Identification of the HLA‐B*27:277 Allele in Individuals of European Descent and Native American Descent

ABSTRACT

HLA‐B*27:277 differs from HLA‐B*27:05:02:05 by a single substitution in exon 6.

The HLA genes, located in the Major Histocompatibility Complex (MHC) region on the short arm of chromosome 6, code for membrane‐bound proteins essential for immune surveillance. These proteins help the immune system distinguish the body's own cells from foreign ones, a function that is especially critical in the context of organ and tissue transplantation. Notably, HLA genes exhibit the highest degree of genetic variation in the human genome, underscoring their complexity and immunological significance. As of April 2025, according to the IPD‐IMGT/HLA Database release version 3.60, there are 42,772 HLA alleles, of which 10,536 are HLA‐B locus. Of these, 444 are HLA‐B*27 alleles [1]. Based on data from the Allele Frequency Net Database, the frequency of HLA‐B*27 is 38.56% in the USA NMDP Alaska Native or Aleut population [2].

We identified a previously unreported HLA allele, designated HLA‐B*27:277, in an organ donor and recipient of European descent and Native American background. This novel allele was initially detected through high‐resolution HLA typing using Next Generation Sequencing and subsequently validated through confirmatory testing. The complete HLA typing of the donor was assigned as: HLA‐A*01:01, 24:02; ‐B*27:277 , 57:01; ‐C*02:02, 06:02; ‐DRB1*04:01, 07:01; ‐DRB4*01:03, 01:03:01:02N; ‐DQA1*02:01P, 03:03; ‐DQB1*03:01, 03:03; ‐DPA1*01:03, 01:03; ‐DPB1*04:01, 04:01.

Genomic DNA was originally extracted from EDTA‐treated whole blood using the QIAamp spin column method and frozen at −80°C. High‐resolution HLA typing was later carried out utilising the One Lambda AllType Fastplex NGS 11‐loci Flex kit on the Illumina MiniSeq NGS platform. Sequence reads were analysed and alleles assigned using One Lambda's TypeStream Visual (TSV) software version 3.0.0, referencing the IPD‐IMGT/HLA Database version 3.53.0.0. Analysis revealed a potential novel HLA‐B variant, with a unique sequence identified at exon 6, position 1043.

Repeat NGS analysis confirmed the novel allele characterised by a single nucleotide substitution at cDNA position 1043, resulting in an amino acid change at codon 324 in exon 6, where Alanine (GCG) was replaced by Valine (GTG) (Figure 1). The closest matching allele is B*27:05:02:05, differing by a single mismatch in exon 6. In April 2024, the WHO Nomenclature Committee for Factors of the HLA System officially designated this allele as HLA‐B*27:277, in accordance with current nomenclature guidelines [3]. Newly identified sequences that meet established criteria are routinely assigned official names and later compiled in forthcoming WHO Nomenclature Reports.

FIGURE 1.

The DNA sequence of exon 6 of HLA‐B*27:277 is shown in comparison to B*27:05:02:05. HLA‐B*27:277 is identical to B*27:05:02:05 in exons 1, 2, 3, 4, 5 and 7. Identity to the B*27:05:02:05 is shown with dashes (–). There is a one‐base substitution at the codon position 324 in Exon 6, indicated in bold font. The affected codon (boxed) is changed from GCG (Alanine) to GTG (Valine).

The HLA‐B*27:277 sequence has been deposited in the GenBank database and is available under accession number PP318650.

Haplotype analysis could not be performed to establish linkage with B*27:277, as donor and recipient family samples were unavailable, and confidentiality restrictions prevented further investigation.

Author Contributions

David Beaune: acquisition and interpretation of data for the work, drafted the work, final approval, agreement for accountability. Arpit Sharma: acquisition, analysis, and interpretation of data for the work, drafted the work, final approval, agreement for accountability. Kathryn De Koning: acquisition, analysis, and interpretation of data for the work, drafted the work, final approval, agreement for accountability. Abubaker M. E. Sidahmed: lab director and supervisor; primary contact for journal; interpretation of data, revised the work, final approval, agreement for accountability. Sabina Al Agbar: interpretation of the data, drafted the work, final review and approval, agreement for accountability.

Conflicts of Interest

The authors declare no conflicts of interest.

Al Agbar S., De Koning K., Sharma A., Beaune D., and Sidahmed A. M. E., “Identification of the HLA‐B*27:277 Allele in Individuals of European Descent and Native American Descent,” HLA 105, no. 6 (2025): e70287, 10.1111/tan.70287.

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.