G J Cheng1, Y Chen, M E Reid, C H Huang. 1. Laboratories of Biochemistry and Molecular Genetics, Lindsley F. Kimball Research Institue, New York Blood Center, New York, NY 10021, USA.
Abstract
BACKGROUND AND OBJECTIVES: Previously, the Evans antigen (RH37) of the Rh blood group system was shown to be specified by a novel CE-D-CE hybrid gene. We studied further the heterogeneity of Evans and report here its new molecular type resulting from a novel intraexon fusion event on the background of D. and D-- complexes. MATERIALS AND METHODS: A white family with 2 Evans+ and 2 Evans- members was analyzed by serological methods and molecular techniques. RESULTS: The Evans+ proband (JD) typed D+C-c-E-e- and showed a partial loss of RHCE but an increased dose of RHD on DNA blots. On sequencing of Rh cDNAs, a normal D and 3 hybrid transcripts were detected. The D-CE hybrid is characterized by a single breakpoint located in exon 6. The CE-D hybrid derived its exon 1 (or 1 and 2) from RHCE and exons 2-10 (or 3-10) from RHD. The CE-D-CE hybrid had its internal exons 2-7 (or 3-7) from RHD. Family studies showed that the D-CE and CE-D hybrids were linked and cotransmitted from JD to his son, whereas RHD and CE-D-CE hybrid were transmitted from JD to his daughter. CONCLUSION: In this family, Evans is specified by the novel D-CE intraexon fusion gene which occurs in cis to CE-D and trans to CE-D-CE interexon fusion genes. The observed large duplication of RHD reflects a convergent mosaicism underlying the enhancement of D and ablation of CcEe antigens.
BACKGROUND AND OBJECTIVES: Previously, the Evans antigen (RH37) of the Rh blood group system was shown to be specified by a novel CE-D-CE hybrid gene. We studied further the heterogeneity of Evans and report here its new molecular type resulting from a novel intraexon fusion event on the background of D. and D-- complexes. MATERIALS AND METHODS: A white family with 2 Evans+ and 2 Evans- members was analyzed by serological methods and molecular techniques. RESULTS: The Evans+ proband (JD) typed D+C-c-E-e- and showed a partial loss of RHCE but an increased dose of RHD on DNA blots. On sequencing of Rh cDNAs, a normal D and 3 hybrid transcripts were detected. The D-CE hybrid is characterized by a single breakpoint located in exon 6. The CE-D hybrid derived its exon 1 (or 1 and 2) from RHCE and exons 2-10 (or 3-10) from RHD. The CE-D-CE hybrid had its internal exons 2-7 (or 3-7) from RHD. Family studies showed that the D-CE and CE-D hybrids were linked and cotransmitted from JD to his son, whereas RHD and CE-D-CE hybrid were transmitted from JD to his daughter. CONCLUSION: In this family, Evans is specified by the novel D-CE intraexon fusion gene which occurs in cis to CE-D and trans to CE-D-CE interexon fusion genes. The observed large duplication of RHD reflects a convergent mosaicism underlying the enhancement of D and ablation of CcEe antigens.