Srivastava Kshitij, Polin Helene, Sheldon Sherry Lynne, Wagner Franz Friedrich, Grabmer Christoph, Gabriel Christian, Denomme Gregory Andrew, Flegel Willy Albert
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Red Cross Transfusion Service of Upper Austria, Linz, Austria.
Transfusion. 2016 Oct;56(10):2520-2531. doi: 10.1111/trf.13739. Epub 2016 Aug 2.
The Rh system is the most complex and polymorphic blood group system in humans with more than 460 alleles known for the RHD gene. The DAU cluster of RHD alleles is characterized by the single-nucleotide change producing the p.Thr379Met amino acid substitution. It is called the DAU-0 allele and has been postulated to be the primordial allele, from which all other alleles of the DAU cluster have eventually evolved.
For two novel DAU alleles, the nucleotide sequences of all 10 exons as well as adjacent intronic regions, including the 5' and 3' untranslated regions (UTR), were determined for the RHD and RHCE genes. A phylogenetic tree for all DAU alleles was established using the neighbor-joining method with Pan troglodytes as root. Standard hemagglutination and flow cytometry tests were performed.
We characterized two DAU alleles, DAU-11 and DAU-5.1, closely related to DAU-3 and DAU-5, respectively. A phylogenetic analysis of the 18 known DAU alleles indicated point mutations and interallelic recombination contributing to diversification of the DAU cluster.
The DAU alleles encode a group of RhD protein variants, some forming partial D antigens known to permit anti-D in carriers; all are expected to cause anti-D alloimmunization in recipients of red blood cell transfusions. The DAU alleles evolved through genomic point mutations and recombination. These results suggest that the cluster of DAU alleles represent a clade, which is concordant with our previous postulate that they derived from the primordial DAU-0 allele.
Rh系统是人类中最复杂且多态的血型系统，RHD基因已知有超过460个等位基因。RHD等位基因的DAU簇的特征是单核苷酸变化导致p.Thr379Met氨基酸替换。它被称为DAU-0等位基因，并被假定为原始等位基因，DAU簇的所有其他等位基因最终都从该等位基因进化而来。
对于两个新的DAU等位基因，测定了RHD和RHCE基因所有10个外显子以及相邻内含子区域的核苷酸序列，包括5'和3'非翻译区（UTR）。以黑猩猩为根，采用邻接法建立了所有DAU等位基因的系统发育树。进行了标准血凝试验和流式细胞术检测。
我们鉴定了两个DAU等位基因，DAU-11和DAU-5.1，分别与DAU-3和DAU-5密切相关。对18个已知DAU等位基因的系统发育分析表明，点突变和等位基因间重组促成了DAU簇的多样化。
DAU等位基因编码一组RhD蛋白变体，其中一些形成已知可使携带者产生抗-D的部分D抗原；预计所有这些变体都会在接受红细胞输血的受者中引起抗-D同种免疫。DAU等位基因通过基因组点突变和重组进化而来。这些结果表明，DAU等位基因簇代表一个进化枝，这与我们之前的假设一致，即它们源自原始的DAU-0等位基因。
