|
|
 Previous Article | Table of Contents | Next Article 
The Corfu delta beta zero thalassemia: a small deletion acts at a distance
to selectively abolish beta globin gene expression [published erratum
appears in Blood 1988 May;71(5):1509]
AE Kulozik, N Yarwood and RW Jones
Nuffield Department of Clinical Medicine, University of Oxford, John
Radcliffe Hospital, England.
The Corfu delta beta zero thalassemia is characterized by the clinical
picture of thalassemia intermedia. In the homozygous state there is a
complete absence of hemoglobin (Hb) A and Hb A2 and a high level of Hb F. A
DNA fragment containing the gamma and beta globin genes has been cosmid
cloned, and the deletion breakpoint region, the beta globin gene and the
promoter regions of the gamma globin genes sequenced. The deletion removes
7,201 base pairs (bp) containing part of the delta globin gene and
sequences upstream. The beta globin gene contains a G--- -A mutation at IVS
1 position 5. The gamma globin gene promoters are normal. Analysis of the
transcription of the mutated beta globin gene in transfected HeLa cells
shows that normal message is produced at a level of approximately 20%
compared with a normal gene, the remaining 80% being spliced at cryptic
sites in exon 1 and intron 1. This indicates that the mutation in the beta
globin gene is not the sole cause of the absence of Hb A in Corfu delta
beta zero thalassemia. It is concluded that the 7.2 kilobase (kb) of
deleted DNA contains sequences necessary for the normal activation of the
beta globin gene. Possible mechanisms for the effect of the deletion on the
expression of beta and gamma globin genes are discussed.
Volume 71,
Issue 2,
pp. 457-462,
02/01/1988
Copyright © 1988 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Chakalova, C. S. Osborne, Y.-F. Dai, B. Goyenechea, A. Metaxotou-Mavromati, A. Kattamis, C. Kattamis, and P. Fraser
The Corfu {delta}{beta} thalassemia deletion disrupts {gamma}-globin gene silencing and reveals post-transcriptional regulation of HbF expression
Blood,
March 1, 2005;
105(5):
2154 - 2160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Danckwardt, G. Neu-Yilik, R. Thermann, U. Frede, M. W. Hentze, and A. E. Kulozik
Abnormally spliced beta -globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decay
Blood,
March 1, 2002;
99(5):
1811 - 1816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Trifillis, K. Adachi, T. Yamaguchi, E. Schwartz, and S. Surrey
Expression Studies of delta -Globin Gene Alleles Associated with Reduced Hemoglobin A2 Levels in Greek Cypriots
J. Biol. Chem.,
October 25, 1996;
271(43):
26931 - 26938.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P L Campbell, A E Kulozik, J P Woodham, and R W Jones
Induction by HMBA and DMSO of genes introduced into mouse erythroleukemia and other cell lines by transient transfection.
Genes & Dev.,
July 1, 1990;
4(7):
1252 - 1266.
[Abstract]
[PDF]
|
|
|
|
|
