title: Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes.
abstract: Rh blood group antigens of the D, C/c, and E/e series are carried by at least three red cell membrane polypeptides encoded by two highly related genes, RHD and RHCE. Homozygous individuals carrying the D--, Dc-, and DCw- gene complexes are characterized by a total or partial lack of expression of the RHCE-encoded antigens. Analysis of the molecular genetic basis of these rare conditions indicates that complete or partial expression defect of Cc/Ee antigens result from different alterations at the RH locus, but not from gross deletions. No rearrangement or mutation of the RHCE gene could be detected in donors homozygous for the D-- complex, suggesting that the lack of the Cc and Ee antigens might result from a reduced transcriptional activity of the RHCE gene. The Dc- and DCw- gene complexes, however, exhibited an important rearrangement of the RHCE gene. Instead of the normal RHCE gene, both variants carried a hybrid RHCE-D-CE gene in which exons 4 to 9 (Dc- complex) and 2 (or 3) to 9 (DCw- complex) of the RHCE gene, respectively, have been substituted by the equivalent region of the RHD gene. These gene conversion events provide an explanation for the well-described abnormal antigen profiles associated with the Dc- and DCw- complexes, like the increased expression of RhD, the reduced expression of RhC/c or RhCw, and the absence of RhE/e.
authors.affiliation: Unité INSERM U76, Institut National de Transfusion Sanguine, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Chérif-Zahar
authors.forename: V
authors.initials: V
authors.lastname: Raynal
authors.forename: A M
authors.initials: AM
authors.lastname: D'Ambrosio
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
authors.forename: Y
authors.initials: Y
authors.lastname: Colin
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005785:Gene Conversion; D005786:Gene Expression Regulation; D005796:Genes; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012204:Rh-Hr Blood-Group System / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012204:Rh-Hr Blood-Group System