Emel Yantır
Turkish Journal of Immunology - 2025;13(3):177-186
Objectives: The resolution level of human leukocyte antigen (HLA) typing critically influences the interpretation of population genetic parameters. This study aimed to quantitatively evaluate the effects of 2-, 4-, and 8-digit typing resolutions on allelic diversity, Hardy-Weinberg equilibrium (HWE), linkage disequilibrium (LD), and asymmetric LD (ALD) in a Central Anatolian population. Materials and Methods: High-resolution next-generation sequencing (NGS)-based HLA typing was performed for six loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1) in 150 unrelated healthy donors. Population genetic analyses were conducted using PyPop v1.2.1 software, and the results were comparatively assessed across 2-, 4-, and 8-digit resolution levels. Results: Higher typing resolution systematically increased allelic richness and revealed hidden heterozygosity. While several loci appeared to conform to HWE at lower resolutions, significant deviations emerged at higher resolutions. Linkage disequilibrium strength increased with resolution, and ALD analysis consistently demonstrated directional dominance between specific locus pairs, reflecting biological hierarchies within haplotypes. Low-resolution typing underestimated allelic diversity, obscured heterozygosity, masked evolutionary signals, and weakened LD, potentially leading to misinterpretations. Conclusion: High-resolution HLA typing, particularly at the 8-digit level, is essential for the accurate interpretation of population genetic parameters, disease association studies, and donor-recipient matching in transplantation. Future studies should focus on developing cost-effective high-resolution typing methods to enhance global accessibility and improve data accuracy in global HLA research.
