Application of discordant sib-pair linkage analysis for mapping minor histocompatibility antigen loci in a novel graft-vs-host-disease model.
Graft-vs-host disease (GVHD) is an adverse effect of allogenic bone marrow transplantation. Although a major cause of GVHD following bone marrow transplantation is incompatibility of major histocompatibility antigen (human leukocyte antigen, HLA) in donor-recipient pairs, the incompatibility of minor histocompatibility antigen (mHa) is known as another cause, especially in HLA-matched donor-recipient pairs. In 1998, Lunetta and Rogus proposed the use of discordant sib-pair (DSP) linkage analysis for detecting mHa and calculated the statistical power using the GVHD model, assuming single mHa locus with multiple alleles. Recently, we proposed a different GVHD model, assuming multiple mHa loci with two alleles (biallelic), considering the single-nucleotide polymorphisms. When the effect of each mHa locus on the occurrence of GVHD is independent, the possible triangle for DSP proposed by Lunetta and Rogus is not optimum, but a new possible triangle, named here as GVHD region, is needed. We evaluated, based on Monte Carlo simulation, the test criteria [log of odds (lod) score cutoffs] and power of DSP using the GVHD region for various parameter sets. The GVHD region showed a higher power than the DSP and entire regions in plausible situations. Our results suggest that the application of GVHD region to DSP is effective for the screening of mHa loci.
Araki
J
J
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. araju.epi@mri.tmd.ac.jp
Ohashi
J
J
Muramatsu
M
M
D008040:Genetic Linkage / Q000235:genetics* / Q000276:immunology*; D005819:Genetic Markers / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D008957:Models, Genetic; D035781:Siblings
D005819:Genetic Markers; D015778:Minor Histocompatibility Antigens