High-resolution HLA genetic diversity in a Northeastern Mexican clinical cohort

The human leukocyte antigen (HLA) region is the most polymorphic region of the human genome. Its allelic and haplotypic diversity varies markedly among populations, making it central to histocompatibility, transplantation, and population genetics. High-resolution data for northeastern Mexico remain scarce. We characterized HLA-A, -B, -C, and -DRB1 in a cohort of 606 unrelated individuals referred for histocompatibility testing between 2019 and 2024, using sequencing-based typing (SBT-Sanger) and next-generation sequencing (NGS) at two-field resolution. Allele and haplotype frequencies, Hardy-Weinberg equilibrium (HWE), the inbreeding coefficient (F _IS), and linkage disequilibrium (LD) were analyzed using Arlequin v3.5.2.2 and R v4.5.2. HLA-A, -B, and -DRB1 conformed to HWE, whereas HLA-C showed a modest but significant deviation (p = 0.038). F _IS was close to zero at every locus (global F _IS = 0.00886), indicating no meaningful inbreeding. LD was significant for all locus pairs and strongest between HLA-B and HLA-C, with D' approaching ±1 for many allelic combinations. HLA-A*03:01-B*07:02-C*07:02-DRB1*15:01 was one of the two most frequent haplotypes (1.24%). Pairwise fixation index (FST) analysis showed the lowest differentiation from admixed populations across the Americas and the greatest from Indigenous populations, most notably the Colombian North Chimila Amerindian population. These findings enhance the immunogenetic characterization of northeastern Mexico and provide a high-resolution regional reference for HLA diversity, with potential relevance to histocompatibility research.