.3) and DQA1*0301/B*0302 (DQ3.2) were developed using solubilized MHC molecules purified from EBV-transformed cell lines. These quantitative assays, based on the principle of the inhibition of binding of a high-affinity radiolabeled ligand, were validated by examining the binding capacity of known DQ-restricted epitopes or ligands. The availability of these assays allowed an investigation of patterns of cross-reactivity between different DQ molecules and with various common DR molecules. DQ2.3 and DQ3.2 were found to have significantly overlapping peptide binding repertoires. Specifically, of 13 peptides that bound either DQ2.3 or DQ3.2, nine (69.2%) bound both. The molecular basis of this high degree of cross-reactivity was further investigated with panels of single substitution analogs of the thyroid peroxidase 632-645Y epitope. It was found that DQ2.3 and DQ3.2 bind the same ligands by using similar anchor residues but different registers. These data suggest that in analogy to what was previously described for HLA-DR molecules, HLA-DQ supertypes characterized by largely overlapping binding repertoires can be defined. In light of the known linkage of both HLA-DQ2.3 and -DQ3.2 with insulin-dependent diabetes mellitus and celiac disease, these results might have important implications for understanding HLA class II autoimmune disease associations.     

A new DRB1 * 1202 allele (DRB1 * 12022) found in association with DQA1 * 0102 and DQB1 * 0602 in two Black narcoleptic subjects

The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number L34353. The name listed for this sequence has been officially assigned by the WHO Nomenclature Committee in August 1994. This follows the agreed policy that subject to the conditions stated in the most recent Nomenclature Report (Bodmer et al 1994), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report     

CYP1A1*2 and CYP1A1*3 polymorphisms cosegregate in the Indian population

Several ethnic groups have been genotyped for polymorphisms at the CYP1A1 gene locus that encodes the enzyme that catalyzes the initial step in the metabolism of polycyclic aromatic hydrocarbons. Two of the CYP1A1 polymorphisms, namely, CYP1A1*2 and CYP1A1*3 are reported to cosegregate among the Japanese and to a lesser extent in Caucasians, but not in people of African descent. In the absence of such information in the Indian population, the frequency of the CYP1A1*2 polymorphism was determined in this study, using DNA samples from 649 ethnic Indians who had been earlier genotyped for the CYP1A1*3 polymorphism. Analysis of the combined genotype data revealed that the two polymorphisms cosegregate in the Indian population.     

HLA—DRα＊0101、DRβ1＊04051和DRβ1＊07011的分子克隆、测序及空间结构模建

目的：Y国探索HLA（human leukocyte antigens,HLA)不同分子的空间结构差异与功能之间的关系以及结构差异能否对预测造血干细胞移植GVHD（graft-versus-host disease,GVHD)的发生奠定基础。方法：提取人外周血总RNA,RT-PCR扩增HLA——DR等位基因全序,连接、转化大肠杆菌后并测序,将第二外显子氨基酸序列输入微机,通过INTER-NET传送至SWISS-MODELLING蛋白质空间结构模建服务器进行结构模建,结果：本文反转录了2例健康无血缘关系个体的HLA-DR位点基因全序,测序结果与HLA-DRα*0101、DRβ1*04051和DRβ1*07011的公布序列完全一致。对后两者的蛋白质空间结构模建发现它们在空间结构上存在显著差异。结论：对HLA基因位点进行全长测序可以明确判断基因型别;空间结构模建可以直观地辨别HLA不同舂子在空间结构上的差异。这为研究HLA结构与功能的关系以及HLA不完全相合的造血干细胞移植后预测GVHD的研究提供实验基础。     

Human orosomucoid polymorphism: molecular basis of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S

The human orosomucoid (ORM) is controlled by two closely linked loci, ORM1 and ORM2, and two tandem genes, AGP1 and AGP2, encoding the proteins produced by the two loci, have been cloned. In this study the molecular basis of ORM1 polymorphism was investigated. For the detection of mutations the products of the six exons of each gene, amplified by the polymerase chain reaction (PCR), were screened by single-strand conformation polymorphism analysis. Subsequently, the exons with an altered migration pattern were gene-specifically amplified by nested PCR. Sequencing of the gene-specific PCR products showed that the three common ORM1 alleles result from A→G transitions at the codons for amino acid positions 20 in exon 1 and 156 in exon 5 of the AGP1 gene: ORM1*F1 was characterized by CAG (Gln) and GTG (Val), ORM1*F2, by CAG (Gln) and ATG (Met), and ORM1*S, by CGG (Arg) and GTG (Val). The phylogenesis of the genes encoding these three ORM1 alleles is discussed. Received: 5 September 1996     

AM1* parameters for gold

We report the parameterisation of AM1* for gold. The basis set for gold contains one set each of s-, p- and d-orbitals. AM1* parameters are now available for H, C, N, O and F (which use the original AM1 parameters), Al, Si, P, S, Cl, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Zr, Mo, I and Au. The performance and typical errors of AM1* for gold are discussed.     

