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Transfusion. 2016 Oct;56(10):2520-2531. doi: 10.1111/trf.13739. Epub 2016 Aug 2.

The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens.

Author information

1
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
2
Red Cross Transfusion Service of Upper Austria, Linz, Austria.
3
Red Cross Blood Service NSTOB, Institute Springe, Springe, Germany.
4
Department of Blood Group Serology and Transfusion Medicine, SALK-Paracelsus Medical University, Salzburg, Austria.
5
Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria.
6
Diagnostic Laboratories, BloodCenter of Wisconsin, Milwaukee, Wisconsin.
7
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland. waf@nih.gov.

Abstract

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.

PMID:
27480171
PMCID:
PMC5499517
DOI:
10.1111/trf.13739
[Indexed for MEDLINE]
Free PMC Article

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