MOLECULAR BACKGROUND OF VS AND WEAK C-EXPRESSION IN BLACKS

BACKGROUND: The Rh system is complex and consists of as many as 45 dif ferent antigens. Red cells of about 25 percent of the black population carry VS, an Rh-system antigen (Rh20), but this antigen is very rare in whites. VS positivity is always associated with a weak expression o f e, and usually also of C. STUDY DESIGN AND METHODS: The RH genes of 11 black VS-positive donors were studied. Transcripts were sequenced f or four VS-positive donors, three of whom had red cells with a weak ex pression of C. In the other donors, only analysis of genomic DNA was c arried out. RESULTS: The occurrence of VS was shown to be related to a single-point mutation in exon 5 of the RHCE gene (cytosine 733 guanin e, leading to the Leu245Val substitution). The presence of this polymo rphism in exon 5 may explain the simultaneously occurring weak e, beca use the E/e polymorphism is located in the same exon. Study of VS-posi tive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors w hose red cells showed a weak expression of C, a hybrid D-CE-D transcri pt was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RH CE gene. No transcripts were encountered carrying DNA markers normally associated with C expression. CONCLUSION: It is therefore postulated that the hybrid gene is responsible for the weak expression of C in th ese individuals. The hybrid gene carried a Leu62Phe substitution, as w ell as the Leu245Val substitution responsible for VS. The gene most pr obably cosegregates with a c allele, encoding Cys16 (normally encoded only by the C allele) and Val245 (responsible for VS antigenicity when encoded by the RHCE gene). This explains the combination of weak expr ession of C and VS positivity that is frequently found in blacks.