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Immunogenetics of hematopoietic stem cell transplantation: the contribution of microsatellite polymorphism studies

Published in International journal of immunogenetics. 2011, vol. 38, no. 5, p. 365-72
Abstract Polymorphisms of short tandem repeats of <10 nucleotides, or microsatellites (Msat), are largely used for post-transplant chimerism analyses in clinical hematopoietic stem cell transplantation (HSCT). Compared to single nucleotide polymorphisms (SNP), they have the advantage of a higher degree of allelic polymorphism and thus a potentially larger degree of informativity. Msat markers contribute to approximately 3% of the human genome and have been highly informative in disease association studies, population genetics, forensic medicine and organ and HSC transplantation. They allowed to expand our knowledge of the haplotypic structure of the HLA complex, including the noncoding sequences in the MHC, and to reach a better characterization of immunological phenotypes. Among the different immunogenetic studies in HSCT patients reviewed here, four Msat loci linked to cytokine genes have been analysed by a number of laboratories as potential candidates markers for HSCT outcome: IFNG, TNFd, IL-10(-1064) and IL-1RN. The low patient numbers and high diversity of clinical parameters account for some heterogeneity of the results. Among the trends starting to emerge from these studies, specific TNFd Msat alleles seem to be associated with acute graft-versus-host disease and mortality. Patient/donor Msat incompatibilities have also been used as surrogate markers to map biologically relevant polymorphisms, with a main focus on MHC-resident genetic variation. High throughput SNP typing and next-generation sequencing technologies will allow acquisition of large-scale genomic data and should allow refined analyses of clinically relevant genotypes in the transplantation settting, although the heterogeneity of the study cohorts will remain an issue. The analysis of Msat polymorphisms may still have a place in functional studies on the impact of Msat diversity in the control of immune response gene expression.
Keywords Cytokines/geneticsHematopoietic Stem Cell TransplantationHumansImmunogenetic PhenomenaMajor Histocompatibility Complex/geneticsMicrosatellite Repeats/genetics/immunologyPolymorphism, Single Nucleotide
PMID: 21816003
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Research group Compatibilité tissulaire et transplantation clinique (562)
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TIERCY, Jean-Marie. Immunogenetics of hematopoietic stem cell transplantation: the contribution of microsatellite polymorphism studies. In: International journal of immunogenetics, 2011, vol. 38, n° 5, p. 365-72. doi: 10.1111/j.1744-313X.2011.01026.x https://archive-ouverte.unige.ch/unige:25367

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Deposited on : 2013-01-10

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