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

Antigens of the Rh blood group system are encoded by 2 homologous genes, RH D and RHCE, that produce 2 red cell membrane proteins. The D-negative pheno type is considered to result, almost invariably, from homozygosity for a co mplete deletion of RHD. The basis of all PCR tests for predicting fetal D p henotype 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. RHD psi contains a 37 base pair (bp) i nsert in exon 4, which may introduce a stop codon at position 210, The inse rt is a sequence duplication across the boundary of intron 3 and exon 4, RH D psi contains another stop codon in exon 6, The frequency of RHD psi in bl ack South Africans is approximately 0.0714, Of 82 D-negative black Africans , 66% had RHD psi, 15% had the RHD-CE-D hybrid gene associated with the VS V- phenotype, and only 18% completely lacked RHD, RHD psi is present in ab out 24% of D-negative African Americans and 17% of D-negative South African s of mixed race. No RHD transcript could be detected in D-negative individu als with RHD psi, probably as a result of nonsense-mediated mRNA decay, Exi sting PCR-based methods for predicting D phenotype from DNA are not suitabl e for testing Africans or any population containing a substantial proportio n of people with African ethnicity. Consequently, we have developed a new t est that detects the 37 bp insert in exon 4 of RHD psi. (C) 2000 by The Ame rican Society of Hematology.