title: The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype.
abstract: Antigens of the Rh blood group system are encoded by 2 homologous genes, RHD and RHCE, that produce 2 red cell membrane proteins. The D-negative phenotype is considered to result, almost invariably, from homozygosity for a complete deletion of RHD. The basis of all PCR tests for predicting fetal D phenotype from DNA obtained from amniocytes or maternal plasma is detection of the presence of RHD. These tests are used in order to ascertain the risk of hemolytic disease of the newborn. We have identified an RHD pseudogene (RHD psi) in Rh D-negative Africans. RHDpsi contains a 37 base pair (bp) insert in exon 4, which may introduce a stop codon at position 210. The insert is a sequence duplication across the boundary of intron 3 and exon 4. RHDpsi contains another stop codon in exon 6. The frequency of RHDpsi in black South Africans is approximately 0.0714. Of 82 D-negative black Africans, 66% had RHDpsi, 15% had the RHD-CE-D hybrid gene associated with the VS+ V- phenotype, and only 18% completely lacked RHD. RHDpsi is present in about 24% of D-negative African Americans and 17% of D-negative South Africans of mixed race. No RHD transcript could be detected in D-negative individuals with RHDpsi, probably as a result of nonsense-mediated mRNA decay. Existing PCR-based methods for predicting D phenotype from DNA are not suitable for testing Africans or any population containing a substantial proportion of people with African ethnicity. Consequently, we have developed a new test that detects the 37 bp insert in exon 4 of RHDpsi. (Blood. 2000; 95:12-18)
authors.affiliation: Bristol Institute for Transfusion Sciences, Bristol, England.
authors.forename: B K
authors.initials: BK
authors.lastname: Singleton
authors.forename: C A
authors.initials: CA
authors.lastname: Green
authors.forename: N D
authors.initials: ND
authors.lastname: Avent
authors.forename: P G
authors.initials: PG
authors.lastname: Martin
authors.forename: E
authors.initials: E
authors.lastname: Smart
authors.forename: A
authors.initials: A
authors.lastname: Daka
authors.forename: E G
authors.initials: EG
authors.lastname: Narter-Olaga
authors.forename: L M
authors.initials: LM
authors.lastname: Hawthorne
authors.forename: G
authors.initials: G
authors.lastname: Daniels
mesh_terms: D000595:Amino Acid Sequence; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D001782:Blood Donors; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D005260:Female; D005869:Ghana; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D000071058:Huntingtin Protein; D007231:Infant, Newborn; D007438:Introns; D008145:Louisiana; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011544:Pseudogenes / Q000235:genetics; D011993:Recombinant Fusion Proteins; D012091:Repetitive Sequences, Nucleic Acid; D012204:Rh-Hr Blood-Group System; D012307:Risk Factors; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013019:South Africa; D014158:Transcription, Genetic; D015030:Zimbabwe; D001741:Black or African American
chemical_list: D006023:Glycoproteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C066468:RHCE protein, human; D011993:Recombinant Fusion Proteins; D012204:Rh-Hr Blood-Group System; C117760:RhD fusion protein, human; C026410:Rho(D) antigen