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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3662-3668
PLENARY PAPER
RHD gene deletion occurred in the Rhesus
box
Franz F. Wagner and
Willy A. Flegel
From the Abteilung Transfusionsmedizin, Universitätsklinikum
Ulm, and DRK-Blutspendedienst Baden-Württemberg, Institut Ulm,
Ulm, Germany.
The Rh blood group antigens derive from 2 genes,
RHD and RHCE, that are located at
chromosomal position 1p34.1-1p36 (chromosome 1, short arm, region 3, band 4, subband 1, through band 6). In whites, a cde haplotype with a
deletion of the whole RHD gene occurs with a frequency of
approximately 40%. The relative position of the 2 RH genes and
the location of the RHD deletion was previously unknown. A
model has been developed for the RH locus using RHD- and RHCE-related nucleotide sequences deposited in nucleotide sequence databases along with polymerase chain reaction (PCR) and
nucleotide sequencing. The open reading frames of both
RH genes had opposite orientations. The 3' ends of the
genes faced each other and were separated by about 30 000 base pair
(bp) that contained the SMP1 gene. The RHD gene was
flanked by 2 DNA segments, dubbed Rhesus boxes, with a length
of approximately 9000 bp, 98.6% homology, and identical orientation.
The Rhesus box contained the RHD deletion occurring
within a stretch of 1463 bp of identity. PCR with sequence-specific
priming (PCR-SSP) and PCR with restriction fragment length polymorphism
(PCR-RFLP) were used for specific detection of the RHD
deletion. The molecular structure of the RH gene locus explains
the mechanisms for generating RHD/RHCE hybrid alleles and
the RHD deletion. Specific detection of the RHD genotype is now possible.
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RHCE represents the ancestral RH position, while RHD is the duplicated gene
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