Molecular genetic analysis of a hybrid gene encoding Sta glycophorin of the
human erythrocyte membrane
CH Huang, ML Guizzo, M Kikuchi and OO Blumenfeld
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY
10461.
Sta is an antigen of the human MNSs blood group system carried by a variant
glycophorin residing in the erythrocyte membrane. We examined the
structure, organization, and inheritance of Sta gene identified in genomic
DNA from an Oriental family. Southern blotting detected a useful genetic
marker tightly linked to the Sta gene. Differential hybridization and
secondary restriction analyses showed that Sta gene is a fusion hybrid of
delta and alpha glycophorin genes. Genomic mapping by extensive use of
synthetic oligonucleotides, with overlapping sequence specificity, allowed
us to define the delta-alpha junction site and disclose the organization of
the variant gene. The junction point of Sta hybrid gene is encompassed by
an unexpressed exonlike sequence of the delta gene at the 5' site, and an
expressed sequence of the alpha gene spanning codons 59 through 71, at the
3' site. Dosage quantification demonstrated the occurrence of Sta gene as a
single copy in the genome. Blood group inheritance, evaluated by DNA
typing, established the tight linkage of Sta to the alpha M and delta S
genes. The data support a single unequal crossing-over event between
misaligned delta and alpha genes on the homologous chromosomes as the
mechanism for the origin of Sta gene. The Sta gene is similar in overall
structure to another delta-alpha hybrid gene, Dantu, but differs from it in
junction structure, copy number, gene linkage, and antigen specificity.
Volume 74,
Issue 2,
pp. 836-843,
08/01/1989
Copyright © 1989 by The American Society of Hematology