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

The Rh blood group antigens are encoded by two highly related genes, R HD and RHCE, and the sequence of the common alleles (D, Ce, CE, ce, an d cE) of these genes has been previously elucidated. In this report, R h transcripts and gene fragments have been amplified using polymerase chain reaction from the blood of donors with the C-W+ and C-X+ phenoty pes. 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 spe cificities 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 re sulted in Gln41Arg and Ala36Thr amino acid substitutions in the C-W+ a nd C-X+ polypeptides, respectively. Therefore, although the C-W and C- X specificities behave serologically as if they were allelic, they can not not be considered, stricto sensu, as the products of antithetical allelic forms of the RHCE gene. Based on the C-W-/C-W+ nucleotide poly morphism, a polymerase chain reaction assay useful for diagnosis purpo ses 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 Societ y of Hematology.