Characterization of the MICA polymorphism by sequence-specific oligonucleotide probing

Abstract

 A large number of diseases occur in association with specific HLA-B or –C alleles. Recently a new gene, termed major histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown, but, it is structurally related to HLA class I genes, is polymorphic, and is potentially associated with several diseases. Some DNA-based techniques have previously been described to type for MICA including sequencing and single-strand conformational polymorphism. In this paper we describe the application of sequence-specific oligonucleotide probe based typing for the analysis of the MICA gene. We used a set of 30 oligonucleotide probes to screen for the polymorphisms in exons 2, 3, and 4, which account for the 16 known alleles. We report here the typing results of MICA for 103 B-cell lines that have been well characterized for HLA and describe the linkage disequilibrium between MICA and HLA-B. Unequivocal MICA typing was achieved for 85 of the 103 cells tested, 6 cells gave ambiguous MICA types, and a further 12 cells showed patterns consistent with them expressing at least one new MICA allele.