Molecular basis of the Dombrock null phenotype

BACKGROUND: The Dombrock blood group system consists of two antithetical an tigens, Do(a) and Do(b), and three high-incidence antigens, Gregory (Gy(a)) , Holley (Hy), and Joseph (Jo(a)). The null phenotype of the Dombrock blood group system (Do(null)) was identified when it was found that Gy(a-) RBCs also lack Do(a), Do(b), Hy, and Jo(a). STUDY DESIGN AND METHODS: DNA from three Gy(a-) persons was analyzed. PCR p roducts for each of the three DO exons and their flanking intronic regions were sequenced in both directions. The cDNA from two of the people was subj ected to PCR using primers in exon 1 and exon 3, and the products were sequ enced. RESULTS: The Do(null) phenotype is associated with a single nucleotide, mut ation in the acceptor splice site of DO (lVS1-2a >g), which results in outs plicing of exon 2. CONCLUSION: Outsplicing of exon 2 is predicted to cause a -1 frameshift and a premature stop codon. Any product of such a transcript would lack the gl ycosyl-phosphatidylinositol-anchor motif, and RBCs would be devoid of the D o glycoprotein.