HLA system nomenclature and discovery of novel allelic variants in the Kazakh population

Abstract

The human leukocyte antigen (HLA) system is among the most genetically diverse in humans, encompassing over 220 genes that encode immune proteins essential for transplant compatibility, immune regulation, and disease susceptibility. This review outlines the fundamentals of HLA nomenclature, standardized by the World Health Organization (WHO) and curated in the IPD-IMGT/HLA database. We describe the gradual improvements in HLA typing methods, ranging from serological assays to molecular-based techniques, including Sanger sequencing and next-generation sequencing (NGS), as well as interpretation software, and evaluate their strengths and limitations in allele discovery. We discuss allelic variants of HLA genes, methods for sequencing HLA alleles, and their variants. Additionally, we report the identification of four novel HLA alleles in the Kazakh population: DQB1*03:82, C*06:256, B*13:150, and A*32:95. All four alleles feature non-synonymous substitutions within peptide-binding domains, suggesting potential immunological relevance. Comparative analysis reveals that NGS enhances allele detection efficiency by 2.8-fold compared to Sanger sequencing (one novel allele per 635 typings vs. 1,773). These findings demonstrate the significant HLA diversity present in Central Asian populations, which remain underrepresented in global databases. The identification of population-specific alleles reveals critical gaps in international donor databases, underscoring the urgent need to expand HLA profiling in ethnically diverse regions to improve transplant outcomes and advance personalized immunotherapy.