Author Correction: Two large deletions extending beyond either end of the RHD gene and their red cell phenotypes.

The authors of the above paper noticed an error in publication. In Results section, under sub-section RHD genetic variations, the deletion nomenclature for Sample 1 was incorrectly given as [NC_000001.11(NG_007494.1):c.(1-15149_1-15153)_(148+3154_148+3158)del].

Two large deletions extending beyond either end of the RHD gene and their red cell phenotypes.

Only two partial deletions longer than 655 nucleotides had been reported for the RHD gene, constrained within the gene and causing DEL phenotypes. Using a combination of quantitative PCR and long-range PCR, we examined three distinct deletions affecting parts of the RHD gene in three blood donors. Their RHD nucleotide sequences and exact boundaries of the breakpoint regions were determined. DEL phenotypes were caused by a novel 18.4 kb deletion and a previously published 5.4 kb deletion of the RHD gene; a D-negative phenotype was caused by a novel 7.6 kb deletion. Examination of the deletion-flanking regions suggested microhomology-mediated end-joining, replication slippage, and non-homologous end-joining, respectively, as the most likely mechanisms for the three distinct deletions. We described two new deletions affecting parts of the RHD gene, much longer than any previously reported partial deletion: one was the first deletion observed at the 5' end of the RHD gene extending into the intergenic region, and the other the second deletion observed at its 3' end. Large deletions present at either end are a mechanism for a much reduced RhD protein expression or its complete loss. Exact molecular characterization of such deletions is instrumental for accurate RHD genotyping.

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

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.