UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://www.um.edu.mt/events/scisem/
Email: scisem@um.edu.mt
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Abstract
The Effects of Trans-Regulatory Loci on Globin Gene Control
Dr Amal Mohammed Daw
Laboratory of Molecular Genetics
00356 2340 2774
00356 2134 3535
daw_amel@yahoo.com
12th December 2011
Approximately 200-250 words. Please email to scisem@um.edu.mt.
Augmenting the level of foetal haemoglobin (HbF) in sickle cell disease or β-thalassemia
patients would greatly ameliorate the symptoms associated with these diseases. This can
only be achieved by first understanding the genetic switch from foetal to adult haemoglobin
that is commonly referred to as γ to β globin gene switching. In this study a combination of
clinical research coupled with basic research was carried out. 190 β-thalassemia
heterozygotes were identified by the screening program carried out by the Laboratory of
Molecular Genetics, University of Malta. A complete blood count accompanied all blood
samples to the laboratory. HbF and HbA2 measurements were conducted using a HighPressure Liquid Chromatography. DNA sequencing of all samples was performed for the β
globin gene and its promoter. The results showed the commonly encountered β
thalassaemia alleles in the Maltese population; these being IVSI-6C, IVSI-110A, Codon 39
T, IVSII-1A and other rare ones as well including a deletion of 2 nts in the β globin gene
coding sequence identified for the first time in Malta. The -158 CT 5’Gγ globin SNP
genotyping was performed by XmnI restriction enzyme digest. Three polymorphisms
(rs766432, rs11886868 and rs4671393) in BCL11A and another three (rs4895441,
rs28384513 and rs9399137) in MYB were genotyped using Real Time PCR. There was a
positive association between the MYB and HbF levels in β0 Codon 39 heterozygotes whilst
not with other β thalassaemia alleles. Only one dimorphism in BCL11A was associated with
higher HbF levels in β thalassaemia heterozygotes. As exemplified by EKLF in previous
work carried out in the laboratory, and other transcription factors such as BCL11A and MYB
in this study are thought to play a significant role in promoter-specific gene activation and
warrant further investigation regarding their role in globin switching.