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Genomic organization of the glycoprotein D gene: Duffy blood group Fya/Fyb
alloantigen system is associated with a polymorphism at the 44- amino acid
residue
S Iwamoto, T Omi, E Kajii and S Ikemoto
Department of Legal Medicine and Human Genetics, Jichi Medical School,
Tochigi, Japan.
The Duffy blood group antigen has been characterized by its roles on red
blood cells: as a receptor for the malarial parasites and as a promiscuous
receptor for chemokine superfamily. Recently, the Duffy blood group
associated glycoprotein D (gpFy) cDNA has been cloned (Chaudhuri et al:
Proc Natl Acad Sci USA 90:10793, 1993). In this report we describe the
organization of genomic DNA coding for the gpFy and elucidate the molecular
nature of Fya/b polymorphisms. By a Southern blotting analysis probed with
gpFy cDNA, gpFy gene was shown to be composed of three DNA fragments;
1.1-kb Sac I, 1.9-kb EcoRI, and their intervening 47-bp fragments. We
cloned the 1.1-kb Sac I and 1.9- kb EcoRI fragments by inverted polymerase
chain reaction (IPCR) procedure. The promoter region of the gpFy gene was
cloned by IPCR of 1.1-kb Sac I fragment and the 3' flanking sequence was
cloned by IPCR of 1.9 kb EcoRI fragment. The both IPCR products contained
on both side the known gpFy cDNA sequence without introns, as expected.
Although no TATA or CCAAT boxes are present in the promoter sequence,
several transcription factor binding site motifs are contained, including
AP-1, HNF-5, TCF-1, ApoE B2, W-element, H-APF-1, and Sp-1. The 3' flanking
region has two additional polyadenylation signals, other than that used in
the cDNA, and also has an indirect and a direct repeat sequence clustered
with the 5' flanking region. These facts indicate a possibility that the
gpFy gene has been evolved by multiple retrotransposition events. By
comparing the coding area of the gpFy gene in 28 Duffy-positive
individuals, we elucidated that one base change that results in an amino
acid substitution [GA-T(Asp44)-- >GGT(Gly)] is in accordance with the
Fya/Fyb polymorphism. This fact proves that the gpFy cDNA and its gene
described in this report encode the Duffy blood group system.
Volume 85,
Issue 3,
pp. 622-626,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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