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Aim To determine the nature and frequency of novel HLA Class I alleles characterised by non-coding polymorphisms. Methods Assign-SBT v3.6+ enables the analysis of SBT sequence data against cDNA and genomic libraries from the IMGT/HLA database. We are in the process of analysing SBT sequence trace da...

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Published in:Human immunology 2012-10, Vol.73, p.116-116
Main Authors: Wirtz, Carla M, Hogan, Hayley M, Alizadeh, Mehdi, Senitzer, David, Gendzekhadze, Ketevan, Iglehart, Brian S, Lind, Curt T, Monos, Dmitrios, Humphreys, Ian, Sayer, David C
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Language:English
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Summary:Aim To determine the nature and frequency of novel HLA Class I alleles characterised by non-coding polymorphisms. Methods Assign-SBT v3.6+ enables the analysis of SBT sequence data against cDNA and genomic libraries from the IMGT/HLA database. We are in the process of analysing SBT sequence trace data from 4 sites in the USA, Australia and Europe from previously typed individuals. Samples with mismatches in non-coding regions of available class I data were recorded for the location and type of sequence mismatch. Results To date, data from 907 samples have been analysed. A total of 118 samples have sequence mismatches, from 1 or more loci, with the IMGT v3.7 allele database. The 118 samples have a total of 21 new alleles with 10 of the 21 alleles (3 × HLA-A alleles, 3 × HLA-B alleles and 4 × HLA-C alleles) being identified in multiple samples across different laboratories. When the new alleles are analysed in conjunction with additional HLA alleles typed in each individual, some of the alleles appear to be unique to specific MHC haplotypes, either as complete extended (or Ancestral) haplotypes or just the HLA-B/C genomic block. The following haplotype specific alleles and predicted haplotypes have been identified to date: A∗ 25:01:01-B∗ 18:01:01new-C∗ 07:01:01-DRB1∗ 15:01:01 A∗ 11:01:01-B∗ 35:01:01-C∗ 04:01:01new1-DRB1∗ 01:03 B∗ 15:01:01new-C∗ 04:01:01 B∗ 44:02:01new-C∗ 07:04 B∗ 44:02:01-C∗ 05:01:01new (These represent a subset of B∗ 44:02:01-C∗ 05:01:01 haplotypes) B∗ 41:01-C∗ 17:01:01new. As distinct from the haplotype specific alleles described above at least one allele, an additional novel C∗ 04:01:01 allele is found on multiple HLA-B/C haplotypes. Conclusions It has been suggested that haplotype matching in HLA matched unrelated bone donor/recipient pairs affects acute GvHD and disease relapse. Matching for the alleles described above provides additional haplotype information. Further studies are required to determine outcomes in donor recipient pairs when the newly described alleles are matched v mismatched.
ISSN:0198-8859
DOI:10.1016/j.humimm.2012.07.230