The study of the extended haplotypes of rare HLA-B*2730 allele using microsatellite loci

The aim of the present study was to compare haplotypes of the most frequent B*27 alleles among Croatians (B*2702 and *2705) and the rare B*2730 allele. For this purpose, 37 families with members carrying human leukocyte antigen (HLA)-B27 were selected. All individuals were analysed for eight microsatellites (Msats): D6S2927, short tandem repeat - MHC class I-related gene (STR_MICA), D6S2793, D6S2811, tumor necrosis factor a (TNFa), tumor necrosis factor d (TNFd), D6S273 and D6S1014, while individuals carrying the HLA-B27 specificity were subtyped. Of 39 analysed haplotypes, 20 individuals had B*2702, 15 subjects were positive for the B*2705 allele, the B*2730 allele was found in three haplotypes from different families, while one individual carried the B*2703 allele. HLA-A3 and -DRB1*16 were shared by all three B*2730 haplotypes. The DRB1*16 allele was also observed in the majority of B*2702 haplotypes (76.5%), while HLA-A3 was, after HLA-A2, the second most frequent HLA-A specificity in B*2702 haplotypes. No such correlation was found for the B*2705 haplotypes. Msat analysis showed that B*2730 haplotypes also share the same allele at all tested Msats. The D6S2927, D6S2793, MICA and TNFd Msats were not useful in distinguishing B*2702 and B*2705 alleles because D6S2927-213bp, STR_MICA-179bp, D6S2793-206bp, D6S2811-83bp and TNFd-130bp were detected in almost all cases. Conversely, for the TNFa, D6S273 and D6S1014 loci, haplotypes carrying B*2702 and B*2730 shared a single Msat allele in the majority of cases (TNFa-113bp, D6S1014-134bp and D6S273-134bp), which was not observed for B*2705 haplotypes. In conclusion, the similarity between B*2702 and B*2730 DNA sequences as well as their sharing of the same haplotypic combinations corroborates the proposed mechanism of B*2730 evolution from B*2702 by interallelic recombination.