Sequence analysis of the MHC class I region reveals the basis of the genomic matching technique.
The genomic matching technique (GMT) improves survival following bone marrow transplantation (BMT) between unrelated donor and recipient pairs correlating with a decrease in incidence and severity of graft-versus-host disease (GvHD). The principles of this technique are based on the duplication and polymorphic characteristics of the major histocompatibility complex (MHC). Specifically, the beta block GMT matches for a 300 kb region that contains the human leukocyte antigen (HLA-B and -C) genes as well as other non-HLA genes such as the natural killer cell receptor ligand PERB11 (MIC). The block contains two large segmental duplications. One results in two PERB11 genes (11.1 and 11.2), the other in two class I genes (HLA-B and -C). With the complete sequencing of the class I region of the MHC in different haplotypes, we can now show that the beta block GMT profiles reflect amplification of the duplicated PERB11 segments and not the duplicated segments containing HLA-B and -C, and yet provide a signature that characterizes the entire block rather than individual loci.
Centre for Molecular Immunology and Instrumentation, University of Western Australia, Western, Nedlands, Australia.
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S
Gaudieri
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Longman-Jacobsen
G K
GK
Tay
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RL
Dawkins
D001483:Base Sequence; D016026:Bone Marrow Transplantation; D017931:DNA Primers; D018076:DNA, Complementary; D005784:Gene Amplification; D020440:Gene Duplication; D005821:Genetic Techniques; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
D017931:DNA Primers; D018076:DNA, Complementary; C089801:HCG9 non-protein coding RNA, human; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated