Sequence variations in the 5' flanking and IVS-II regions of the G gamma-
and A gamma-globin genes of beta S chromosomes with five different
haplotypes
KD Lanclos, C Oner, AJ Dimovski, YC Gu and TH Huisman
Department of Cell and Molecular Biology, Medical College of Georgia,
Augusta 30912-2100.
We have amplified and sequenced the 5' flanking and the second intervening
sequence (IVS-II) regions of both the G gamma- and A gamma- globin genes of
the beta S chromosomes from sickle cell anemia (SS) patients with
homozygosities for five different haplotypes. The sequencing data, compared
with previously published sequences for the normal chromosomes A and B,
show many similarities to chromosome B for haplotypes 19, 20, and 17, while
haplotypes 3 and 31 are remarkably similar to chromosome A and also similar
to each other. Several unique mutations were found in the 5' flanking
regions (G gamma and A gamma) of haplotypes 19 and 20 and in the IVS-II
segments of the same genes of haplotypes 19, 20, and 17; the IVS-II of
haplotypes 3 and 31 were identical to those of chromosome A. Dot-blot
analyses of amplified DNA from additional SS patients with specific probes
have confirmed that these mutations are unique for each haplotype. The two
general patterns that have been observed among the five haplotypes have
most probably arisen by gene conversion events between the A and B type
chromosomes in the African population. These patterns correlate with high
and low fetal hemoglobin expression, and it is speculated that these and
other yet unknown gene conversions may contribute to the variations in
hemoglobin F and G gamma levels observed among SS patients. In vitro
expression experiments involving the approximately 1.3-kb 5' flanking
regions of the G gamma- and A gamma-globin genes of the beta S chromosomes
with the five different haplotypes failed to detect differences between the
levels of expression, suggesting that the sequence variations observed
between these segments of DNA are not the primary cause of the differences
in hemoglobin F levels among the SS patients.
Volume 77,
Issue 11,
pp. 2488-2496,
06/01/1991
Copyright © 1991 by The American Society of Hematology
