Matching classical HLA alleles between donor and recipient is an important factor in avoiding adverse
immunological efects in HSCT. Siblings with no diferences in HLA alleles, either due to identicalby-state or identical-by-descent status, are considered to be optimal donors. We carried out a
retrospective genomic sequence and SNP analysis of 336 fully HLA-A, -B, -DRB1 matched and 14
partially HLA-matched sibling HSCT pairs to determine the level of undetected mismatching within the
MHC segment as well as to map their recombination sites. The genomic sequence of 34 genes locating
in the MHC region revealed allelic mismatching at 1 to 8 additional genes in partially HLA-matched
pairs. Also, fully matched pairs were found to have mismatching either at HLA-DPB1 or at non-HLA
region within the MHC segment. Altogether, 3.9% of fully HLA-matched HSCT pairs had large genomic
mismatching in the MHC segment. Recombination sites mapped to certain restricted locations. The
number of mismatched nucleotides correlated with the risk of GvHD supporting the central role of full
HLA matching in HSCT. High-density genome analysis revealed that fully HLA-matched siblings may
not have identical MHC segments and even single allelic mismatching at any classical HLA gene often
implies larger genomic diferences along MHC.