Lack of RH C/E expression in the Rhesus D– phenotype is the result of a gene deletion

Abstract

We have investigated the arrangement of genes in the rare Rh (Rhesus) partial null condition D--. Southern blot and PCR studies under conditions which distinguish the highly homologous RH D and RH C/E genes show that in an Icelandic family with the D-- haplotype at least 85% of the RH C/E gene is deleted. This finding is in contrast to one other published case of this phenotype, where intact RH D and C/E genes were found, and also to the full amorph Rhnull phenotype, where an intact RH C/E gene was found, accompanied by the deletion of the RH D gene typical of Rh D-negative individuals.

Serotype Switching in a Partially Deleted RHD Gene

“…PCR analysis for the presence of RHD. a The 3' end of RHD was assayed for using primers which will prime from exon 10 of RHD but not RHCE [9] b PCR products which may be from exon 5 of either RHCE or RHD were digested with Hindi, which cuts only the RHCE product [13]. UD = Undiges ted product.…”

A Japanese propositus with D-- phenotype characterized by the deletion of both the RHCE gene and D1S80 locus situated in chromosome 1p and the existence of a new CE-D-CE hybrid gene

“…Race and Sanger (1975) remarked on the high incidence of consanguinity in the parents of D--individuals. In an Icelandic family (Blunt et al 1994) and an Italian family (Huang et al 1995), the phenotype was explained by a deletion of the RHCE gene. However, in a French family (Cherif-Zahar et al 1994b), Fig.…”

“…Okubo et al (1983) tested 692,000 Japanese donors and detected 7 donors (0.001%) with the D--phenotype, a frequency of 0.0032 for the D--gene. Recent molecular genetic analyses of the D--variant have shown two genetic forms: the deletion and nondeletion types (Blunt et al 1994;Cherif-Zahar et al 1994b;Huang et al 1995;Huang et al 1996a; Kemp et al 1996).…”

As normal as normal can be?

“…The latter model is supported by mouse knockout studies that have established a link between telomere dysfunction, increased epithelial cancers and radically altered cytogenetic profiles typical of those found in human epithelial cancers 3 . Studies of human primary tumors and epithelial cultures have also supported the idea that telomere dysfunction and its associated bridge-fusion-breakage (BFB) cycles are important in shaping the cancer genome [4][5][6] . But it is not yet known at which stage of tumorigenesis telomere-induced chromosomal instability unfolds.…”

“…But the importance of normal copy-number variation involving large segments of DNA has been largely unappreciated, as only a handful of instances have been reported [3][4][5][6][7][8] . Now, using DNA microarrays (array comparative genomic hybridization) to screen the human genome for changes in copy number, two studies 9,10 report a substantial degree of large-scale copynumber variation (LCV) in the human population.…”