Hidden genomic MHC disparity between HLA-matched sibling pairs in hematopoietic stem cell transplantation

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http://hdl.handle.net/10138/234529

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Koskela , S , Ritari , J , Hyvärinen , K , Kwan , T , Niittyvuopio , R , Itälä-Remes , M , Pastinen , T & Partanen , J 2018 , ' Hidden genomic MHC disparity between HLA-matched sibling pairs in hematopoietic stem cell transplantation ' , Scientific Reports , vol. 8 , 5396 . https://doi.org/10.1038/s41598-018-23682-y

Title: Hidden genomic MHC disparity between HLA-matched sibling pairs in hematopoietic stem cell transplantation
Author: Koskela, Satu; Ritari, Jarmo; Hyvärinen, Kati; Kwan, Tony; Niittyvuopio, Riitta; Itälä-Remes, Maija; Pastinen, Tomi; Partanen, Jukka
Contributor: University of Helsinki, Clinicum
Date: 2018-03-29
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/234529
Abstract: Matching classical HLA alleles between donor and recipient is an important factor in avoiding adverse immunological effects in HSCT. Siblings with no differences in HLA alleles, either due to identical-by-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 differences along MHC.
Subject: MAJOR HISTOCOMPATIBILITY COMPLEX
VERSUS-HOST-DISEASE
NONPERMISSIVE HLA-DPB1 DISPARITY
SINGLE-NUCLEOTIDE POLYMORPHISMS
LINKAGE-DISEQUILIBRIUM MAP
DNA-SEQUENCING DATA
MEIOTIC RECOMBINATION
HAPLOTYPE MAP
REGION
GENERATION
3122 Cancers
3111 Biomedicine
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