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

Abstract

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.

Nonfrequent but well‐documented, rare and very rare HLA alleles observed in the Croatian population

“…Our intention was to provide additional information about the presence of these nonfrequent, rare or very rare HLA alleles in the Croatian population and to motivate other laboratories in this part of Europe to report their data, in this way forming a database which could be used to answer those questions. An example of such a nonfrequent allele is B*27:30 , which was found in the Slovenian population in 2006 and shortly afterwards observed in our population in a patient with ankylosing spondylitis (AS), as well as among a few healthy individuals . Currently, there is still no available data about the presence and rank of the B*27:30 allele/haplotype due to the fact that there were no reports (with the exceptions of the Croatian minority in DKMS and Switzerland‐Geneva population) of its presence in other populations in the last few years (http://www.allelefrequencies.net) .…”

HLA‐A, HLA‐B and HLA‐DRB1 allele and haplotype diversity among volunteer bone marrow donors from Croatia

“…The highest disproportion in a haplotype frequency between CBMDR and ZKRD was observed for haplotype A*02:01‐B*27:02‐DRB1*16:01 placed in the seventh position in CBMDR as opposed to the 49th position in ZKRD. This finding supports our previously reported results about a very strong linkage disequilibrium found between B*27:02 allele and DRB1*16:01 allele in our population which leads to a much higher frequency of the above‐mentioned haplotype than it would otherwise be expected (Grubic et al ., ). The frequency of this haplotype found among Croats is so far surpassed only by the frequency observed among Bulgarians (2.7%; Ivanova et al ., ; Gonzales‐Galarza et al ., ).…”

Progress in spondylarthritis. Progress in studies of the genetics of ankylosing spondylitis

“…For some subtypes, however there is evidence of differential strength of association with AS. AS has been reported to occur with the following subtypes: B*2701, B*2702 [11], B*2703 [12], B*2704 [13], B*2705 [11], B*2706 [14], B*2707 [15], B*2708 [15], B*2709 [16], B*2710 [17], B*2714 [18], B*2715 [18], B*2719 [19] and B*2730 [20]. …”