In this study, a novel DRB1 allele was revealed by routine HLA-SBT typing noted for its extensive mismatches to any known DRB1 alleles within the exon 2. Sequences containing the exons 2, 3 of HLA-DRB1, their surrounding introns, and the full-length cDNA of DRB1 were analyzed to determine a possible recombination event. Interestingly, the sequences of entire exon 2 were characterized as DRB3(∗)02:02:01:01/02; while exon 3 were characterized as DRB1(∗)14 like alleles. Further analysis of the sequences using Simplot software suggested that an intergenic recombinant event (i.e. exchange of sequence between non-allelic genes) may have occurred between DRB3(∗)02 allele and DRB1(∗)14 like allele, and the recombination sites are located at intron 1 and the boundary of exon 2 and intron 2 of DRB1. There are 5 CGGGG sequences flanking each side of exon 2 could serve as potential recombination site. Moreover, the full-length cDNA of the novel allele has been identified. The exon 1 and exon 3 to exon 6 share the same sequence as DRB1(∗)14 like alleles. At the mRNA level, the new allele has no significant difference when compared with the other DRB1 allele. This novel recombinant allele is also found to be paternally inherited. In conclusion, this is the first report of a DRB1 and DRB3 intergenic recombination event involving whole exon 2, which generate a new DRB1(∗)14:141.

译文

在这项研究中,通过常规hla-sbt分型揭示了一种新的DRB1等位基因,该分型因其与外显子2内任何已知的DRB1等位基因的广泛错配而闻名。分析包含HLA-DRB1的外显子2、3、它们周围的内含子和DRB1的全长cDNA的序列以确定可能的重组事件。有趣的是,整个外显子2的序列被表征为DRB3(∗)02:02:01:01/02; 而外显子3被表征为DRB1(∗)14类似等位基因。使用Simplot软件对序列的进一步分析表明,可能在DRB3(∗)02等位基因和DRB1(∗)14等位基因之间发生了基因间重组事件 (即非等位基因之间的序列交换),重组位点位于drb1的内含子1和外显子2和内含子2的边界。外显子2两侧有5个CGGGG序列可以作为潜在的重组位点。此外,已经鉴定出新等位基因的全长cDNA。外显子1和外显子3至外显子6与DRB1(∗)14的等位基因共享相同的序列。在mRNA水平上,新等位基因与其他DRB1等位基因相比没有显着差异。这种新的重组等位基因也被发现是父系遗传的。总之,这是涉及整个外显子2的DRB1和DRB3基因间重组事件的首次报道,该事件产生了新的DRB1(∗)14:141。

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