Stem Cell Transplantation |
1 Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland
2 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
3 Blood Component Expertise, Finnish Red Cross Blood Service, Helsinki, Finland
4 Department of Clinical Chemistry, University of Helsinki, Finland
5 The Finnish Institute for Molecular Medicine (FIMM)
6 Finnish Genome Center, University of Helsinki, Finland
7 The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
8 The Broad Institute of MIT and Harvard, Cambridge, MA, USA
9 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
Correspondence: Hannu Turpeinen, Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland. E-mail:hannu.turpeinen{at}veripalvelu.fi
Background: Matching for HLA genes located on chromosome 6 is required in hematopoietic stem cell transplantation to reduce the incidence of graft-versus-host disease. However, a considerable proportion of patients still suffer from it, obviously due to genetic differences outside the HLA gene region.
Design and Methods: We studied the similarity of almost 4,000 single nucleotide polymorphisms on chromosome 6 between patients receiving hematopoietic stem cell transplantation and their HLA-matched sibling donors.
Results: We observed that as a result of routine HLA matching the siblings in fact shared surprisingly long chromosomal fragments with similar single nucleotide polymorphism genotypes – from 11.65 Mb to 134.66 Mb. The number of genes mapped on these shared fragments varied from 402 to 1,302. Considering the whole chromosome 6, the HLA-matched siblings were apparently identical for 65.2–97.8% of the single nucleotide polymorphisms.
Conclusions: Potentially, genes similar in some transplantation pairs while different in others might have a significant role in determining the outcome after hematopoietic stem cell transplantation.
Key words: hematopoietic stem cell transplantation, graft-versus-host disease, chromosome 6, histocompatibility, genetic similarity.