DPB1 * BR: an Mhc class II DPB1 allele (DPB1 * 6601) of negroid origin

The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the accession number X96986. The nameDPB1 ^* 6601 was officially assigned by the WHO Nomenclature Committee in May 1996. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (Bodmer et al. 1995), names will be assigned to new sequences as they are identified. Lists of such sequences will be published in the following WHO Nomenclature Report     

抑癌基因DLC-1的研究进展

DLC-1(肝癌缺失基因1)是近年来被发现的一种重要的抑癌基因,目前研究发现其在多种肿瘤的发生、发展过程中产生了重要的作用。随着基因技术及分子生物技术的飞速发展,关于DLC-1基因以及与之相关的上、下游靶基因,DLC-1基因的甲基化修饰及其相互作用的信号传导通路的研究将更深入、更彻底、更清楚。通过构建肿瘤动物实验模型,我们可以对人类各种肿瘤进行去甲基化药物治疗,分析实验结果,综合评估治疗指征,为临床上对肿瘤的治疗提供理论基础及实践指导。相信在不久的将来,针对DLC-1基因在肿瘤分子生物学研究有望成为多种肿瘤诊断、治疗的突破。     

Comparison of acid phosphatase ACP1 variants by isoelectric focusing and conventional electrophoresis: identification of three new alleles, ACP1*N, ACP1*P and ACP1*S

Three new alleles of human red cell acid phosphatase (ACP1) have been identified by comparison with previously reported variants using three different electrophoretic techniques. Family data are available on all the variants and show genetic transmission of the rare alleles ACP1*N, ACP1*P and ACP1*S. Further evidence of a rare allele demonstrating reversed 'A' activity is also described. The report documents the need to use several electrophoretic techniques to characterize new or rare variants.     

A PGM1*1A variant with a reduced activity

An adverse homozygosity at the phosphoglucomutase-1 (PGM1) locus was detected in a family by electrophoresis on starch gels. Isoelectric focusing on polyacrylamide gels could clearly demonstrate a faint band at the same position as that of PGM1 1A in the mother and the child. Further analysis of other family samples and densitometric evaluation of the stained bands revealed the genetic transmission of a variant allele with a reduced activity. The molecular basis for the low activity is still unknown.     

Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase

The RING finger of BRCA1 confers ubiquitin ligase activity that is markedly enhanced when complexed with another RING-containing protein, BARD1, and is required for the function of this tumor suppressor protein in protecting genomic integrity. Here, we report that co-expression of BRCA1-(1-639) and BARD1 in bacteria can assemble a potent ubiquitin ligase activity. Purified BRCA1-(1-639)*BARD1 stimulated the Ubc5c-mediated monoubiquitination of histone H2A/H2AX in vitro, suggesting a possible role for BRCA1*BARD1 in modifying chromatin structure. Moreover, the truncated BRCA1*BARD1 complex exhibited efficient autoubiquitination activity in vitro capable of assembling non-lysine 48-linked polyubiquitin chains on both BRCA1-(1-639) and BARD1. When co-expressed in cells by transient transfection, the recombinant BRCA1-(1-300).BARD1 complex was found to be associated with polyubiquitin chains, suggesting that BRCA1-(1-300)*BARD1 was ubiquitinated in vivo as well. These results raise the possibility that BRCA1*BARD1 acts to assemble non-lysine 48-linked polyubiquitin chains that may serve as part of a signaling platform required for coordinating DNA repair-related events.     

Analysis of HLA DR2&;DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) Haplotypes in Iranian Patients with Multiple Sclerosis

Multiple sclerosis (MS) is prototype of inflammatory demyelinating disease of the central nervous system .The etiology of MS remains unclear, but according to current data the disease develops in genetically susceptible individuals and may require additional environmental triggers. The human leukocyte antigen (HLA) class II alleles (DRB1*1501, DQA1*0102, DQB1*0602) may have the strongest genetic effect in MS. In this study, the role of these alleles were investigated in 183 Iranian patients with multiple sclerosis and compared with 100 healthy individuals. HLA typing for DRB1*1501, DQA1*0102, DQB1*0602 was performed by polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP) method. The results show that, HLA DR B1*1501 was significantly more frequent among MS patients (46% vs. 20%, PV = 0.0006) but DQA1*0102 haplotype was negatively associated with MS (30% vs. 50%, PV = 0.0049) and no significant association was found with DQB1*0602 and MS patients in comparison with control group (24% and 30%, PV = 0.43). No significant correlation was observed among these alleles with sex, type of disease; initial symptoms, expanded disability status scale (EDSS), as well as age at onset and familial MS. This study therefore indicates that there is no association of above HLA haplotypes with clinical presentation, disease duration, and disability in Iranian patients with MS which is in line with other previous studies in different ethnic groups.     

AM1* parameters for bromine and iodine

Our extension of the AM1 semiempirical molecular orbital technique, AM1*, has been parameterized for the elements Br and I. The basis sets for both halogens contain a set of d-orbitals as polarization functions. AM1* performs as well as other MNDO-like methods that use d-orbitals in the basis, and better than those that rely on an sp-basis. Thus, AM1* parameters are now available for H, C, N, O and F (which use the original AM1 parameters), Al, Si, P, S, Cl, Ti, Cu, Zn, Br, Zr, Mo and I. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.