A rare ancestral HLA-DRB1(∗)15:01̃DQB1(∗)02:01 haplotype and its reversion in the same Western European family

Abstract

The HLA-DR and -DQ loci are close neighbors on chromosome 6 that are highly linked. Many common associations between HLA-DR and DQ-alleles are known, normally transmitted as HLA-DR̃DQ haplotypes from one generation to another. Reports of very recent genetic rearrangements between HLA-DR and -DQ are rarely found in the literature. In Europeans haplotypes containing DRB1(∗)15:01, DQB1(∗)02:01, and DQA1(∗)05:01 have not been reported before. We report the finding of the rare HLA haplotype A(∗)24:02̃C(∗)07:02̃B(∗)07:02̃MICA(∗)008:01̃DRB5(∗)01:01̃DRB1(∗)15:01̃DQA1(∗)05:01̃DQB1(∗)02:01̃DPB1(∗)04:01 in a German stem cell donor with East Frisian ancestry. Our observation suggests a rare ancestral recombination between the DR and DQ loci. In order to investigate this haplotype, we typed 50/74 members of the family encompassing four generations for HLA classes I and II by serological and molecular methods. The rare haplotype was identified in 12 heterozygous carriers. Furthermore, we identified and further characterized a putative crossing over event resulting in its reversion to a common haplotype.

Keywords: HLA; HLA-DR̃DQ haplotypes; Linkage; MHC; Recombination.