Expanded Allelic Diversity of Non‐Classical HLA Class I and MIC Loci Identified Using Full‐Gene Hybrid Capture–Based Next‐Generation Sequencing

ABSTRACT Non‐classical HLA Class I genes ( HLA‐E , ‐F , ‐ G , ‐ H ) and MHC‐related genes ( MICA , MICB ) regulate NK cell function and immune tolerance, yet their allelic diversity remains underexplored. Using capture‐enriched full‐gene sequencing of 943 healthy US transplant donors, we identified 26 novel alleles across HLA‐E (2), HLA‐F (6), HLA‐G (4), HLA‐H (5), MICA (3), and MICB (6). Each novel allele was identified in a single individual and differs from its closest known allele by a single‐nucleotide polymorphism within the coding region. In addition, we confirmed the recently described allele HLA‐G*01:01:33 in 16 unrelated donors. In all cases, it consistently co‐segregated with HLA‐A*34:01:01 , HLA‐F*01:01:01 and HLA‐H*02:27 , supporting the presence of a conserved haplotype. These findings expand the catalogue of non‐classical HLA and MIC alleles, highlighting capture‐enriched full‐gene sequencing as a powerful tool for comprehensive immunogenetic profiling.