Deduced probable HLA haplotypes associated with HLA-C*04:82 found by case analysis of Taiwanese individuals

HLA-C*04:82 is a low incidence HLA-C allele. The aim here is to report the ethnicity of C*04:82 and its associated HLA haplotypes among Taiwanese individuals.

A sequence-based typing method was used to confirm this low incidence allele. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A, HLA-B, and HLA-C loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. The potential unrelated bone marrow stem cell donors in this study were randomized individuals with Taiwanese ethnicity who participated in the Tzu Chi Bone Marrow Donor Registry. The family members in the family part of the study were volunteer blood donors.

The DNA sequence of C*04:82 was identical to C*04:01:01:01 in exons 2, 3, and 4. It differed from C*04:01:01:01 in exon 5 where a segment of nucleotides (CTAGCTGTC) was inserted between residues 969 and 970 of C*04:01:01:01. The insertion of these nucleotides caused a 35 amino acid alteration to the protein sequence of C*04:01:01:01. Three probable HLA haplotypes that were associated with C*04:82 among Taiwanese individuals were deduced. Confirmation of the DNA and protein sequences of C*04:82 and its Taiwanese ethnicity were established in this study.

The ethnicity of the C*04:82 allele and the deduced probable HLA haplotypes associated with the low-incidence C*04:82 allele are of value for reference purposes for HLA testing laboratories. In addition, they can be used by search coordinators to aid the creation of a strategy for finding compatible stem cell donors for patients who carry this uncommon HLA allele.