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The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens
Author(s) -
Srivastava Kshitij,
Polin Helene,
Sheldon Sherry Lynne,
Wagner Franz Friedrich,
Grabmer Christoph,
Gabriel Christian,
Denomme Gregory Andrew,
Flegel Willy Albert
Publication year - 2016
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.13739
Subject(s) - allele , genetics , biology , phylogenetic tree , gene , point mutation , gene conversion , mutation
BACKGROUND 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. STUDY DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.