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Molecular basis of the altered antigenic expression of RhD in weak D(Du) and RhC/e in RN phenotypes.
- Source :
-
Blood [Blood] 1996 Jun 01; Vol. 87 (11), pp. 4853-61. - Publication Year :
- 1996
-
Abstract
- The RH blood group locus is composed of two sequence-related genes, RHD and RHCE, encoding the D, Cc, and Ee antigens in common Rh-positive phenotypes. In this report, we have analyzed the molecular basis of Rh antigens expression in weak D (Du) and RN donors, in whom there is a severe reduction of the D and C/e antigens, respectively. Genomic and transcript analysis of three unrelated low-grade weak D (Du) variants indicated that the very low expression of the D antigen is not the result of rearrangement or mutation in the coding sequence of the RHO gone. Accordingly, weak D (Du) erythrocytes should carry a normal RhD polypeptide, which is in agreement with the observation that these variants never produce anti-D antibodies. Comparative polymerase chain reaction analysis showed a lower steady-state level of RhD transcripts in weak D (Du) reticulocytes, as compared with normal RhD-positive controls, thus providing direct evidence that the difference between the D antigen of D-positive and weak D (Du) red blood cells is quantitative only. Conversely, analysis of the molecular genetic basis of the RN phenotype Indicated that the severely decreased expression of the RhC and Rhe antigens in three variants is associated with a qualitative alteration identified as a segmental DNA exchange between the RHCE and RHD genes. These genomic rearrangements, which resulted in hybrid RhCe-D-Ce proteins expressing the low frequency Rh32 but not the high incidence Rh46 antigens, involved either axon 4 alone or both exons 3 and 4. These findings show that an identical phenotypical alteration of Rh antigens (reduced expression) may result either from a quantitative or a qualitative alteration of the RH genes expression.
- Subjects :
- Alleles
Base Sequence
Exons genetics
Genetic Variation
Humans
Models, Molecular
Molecular Sequence Data
Phenotype
Polymerase Chain Reaction
Recombination, Genetic
Rh-Hr Blood-Group System chemistry
Transcription, Genetic
Gene Expression Regulation
Rh-Hr Blood-Group System biosynthesis
Rh-Hr Blood-Group System genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 87
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 8639859