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Three deduced probable human-leukocyte-antigen haplotypes associated with HLA-DQB1*03:26 and -DRB1*14:141 from Taiwanese unrelated bone-marrow hematopoietic-stem-cell donors: Two case analyses

Kuo-Liang Yanga, b

a Laboratory of Immunogenetics, Tzu Chi Cord Blood Bank and Buddhist Tzu Chi Marrow Donor Registry, Buddhist Tzu Chi Stem Cells Centre, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
b Department of Laboratory Medicine, Tzu Chi University, Hualien, Taiwan

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Abstract

Objective

HLA-DQB1*03:26 and -DRB1*14:141 are two low-incidence alleles found at the HLA-DQB1 and HLA-DRB1 loci. The objective of this study was to report the ethnicity of DQB1*03:26 and DRB1*14:141, and their deduced probable HLA-associated haplotypes among Taiwanese unrelated bone-marrow hematopoietic-stem-cell donors.

Materials and Methods

A sequence-based typing method was employed to confirm these two low-incidence alleles. Polymerase chain reaction was carried out to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci, and exon 2 of the HLA-DRB1 and HLA-DQB1 loci using group-specific primer sets. The amplicons were then sequenced using a BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions according to the manufacturer's protocols.

Results

The DNA sequence of DQB1*03:26 is most similar to DQB1*03:03:02:01 and DQB1*03:11 in exon 2. It differs from DQB1*03:03:02:01 at residue 136 where the A of DQB1*03:03:02:01 is replaced by the C of DQB1*03:26. This nucleotide exchange leads to an amino-acid alteration in the protein sequence of DQB1*03:03:02:01 at residue 14 where the methionine (M) of DQB1*03:03:02:01 is changed to the leucine (L) of DQB1*03:26. We deduced the probable HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 haplotypes associated with DQB1*03:26 in Taiwanese to be A*02:01-B*40:01-C*03:04-DRB1*08:03-DQB1*03:26 or A*02:01-B*40:01:C*03:04-DRB1*09:01-DQB1*03:26). DQB1*03:26 differs from DQB1*03:11 at residue 266 where the C of DQB1*03:11 is substituted by the A of DQB1*03:26. This nucleotide exchange leads to an amino-acid alteration to the protein sequence of DQB1*03:11 at residue 57 where the amino acid alanine (A) of DQB1*03:11 is replaced by the amino acid, aspartic acid (D), of DQB1*03:26. We also confirmed the DNA and protein sequences of RB1*14:141 and its ethnicity. The probable HLA-A, HLA-B, and HLA-DRB1 haplotypes associated with DRB1*14:141 in Taiwanese may be deduced to be A*02:03-B*15:25-DRB1*14:141.

Conclusion

Information on the ethnicity of the DQB1*03:26 and DRB1*14:141 alleles, and the deduced probable HLA haplotypes associated with the low-incidence alleles that we report here is of value to HLA testing laboratories for reference purposes. In addition, they can be used by stem-cell-transplantation-donor-search coordinators in order to determine a strategy for finding compatible donors in unrelated bone-marrow-donor registries when patients carry these uncommon HLA alleles.

Keywords

Haplotype; Hematopoietic stem cell; HLA; Sequence-based typing; Transplantation


 

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