ALLELIC VARIANTS OF THE HUMAN MHC CLASS-I CHAIN-RELATED B-GENE (MICB)

The human major histocompatibility complex (MHC) is located within a 4 megabase segment on chromosome 6p21.3. Recently, a highly divergent M HC class I chain-related gene family, MIC was identified within the cl ass I region. The MICA and MICB genes in this family have unique patte rns of tissue expression. The MICA gene is highly polymorphic, with mo re than 20 alleles identified to date. To elucidate the extent of MICB allelic variations, we sequenced exons 2 (alpha 1), 3 (alpha 2), 4 (a lpha 3), and 5 (transmembrane) as well as introns 2 and 4 of this gene in 46 HLA homozygous B-cell lines. We report the identification of el even alleles based on seven non-synonymous, two synonymous, and four i ntronic nucleotide variations. Interestingly, one allele has a nonsens e mutation resulting in a premature termination codon in the alpha 2 d omain. Thus, MICB appears to have fewer alleles than MICA, not unlike the allelic ratio between the HLA-C and -B loci. A preliminary linkage analysis of the MICB alleles with those of the closely located MICA a nd HLA-B genes revealed no conspicuous linkage disequilibrium between them, implying the presence of a potential recombination hotspot betwe en the MICB and MICA genes.