HLA-B*27:05:25 – a further HLA-B*27:05 allele with a synonymous nucleotide substitution J. Street1 , M. Bengtsson2 , J. Johnson1 , C. Harvey1 & C. Darke1 1 Welsh Transplantation and Immunogenetics Laboratory, Welsh Blood Service, Pontyclun, Wales UK 2 Department of Immunology, Genetics and Pathology, Uppsala University and University Hospital, Uppsala, Sweden Key words: HLA-B*27 ; HLA-B*27:05:25 ; synonymous nucleotide substitution
HLA-B*27:05:25 differs from B*27:05:02 by a single synonymous nucleotide substitution (192C>T) at codon 40 in exon 2. The IMGT/HLA database currently contains 23 HLA-B*27:05 alleles with synonymous nucleotide substitutions, namely B*27:05:02 to B*27:05:24 (1). We have identified a further B*27:05 allele with a synonymous mutation during the sequence-based typing (SBT) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2014, 83, 121–135
of young donors on the Welsh Bone Marrow Donor Registry (2, 3). This allele was named B*27:05:25 by the WHO Nomenclature Committee in September 2013 (accession number HG004400, cell i.d. 15646173) (4). B*27:05:25 is identical to B*27:05:02 in exons 1–4 except for a single mutation at position 192 (C > T) at codon 40 (GCC > GCT – alanine) in exon 2. B*27:05:25 is currently the only B*27 allele to exhibit a change at position 192. 131
The donor, who is of likely North African descent, has the human leukocyte antigen (HLA) type: A*01:03 , A*68:02; B*27:05:25 , B*51:01; C*02:02 , C*16:02; DRB1*08:04 , DRB1*13:02; DQB1*03:01 , DQB1*06:09; and DPB1*02:01 , DPB1*04:01 . Unfortunately, no family members were available to allow the delineation of the B*27:05:25 -bearing haplotype. Accordingly, the donor’s type was analysed using the National Marrow Donor ® Program (NMDP) Bioinformatics group’s resource ‘HaploStats’ (http://www.haplostats.org) based on the methods of Maiers et al. (5). Using the NMDP’s full 2011 dataset and analysis of the ‘African American’ population data suggested that the likely B*27:05 -bearing haplotype is A*68:02 , B*27:05:25 , C*02:02 , DRB1*13:02 and DQB1*06:09 . This single example of B*27:05:25 was identified from a SBT HLA-typed population of 3074 volunteer haemopoietic stem cell donors who are largely north-western European blood donors resident in Wales [B*27:05 carriage frequency (CF) 7.93% and gene frequency (GF), by direct counting, 0.04112]. This indicates a, albeit low precision, B*27:05:25 CF of 0.033% (GF 0.00016) in our local blood donor population. Correspondence
Chris Darke Welsh Transplantation and Immunogenetics Laboratory
132
Welsh Blood Service Pontyclun CF72 9WB Wales UK Tel: 44 (0) 1443 622000 Fax: 44 (0) 1443 622176 e-mail: [email protected] doi: 10.1111/tan.12266
Conflict of interest
The authors have declared no conflicting interests. References 1. Robinson J, Halliwell JA, McWilliam H, Lopez R, Parham P, Marsh SGE. The IMGT/HLA database. Nucleic Acids Res 2013: 41: D1222–7. 2. Pepperall J, Johnson J, Street J, Darke C. Sequence-based HLA typing of 1,000 young donors at registration on the Welsh Bone Marrow Donor Registry. Tissue Antigens 2012: 79: 527–8. 3. Darke C. An overview of the Welsh Bone Marrow Donor Registry: ten years of bone marrow donor provision. Bone Marrow Transplant 2000: 25: 771–7. 4. Marsh SGE. Nomenclature for factors of the HLA system, update September 2013. Tissue Antigens 2013: 82: 485–61. 5. Maiers M, Gragert L, Klitz W. High-resolution HLA alleles and haplotypes in the United States population. Hum Immunol 2007: 68: 779–88.
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2014, 83, 121–135
HLA-B*27:05:25 differs from B*27:05:02 by a single synonymous nucleotide substitution (192C>T) at codon 40 in exon 2. The IMGT/HLA database currently contains 23 HLA-B*27:05 alleles with synonymous nucleotide substitutions, namely B*27:05:02 to B*27:05:24 (1). We have identified a further B*27:05 allele with a synonymous mutation during the sequence-based typing (SBT) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2014, 83, 121–135
of young donors on the Welsh Bone Marrow Donor Registry (2, 3). This allele was named B*27:05:25 by the WHO Nomenclature Committee in September 2013 (accession number HG004400, cell i.d. 15646173) (4). B*27:05:25 is identical to B*27:05:02 in exons 1–4 except for a single mutation at position 192 (C > T) at codon 40 (GCC > GCT – alanine) in exon 2. B*27:05:25 is currently the only B*27 allele to exhibit a change at position 192. 131
The donor, who is of likely North African descent, has the human leukocyte antigen (HLA) type: A*01:03 , A*68:02; B*27:05:25 , B*51:01; C*02:02 , C*16:02; DRB1*08:04 , DRB1*13:02; DQB1*03:01 , DQB1*06:09; and DPB1*02:01 , DPB1*04:01 . Unfortunately, no family members were available to allow the delineation of the B*27:05:25 -bearing haplotype. Accordingly, the donor’s type was analysed using the National Marrow Donor ® Program (NMDP) Bioinformatics group’s resource ‘HaploStats’ (http://www.haplostats.org) based on the methods of Maiers et al. (5). Using the NMDP’s full 2011 dataset and analysis of the ‘African American’ population data suggested that the likely B*27:05 -bearing haplotype is A*68:02 , B*27:05:25 , C*02:02 , DRB1*13:02 and DQB1*06:09 . This single example of B*27:05:25 was identified from a SBT HLA-typed population of 3074 volunteer haemopoietic stem cell donors who are largely north-western European blood donors resident in Wales [B*27:05 carriage frequency (CF) 7.93% and gene frequency (GF), by direct counting, 0.04112]. This indicates a, albeit low precision, B*27:05:25 CF of 0.033% (GF 0.00016) in our local blood donor population. Correspondence
Chris Darke Welsh Transplantation and Immunogenetics Laboratory
132
Welsh Blood Service Pontyclun CF72 9WB Wales UK Tel: 44 (0) 1443 622000 Fax: 44 (0) 1443 622176 e-mail: [email protected] doi: 10.1111/tan.12266
Conflict of interest
The authors have declared no conflicting interests. References 1. Robinson J, Halliwell JA, McWilliam H, Lopez R, Parham P, Marsh SGE. The IMGT/HLA database. Nucleic Acids Res 2013: 41: D1222–7. 2. Pepperall J, Johnson J, Street J, Darke C. Sequence-based HLA typing of 1,000 young donors at registration on the Welsh Bone Marrow Donor Registry. Tissue Antigens 2012: 79: 527–8. 3. Darke C. An overview of the Welsh Bone Marrow Donor Registry: ten years of bone marrow donor provision. Bone Marrow Transplant 2000: 25: 771–7. 4. Marsh SGE. Nomenclature for factors of the HLA system, update September 2013. Tissue Antigens 2013: 82: 485–61. 5. Maiers M, Gragert L, Klitz W. High-resolution HLA alleles and haplotypes in the United States population. Hum Immunol 2007: 68: 779–88.
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Tissue Antigens, 2014, 83, 121–135
