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Identification of the novel HLA-B*08:181 allele in a volunteer donor for hematopoietic stem cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Univ Hosp, Uppsala, Sweden.ORCID iD: 0000-0002-1037-1601
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Univ Hosp, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Univ Hosp, Uppsala, Sweden.
2019 (English)In: HLA, ISSN 2059-2302, Vol. 93, no 6, p. 485-486Article in journal, Editorial material (Other academic) Published
Abstract [en]

HLA-B*08:181 differs from HLA-B*08:01:01:01 in codon 94, 95, 97 and 99 of exon 3.

In this report, the HLA‐B*08:181 allele, will be described. The novel allele was found in a potential unrelated donor for hematopoietic stem cells. Currently, there are 5590 alleles described according to the IPD‐IMGT/HLA Database1 for the HLA‐B locus.

During routine HLA typing of a potential unrelated bone marrow donor, the initial results obtained from Sanger sequencing (SBTengine, GenDX, Utrecht, The Netherlands) of the HLA‐B locus exons 2 to 4, suggested the presence of HLA B*07:227 and B*08:01:01. By testing with polymerase chain reaction ‐ single specific primer (PCR‐SSP) (Olerup, Stockholm, Sweden) this was not confirmed, instead the presence of the common B*07:02:01 together with a B*08:09/08:12 was suggested, thus indicating the possible presence of a novel HLA allele. To verify the finding, the sample was run on the PacBio long‐range platform (PacBio, Menlo Park, California). DNA was extracted from whole blood with the EZ1 DNA Blood kit (Qiagen, Hilden, Germany). The HLA‐B locus was amplified with B locus specific primers from the 5′ to 3′UTR and the end repair and ligation reaction were performed with the SMRTbell Barcoded Adapter Prep Kit (PacBio). Genotyping was performed using PacBio RSII (PacBio) and the resulting data was analyzed using NGSengine (GenDX). The result gave the clear result of B*07:02:01, the same results as previously, but the software gave the suggestion of HLA B*08:129, with three mismatches in exon 3. Consequently, the new allele shared the beginning of exon three with B*07:227, that is also found in B*57 alleles, thus explaining the Sanger sequencing. Comparison of the genomic full‐length sequence of B*08:129 and B*08:181 showed three nucleotide substitutions in codon 97 (A➔G and G➔T, AGG➔GTG) and 99 (C➔T, TAC➔TAT) in exon 3 (Figure 1). The substitution in codon 97 results in an exchange of Arginine to Valine while the nucleotide exchange in codon 99 does not result in any exchange of amino acid (aa). The chemical differences in the aa substitution from an electrically charged aa to a hydrophobic aa in the peptide binding area of the HLA protein would be considered to affect the protein function, that is, residue 97 is facing pockets C and E in the peptide binding groove.2 However, the serological typing of the potential donor showed a clear HLA B7 and B8 phenotype.

Figure 1

Sequence alignment of exon 3 of HLA‐B*08:01:01:01, HLA‐B*08:129 and HLA‐B*08:181. Dashes (−) indicate nucleotide identity. Codons are indicated by the numbers at the top

The extended HLA typing of the donor was A*01:01:01, 03:01:01; B*07:02:01G, 08:181; C*07:02:01, 07:01:01; DRB1*03:01:01, 15:01:01; DRB3*01:01:02; DRB5*01:01:01, DQA1*05:01:01, 01:02:01; DQB1*02:01:01, 06:02:01; DPA1*01:03:01, 02:01:02; DPB1*01:01:01, 04:01:01.

The genomic sequence of B*08:181 has been submitted to GenBank and the IPD IMGT/HLA Databases (LT707070, HWS10027733).

The name HLA‐B*08:181 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee in April 2017. This follows the agreed policy that subject to the conditions are identified.3 Lists of such new names will be published in the following WHO Nomenclature Report.

Place, publisher, year, edition, pages
2019. Vol. 93, no 6, p. 485-486
Keywords [en]
allele, HLA, HLA B*08:181, sequence-based typing
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-385781DOI: 10.1111/tan.13491ISI: 000467561500009PubMedID: 30773829OAI: oai:DiVA.org:uu-385781DiVA, id: diva2:1325890
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-06-17Bibliographically approved

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Sörman, AnnaBengtsson, Mats

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