HLA-A*02:1030:02 is a synonymous variant of HLA-A*02:1030:01, with a T>C substitution at cDNA position 420.

HLA-DPB1*1759:01 differs from HLA-DPB1*02:01:02:01 in exon 4 codon 221 (AGC>ATT).

Identification of 15 novel HLA alleles within haematopoietic cell transplant (HCT) recipients and donors.

ABSTRACTHaematopoietic cell transplantation (HCT) with HLA‐mismatched unrelated donors (MMUD) offers access to curative therapy for patients lacking well‐matched donors. Accumulating evidence suggests that functional matching among allele‐mismatched pairs can significantly influence patient outcomes. Therefore, real‐world data on mismatch frequencies in MMUD‐HCT could provide fundamental information for the assessment of patient risks and donor selection strategies. Here, we analysed HLA matching in 28,376 first unrelated transplants reported to the EBMT Registry with available 6‐locus high‐resolution typing. Mismatches at each locus were quantified and characterised at the allelic, antigenic and functional (antigen‐recognition domain, peptide‐binding motif) levels. 25% of the transplants were performed across one (9/10; n = 6053) or more (< 9/10; n = 1013) high‐resolution mismatches at the five main HLA loci, a proportion that was markedly higher (43.9%) among transplants performed with post‐transplantation cyclophosphamide (PTCy). Median time from diagnosis to transplant was longer for MMUD compared to 10/10 transplants, but this difference decreased over time (14.9 vs. 11.3 months pre‐2011, p = 0.003; 8.1 vs. 7.4 months 2021–2022, p = 0.016). Across transplant eras, single class I mismatches were three times more common than class II mismatches. Conversely, matching for HLA‐DPB1 increased from 15% pre‐2011 to 31% in 2021–2022. The landscapes of allelic mismatches differed markedly between HLA loci. For class II, skewed distributions dominated by frequent combinations result in significantly higher frequencies of functional matching compared to class I in both PTCy and non‐PTCy pairs. Our study constitutes the first large‐scale characterisation of real‐world HLA mismatch frequencies in contemporary unrelated HCT, bearing implications for future clinical outcome studies.

Characterisation of the novel HLA-B*44:561Q allele.

A nucleotide substitution in codon 97 of HLA-B*40:337:01N results in a novel null allele, HLA-B*40:337:02N.

The novel null allele MICB*068N was identified by full-length MICB genotyping.

One novel HLA-DQB1 and one confirmed HLA-DRB1 allele were identified during routine next generation sequencing.

ABSTRACT HLA‐DQB1*06:02:67 differs from HLA‐DQB1*06:02:01:01 by one nucleotide substitution in codon 86 in exon 2.

This study presents the first 4th-field high resolution HLA allele and multi-locus haplotype frequencies from a regional cohort in Western Central Anatolia, including Eskişehir and its surrounding provinces, providing new insights into Turkiye's genetic diversity. Next-generation sequencing (NGS) was used to genotype 138 unrelated healthy individuals for six HLA loci: -A, -B, -C, -DRB1, -DQB1 and -DPB1. MIA FORA NGS FLEX platform was used for genotyping and population genetic analyses were primarily conducted using the HLA-net GENE[RATE] pipeline, with PyPop applied for complementary analyses. Fifty-four HLA-A, 96 HLA-B, 62 HLA-C, 74 DRB1, 45 DQB1 and 33 DPB1 alleles were found at the 4th-field level. A*24:02:01:01 (15.5%), B*51:01:01:01 (6.9%), C*06:02:01:01 (8.7%), DRB1*11:04:01:01 (10.8%), DQB1*03:01:01:02 (18.5%) and DPB1*04:01:01:01 (17.7%) were the most common alleles. The study also identified several rare alleles and haplotypes. This finding highlights the significance of 4th-field resolution in revealing fine-scale diversity. Haplotype analyses observed population-specific combinations with strong linkage disequilibrium, especially between DRB1 and DQB1 (D' = 0.9702). All reported multi-locus haplotypes were validated through significant pairwise LD (standardised residual > 2) between neighbouring loci. For instance, the LD-supported haplotype A*01:01:01:01 ~ B*08:01:01 ~ DRB1*03:01:01:01 (1.45%). When compared to lower-field (2nd-field) data, a considerable amount of sub-allelic diversity was obscured. These results underline the significance of high-resolution HLA genotyping for clinical and population-based applications, as well as Türkiye's distinct immunogenetic structure as a genetic bridge connecting Europe, Asia and the Middle East.