The novel HLA class I allele, HLA‐B*14:110, identified by next‐generation sequencing

Abstract

The novel HLA‐allele B*14:110, differs from B*14:02:01:01, by one nucleotide substitution, c.T247A in exon 2.

The numbers of identified HLA‐alleles are rapidly increasing since the introduction of sequencing methods such as next‐generation sequencing (NGS) for clinical HLA typing. According to IPD‐IMGT/HLA Database version 3.47 (2022‐01), ¹ a total of 8756 HLA‐B alleles have been identified. At Aarhus University Hospital we annually perform approximately 1000 high resolution HLA typing using NGS.

We report here a novel HLA‐B*14‐allele, now officially named B*14:110. The allele was identified in a patient HLA typed prior to listing for renal transplantation.

The novel allele was determined by NGS applying the Holotype HLA protocol (Omixon, Hungary) and the Illumina MiSeq platform (Illumina, USA). Data was aligned using HLA Twin software 4.4.1 (Omixon). The novel allele was verified with the AllType NGS protocol (One Lambda, USA).

The novel B*14:110 allele has one nucleotide change when compared to the B*14:02:01:01 allele at coding position c.247 T > A in exon 2. This non‐synonymous codon change, TAT > AAT, results in an amino acid substitution from Tyrosine to Asparagine, both of which are neutral polar amino acids (Figure 1A). This novel position is located in the α1 helix of the peptide binding groove, which defines affinity to presented peptides. As the amino acid is located in the α1 helix and not pointing towards the peptide binding site, it is not expected to be directly involved in peptide binding (Figure 1B). ²

FIGURE 1.

Sequence alignment of HLA‐B*14:02:01:01 and HLA‐B*14:110, coding sequences (CDS). Identity to the B*14:02:01:01 allele is shown with dashes (−), the exon boundaries are indicated by pipes (|).

The patient carrying the novel allele had the following extended genotype: HLA‐A*23:01:01:01, 24:02:01G; B*14:110, 35:02:01G; C*02:02:02G, 04:01:01:06; DRB1*01:02:01:01, 11:04:01; DQB1*03:01:01:02, 05:01:01:01; DQA1*01:01:02, 05:05:01:09; DPA1*01:03:01G, 01:03:01G; DPB1*02:01:02:03, 04:01:01:27.

The novel sequence was submitted to GenBank under accession number OM687206. The name B*14:110 has been officially assigned by the WHO Nomenclature Committee for Factors of the HLA System in March 2022. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report, ³ 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.

AUTHOR CONTRIBUTIONS

Marie Quach Lam, Maja Nørgaard: performed the analyses; Maja Nørgaard, Marie Quach Lam, Mira Marie Laustsen: handled and analyzed data; Nicklas Heine Staunstrup, Mira Marie Laustsen, Pernille Koefoed‐Nielsen: wrote the paper; Nicklas Heine Staunstrup, Pernille Koefoed‐Nielsen: supervision.

Laustsen MM, Nørgaard M, Lam MQ, Koefoed‐Nielsen P, Staunstrup NH. The novel HLA class I allele, HLA‐B*14:110, identified by next‐generation sequencing. HLA. 2022;100(5):520‐522. doi: 10.1111/tan.14721

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.