title: Molecular background of VS and weak C expression in blacks.
abstract: BACKGROUND
  The Rh system is complex and consists of as many as 45 different 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 of e, and usually also of C.
  
  
  METHODS
  The RH genes of 11 black VS-positive donors were studied. Transcripts were sequenced for four VS-positive donors, three of whom had red cells with a weak expression of C. In the other donors, only analysis of genomic DNA was carried 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 guanine, leading to the Leu245Val substitution). The presence of this polymorphism in exon 5 may explain the simultaneously occurring weak e, because the E/e polymorphism is located in the same exon. Study of VS-positive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors whose red cells showed a weak expression of C, a hybrid D-CE-D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RHCE gene. No transcripts were encountered carrying DNA markers normally associated with C expression.
  
  
  CONCLUSIONS
  It is therefore postulated that the hybrid gene is responsible for the weak expression of C in these individuals. The hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val substitution responsible for VS. The gene most probably cosegregates with a C allele encoding Cys 16 (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 expression of C and VS positivity that is frequently found in blacks.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
authors.forename: B H
authors.initials: BH
authors.lastname: Faas
authors.forename: E A
authors.initials: EA
authors.lastname: Beckers
authors.forename: P
authors.initials: P
authors.lastname: Wildoer
authors.forename: P C
authors.initials: PC
authors.lastname: Ligthart
authors.forename: M A
authors.initials: MA
authors.lastname: Overbeeke
authors.forename: H A
authors.initials: HA
authors.lastname: Zondervan
authors.forename: A E
authors.initials: AE
authors.lastname: von dem Borne
authors.forename: C E
authors.initials: CE
authors.lastname: van der Schoot
mesh_terms: D000352:Africa, Northern; D044383:Black People / Q000235:genetics*; D015139:Blotting, Southern; D015894:Genome, Human; D006801:Humans; D010641:Phenotype; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013532:Suriname
chemical_list: D012204:Rh-Hr Blood-Group System