Molecular diversity of the HLA‐C locus in unrelated marrow transplantation

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Abstract
The diversity of HLA‐C exon‐2 alleles in 56 HLA‐A, B, DRB and DQB1‐matched patient‐unrelated marrow donor pairs was examined by non‐cloning polymerase chain reaction‐based sequencing of genomic DNA. This method allows simultaneous analysis of both alleles in heterozygous samples. All Cw5‐positive individuals encoded a sequence which differed from the published Cw*0501 sequence at position 61. Among 82 samples assigned a single antigen by serologic testing, 64 (78%) were heterozygous for two distinct alleles when tested by sequencing. Cw*1202, 1601 and 15 were identified in samples for which no phenotype could be assigned (C “blank”). Finally, 7 of the 56 HLA‐A, B, DRB, DQB1‐matched pairs (12.5%) were mismatched for one or both HLA‐C alleles. We conclude that sequence‐based methods constitute the optimal strategies for typing HLA‐C alleles in the unrelated marrow transplant population.