MICA and MICB microsatellite alleles in HLA extended haplotypes

The present study is a contribution to the definition of the linkage disequ ilibrium relationship of MICA and MICB with adjacent loci and to the charac terization of extended HLA haplotypes. These issues are of importance for t he identification of disease associations and for a better definition of do nor-recipient compatibility in bone-marrow grafts through the typing of hap lospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembr ane exon 5 and in MICB intron 1, was examined in 133 healthy Italian indivi duals previously typed for HLA class I, class II and complement loci and fo r the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage dise quilibria with HLA-B and TNFa were detected in the Italian population for b oth MICA and MICB microsatellite alleles, in spite of the high mutability r ate of the larger MICB alleles. Some strong associations were also detected between MICB and DR-B 1. The strongest associations (P < 0.001, D' > 0.7) were those of MICA-A4 with HLA-B18, B27 and TNFa1, MICA-A5 with HLA-B35, B6 1 and B62, MICA-A5.1 with HLA-B7, B8, B13, B63 and MICB-CA24, MICA-A6 with HLA-B51, MICA-A9 with HLA-B39, B57 and TNFa2, MICB-CA14 with HLA-B14, B27 a nd TNFa1, MICB-CA15 with HLA-B52, TNFa4 and TNFa13, MICB-CA17 with HLA-B7 a nd TNFa11, MICB-CA18 with HLA-B13 and TNFa7, MICB-CA22 with HLA-B57, and MI CB-CA24 with HLA-B8 and TNFa2. From pairwise associations in the random pan el and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Cauc asoid extended haplotypes.