Nomenclature for factors of the HLA system, update June 1999. WHO Nomenclature Committee for Factors of the HLA system.
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Biomedical subjects
Publications and source records attributed to S G Marsh.
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This report presents serologic equivalents of 90 HLA-A, 190 HLA-B, and 145 HLA-DRB1 alleles. The equivalents cover over 70% of the presently identified HLA-A, -B, and -DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA-C, DRB3, DRB4, DRB5, and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP), and by individual laboratories. In addition, a listing is provided of alleles that are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serologic typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www.bmdw.org/wmda.
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To further our knowledge of HLA polymorphism in different ethnic populations and to increase the number of full HLA class I typed potential bone marrow donors on the Anthony Nolan Bone Marrow Trust register, HLA-A, -B and -C polymorphism was characterised in 412 Ashkenazi Jewish potential donors. Serological typings and limited molecular analysis was performed for HLA-A and -B, and molecular typings were performed for HLA-C. Gene and haplotype frequencies were calculated using the maximum likelihood method and compared with UK Caucasoid and other Jewish populations. While the specificities identified were in general overlapping with the UK Caucasoid data, a difference in the frequencies of individual specificities was observed. For example, HLA-B62, a common serotype found in the UK Caucasoid population, is almost absent in the Ashkenazim. HLA-A, -C, -B haplotype frequencies also differ between the two populations with A26-Cw*1203-B38 and A24-Cw*04-B35 significant in the Ashkenazim, whilst A1-Cw*07-B8, a common Caucasoid haplotype, was found to be less frequent. Overall the results for the UK Ashkenazi population were most similar to previous reports on Polish/Russian Jews.
Molecular typing for HLA class I was introduced in the 12th International Histocompatibility Workshop. Following a pilot study using three methods, sequence specific oligotyping (SSO), reverse dot blot and amplification refractory mutation system (ARMS)-PCR, the ARMS-PCR method was selected for use. A great advantage of an ARMS-PCR method is that, unlike the other two methods, it can determine whether sequence motifs are in cis or in trans, as ARMS-PCR detects two cis located motifs per reaction using forward and reverse sequence specific primers. Resolution was designed to be low to medium level for HLA-A, -B and -C alleles. Two hundred and fifty class I kits and 83 HLA-A2 subtyping kits were distributed. The A2 subtyping kit used a two round nested PCR system to identify all of the A2 alleles known at the time. Typing results on control DNA samples distributed with both the kits showed a very satisfactory performance. Since the 12th Workshop, the kits have been developed with the addition of new primers and primer mixes to increase the resolution of the test.
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A novel HLA-A*68 allele was identified by reference strand conformation analysis of a DNA sample studied for the International Cell Exchange program. Direct sequencing of HLA-A locus PCR products confirmed the presence of A*6602 and an A*68 allele which differed from A*68011 by two nucleotides at positions 538 and 539. The presence of this sequence motif in this allele which has been named A*6808 was verified by DNA sequencing of full-length A*6808 clones. No other coding differences between A*68011 and A*6808 were identified. The two nucleotide substitutions found in A*6808 effect an amino acid difference in the encoded protein at residue 156 within the peptide binding site which may evoke alloreactive immune response after HLA-A68 mismatched transplants.
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This report presents serologic equivalents of 90 HLA-A, 190 HLA-B and 145 HLA-DRB1 alleles. The equivalents cover over 70% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and by individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serological typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www:bmdw.org/wmda.