MOLECULAR-BASIS OF THE RHCW (RH8) AND RHCX (RH9) BLOOD-GROUP SPECIFICITIES

The Rh blood group antigens are encoded by two highly related genes, RHD and RHCE, and the sequence of the common alleles (D, Ce, CE, ce, and cE) of these genes has been previously elucidated. In this report, Rh transcripts and gene fragments have been amplified using polymerase chain reaction from the blood of donors with the C-W+ and C-X+ phenotypes. Sequence analysis indicated that the expression of the C-W (Rh8) and C-X (Rh9) antigens are associated with point mutations in the RHCE gene, which provides the definitive evidence that the C-W and C-X specificities are encoded by the same gene as the Cc and Ee antigens. As compared with the common (C-W- and C-X-) transcripts of the RHCE gene, the C-W+ and C-X+ cDNAs exhibited A122G and G106A transitions that resulted in Gln41Arg and Ala36Thr amino acid substitutions in the C-W+ and C-X+ polypeptides, respectively. Therefore, although the C-W and C-X specificities behave serologically as if they were allelic, they cannot not be considered, stricto sensu, as the products of antithetical allelic forms of the RHCE gene. Based on the C-W-/C-W+ nucleotide polymorphism, a polymerase chain reaction assay useful for diagnosis purposes has been developed that detects the presence of the C-W+ allele by the use of an allele-specific primer. (C) 1995 by The American Society of Hematology.