An Insight from Western Central Anatolia on the Common and Well-Documented HLA Catalogs: A Single-Center Pilot Analysis

This pilot study aims to demonstrate that global Human Leukocyte Antigen (HLA) catalogs do not adequately represent local genetic diversity and, consequently, to emphasize the need for a national “Common and Well-Documented” (CWD) allele catalog based on high-resolution data. Rather than aiming to establish definitive population-level allele frequencies, this study was designed as a pilot analysis to enable a comparative evaluation of regional HLA data within the framework of existing global CWD/CIWD catalogs. The HLA-A, -B, -C, -DRB1, and -DQB1 loci of 142 unrelated healthy donors from Eskişehir and neighboring provinces were typed at high resolution (8-digit) using Next-Generation Sequencing (NGS) technology. Allele frequencies were calculated using with Pypop software, and the obtained profile was compared with the global CIWD 3.0.0 catalog and national catalogs of countries such as Germany, China, Russia, and Brazil. Despite sharing common alleles with European (EU) and Middle East/North Africa (MENA) populations, our study population exhibited a unique genetic profile. The most striking finding was that 76 out of 228 alleles at the 8-digit level were not represented in the EU and MENA reference datasets of the CIWD 3.0.0 catalog. 8-digit analysis revealed dominant subtypes such as A*02:01:01:01 within the G-group, highlighting potential classification errors in global catalogs and the importance of local data. The study concludes that existing international catalogues do not fully represent the genetic structure of a part of the Turkish population. This represents a significant gap for clinical applications like transplant matching and disease risk assessment. The findings strongly emphasize the strategic necessity of establishing a high-resolution National HLA CWD/CIWD Catalog that reflects Türkiye's genetic diversity, serves as a reference for clinical laboratories, and optimizes strategies for bone marrow banks.