Four categories of gamma-globin gene triplications: DNA sequence comparison
of low G gamma and high G gamma triplications
JZ Liu, JG Gilman, Q Cao, I Bakioglu and TH Huisman
Department of Cell and Molecular Biology, Medical College of Georgia,
Augusta 30912.
The human fetal gamma chains are produced by closely linked G gamma and A
gamma genes, and unequal crossing over between them leads to gamma gene
deletions and triplications. Nine gamma gene triplications from seven
ethnic groups were analyzed for G gamma and hemoglobin F (Hb F) values of
heterozygotes and for the presence of polymorphic XmnI restriction sites 5'
to the gamma genes. Four categories of triplication were found: I had low G
gamma and low Hb F values and lacked XmnI sites 5' to the three gamma genes
[---]. II had high G gamma and slightly elevated Hb F values but was also
[---]. III was similar to II, except that XmnI was [+--]. IV had very high
G gamma and slightly elevated Hb F values, and XmnI was [++-]. One case
each of triplications I and IV were cloned into Charon 35. For both, the
two 5' gamma gene code for G gamma chain, while the 3' gamma gene codes for
A gamma chain. DNA sequencing showed that the unequal crossover occurred
between 472 and 398 base pairs (bp) 5' to the gamma gene Cap sites (- 472
and -398) for the type IV triplication and between -271 and codon 136 for
the type I triplication. In addition, type I had a 4-bp deletion of AGCA
from -225 to -222. The high G gamma values of the type IV triplication are
explained by its -G gamma-G gamma-A gamma-gene arrangement and the XmnI
sites 5' to the G gamma genes. We hypothesize that the low G gamma value of
the type I triplication, which is also -G gamma-G gamma-A gamma-, is due to
inactivation of the middle G gamma gene by the AGCA deletion at -225 to
-222.
Volume 72,
Issue 2,
pp. 480-484,
08/01/1988
Copyright © 1988 by The American Society of Hematology
