Glycophorin He(Sta) of the human red blood cell membrane is encoded by a
complex hybrid gene resulting from two recombinational events
CH Huang, C Lomas, G Daniels and OO Blumenfeld
Lindsley F. Kimball Research Institute, New York Blood Center, NY 10021.
A complex glycophorin (GP) variant of the human red blood cell membrane
exhibiting both He and Sta antigens was characterized at the molecular
level. Restriction mapping identified two novel Msp I fragments derived
from the 5' and 3' portions of the GPHe(Sta) gene, respectively. Genomic
DNA, including exons II-V and their splice junctions, was amplified by
polymerase chain reaction, and the nucleotide sequences were determined.
Comparison with the GPA and GPB sequences showed the presence in GPHe(Sta)
of multiple recombinational breakpoints. In the 5' region of the variant
gene, a sequence covering a portion of exon II to intron 2 had been
transferred from GPA to GPB, resulting in a B-A-B hybrid structure. Such a
gene conversion-like event introduced a number of templated and untemplated
nucleotide replacements and was the direct cause for the expression of the
He antigen. In the 3' region of the variant gene, an unequal crossover from
GPB to GPA took place in the third intron at a recombination site
apparently identical to that observed in the B-A hybrid GPSta type A gene.
These results indicated that GPHe(Sta) occurs as a B-A-B-A hybrid gene,
most likely originating from a two-step mechanism of homologous
recombination. Transcript analysis showed the maturation from the GPHe(Sta)
pre-mRNA of two shortened mRNAs of which the exon III-deleted species
encodes both the He and Sta antigens.
Volume 83,
Issue 11,
pp. 3369-3376,
06/01/1994
Copyright © 1994 by The American Society of Hematology
