The Novel HLA‐DQA1*01:204 Allele Identified in Asian Female Donor by Next‐Generation Sequencing

ABSTRACT

HLA‐DQA1*01:204 differs from HLA‐DQA1*01:02:01:01 by one nucleotide substitution in codon 216 in exon 4.

The HLA genes are the most polymorphic genetic system in the human genome. As of April 2026 [1], a total of 1026 HLA‐DQA1 alleles have been recorded in the IPD‐IMGT/HLA Database version 3.64.0.

We report a novel allele, HLA‐DQA1*01:204, identified during our clinical HLA typing workup of a 22 year‐old Southeast Asian NMDP (National Marrow Donor Program) registered female donor.

HLA genotyping was performed on 11‐loci by next‐generation sequencing (NGS) using the NGS‐Pronto with NGSgo‐IndX Plate III indexing reagents (GenDx, Utrecht, the Netherlands). Sequencing was performed on the MiSeq system (Illumina, San Diego, CA). Allele assignment was initially performed using NGSengine analysis software (GenDx) and subsequently verified by laboratory personnel.

Initial analysis of the HLA‐DQA1 typing showed that there was no perfect match with any known HLA‐DQA1*01 alleles in the IPD‐IMGT/HLA Database version 3.60.0, suggesting the presence of a novel HLA‐DQA1*01 allele, now named DQA1*01:204, with an identical sequence to DQA1*01:02:01:01 from 5′‐untranslated region through 3′‐untranslated region with an exception of a single base mismatch A to G in exon 4, codon 216, ATC to GTC, resulting in the substitution of Isoleucine to Valine at residue 216. The full HLA genotype of the donor was found to be: HLA‐A*02:03, 11:01; ‐B*13:01, 15:25; ‐C*04:03, 04:06; ‐DRB1*12:02, 15:01; ‐DRB3*03:01P; ‐DRB5*01:01; ‐DQA1*01:204, 06:01; ‐DQB1*03:01, 05:02; ‐DPA1*01:03, 01:03; ‐DPB1*03:01, 04:01.

The whole gene sequence of HLA‐DQA1*01:204 was submitted to the GenBank (https://www.ncbi.nlm.nih.gov/genbank/) and IPD‐IMGT/HLA (https://www.ebi.ac.uk/ipd/imgt/hla/) databases and assigned the accessions number PX610256 and HWS10101992, respectively. The name DQA1*01:204 has been officially assigned by the WHO Nomenclature Committee for Factors of the HLA System in March 2026. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report [2], names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report (Figure 1).

FIGURE 1.

The novel HLA‐DQA1*01:204 allele contains a single nucleotide substitution, A→G, compared with HLA‐DQA1*01:02:01:01 at the first base position of codon 216. This results in an amino acid substitution from Isoleucine to Valine. Only codons 215–220 are shown. Dashes indicate identity with the DQA1*01:02:01:01 reference sequence.

Author Contributions

Jasmine Ge contributed to data submission to Gen‐Bank and IPD‐IMGT/HLA Database version 3.60.0, manuscript writing and submission. Vasudha Eravelli performed the NGS amplification. Sharon Austria performed NGS sequencing and initial analysis. Cindy Park and Phillip Ruiz contributed in review of the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. The sequence is freely available in the IPD‐IMGT/HLA Database [1].