title: The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens.
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.
  
  
  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.
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.
authors.forename: Helene
authors.initials: H
authors.lastname: Polin
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Sherry Lynne
authors.initials: SL
authors.lastname: Sheldon
authors.affiliation: Red Cross Blood Service NSTOB, Institute Springe, Springe, Germany.
authors.forename: Franz Friedrich
authors.initials: FF
authors.lastname: Wagner
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine, SALK-Paracelsus Medical University, Salzburg, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Grabmer
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.|Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Diagnostic Laboratories, BloodCenter of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Gregory Andrew
authors.initials: GA
authors.lastname: Denomme
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland. waf@nih.gov.
authors.forename: Willy Albert
authors.identifier: http://orcid.org/0000-0002-1631-7198
authors.initials: WA
authors.lastname: Flegel
mesh_terms: D000328:Adult; D000349:Africa; D000483:Alleles; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D017354:Point Mutation; D011247:Pregnancy; D011995:Recombination, Genetic; D012204:Rh-Hr Blood-Group System / Q000235:genetics*
chemical_list: C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen