Structure and expression of the RH locus in the Rh-deficiency syndrome
B Cherif-Zahar, V Raynal, C Le Van Kim, AM D'Ambrosio, P Bailly, JP Cartron and Y Colin
Unite INSERM U76, Institut National de Transfusion Sanguine, Paris, France.
Red blood cell deficiency of Rh proteins is associated with morphologic and
functional abnormalities of erythrocytes and with a chronic hemolytic
anemia of varying severity. Rh-deficiency may be the result of homozygosity
either for a silent allele at the RH locus (Rhnull amorph type) or for a
recessive inhibitor gene(s) at an autosomal locus unlinked to RH locus
(Rhnull regulator and Rhmod). In this report, we investigated the RH locus
structure of Rh-deficient individuals by Southern analysis using cDNA and
exon-specific probes deduced from the recent cloning of Rh genes (CcEe and
D). As expected from family studies indicating that Rhmod and Rhnull
regulator individuals are unable to express Rh antigens but are able to
convey functional Rh genes from one generation to another, no alteration of
the Rh genes was detected in these variants. Although Rhnull of the amorph
type arose by inheritance of a pair of silent alleles at the RH locus, the
general organization of the unique CcEe gene in the genome of the
particular individual under examination was apparently normal and
indistinguishable from a Rh-negative chromosome. More surprisingly, no
mutation could be detected by sequencing the polymerase chain reaction
(PCR)-amplified reticulocyte mRNAs, suggesting that the RH locus of this
patient might be altered in its transcriptional activity. Through
hybridization with exon-specific probes, we were also able to determine the
zygosity for the D gene in DNA samples from individuals of known genotypes;
using this approach, we found that Rhnull regulator variants could be
either of the DD, Dd, or dd genotypes. These findings suggest that the
postulated inhibitor gene(s) can negatively suppress the RH locus
expression from chromosomes carrying either one or two of the Rh genes.
Volume 82,
Issue 2,
pp. 656-662,
07/15/1993
Copyright © 1993 by The American Society of Hematology
