Definition of new alleles of MIC-A using sequencing-based typing

We have sequenced exons 2, 3 and 4 of MIC-A in 23 homozygous cell lines, 22 families and 54 unrelated individuals. This has led to the definition of seven polymorphic positions in exon 2, 13 in exon 3 and 12 in exon 4, yielding a total of 33 different MIC-A allelic specificities, of which 16 have not been described before. The newly defined sequences and those of the alleles defined before were entered into a database of the SCORE program (Helmberg et al., 1998, Tissue Antigens, 51, 587) for comprehensive genotyping analysis. In the tested sample, only one genotype present in two individuals gave rise to an ambiguous genotype. If all possible combinations of the 33 alleles are considered, 10 of 636 combinations are ambiguous. The MICA exon 2, 3 and 4 polymorphism is characterized by diallelic single base exchanges and by a considerable degree of exon shuffling. The majority of heterozygote positions identified are non-synonymous, i.e. five of seven in exon 2, 13 of 13 in exon 3 and eight of 12 in exon 4, suggesting an important function for the MIG-A polymorphism.