UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://events.um.edu.mt/scisem/
Email: scisem@um.edu.mt
Abstract form
Title: Cis-Trans Interplay Between DNA Sequences 5’ to the Gγ and the β
Globin Genes Among Hb-F-Malta-I Heterozygotes / Homozygotes
and β Thalassemia Homozygotes / Compound Heterozygotes
Presenter: Mr. Joseph Borg B.Sc (Hons) MLS
Contact address: Laboratory of Molecular Genetics, Department of Physiology and
Biochemistry, Biomedical Science Building
Tel: +356 2340 2774
Fax: +356 2134 3535
Email: joseph.borg@biotech.um.edu.mt
Presentation date: 8th January 2006
Abstract
(approximately 200-250 words)
The biochemical mechanisms of globin gene switching remain elusive however considerable insight
is gained by in vivo expression profiling in the context of specific regulatory DNA sequence diversity.
The quantification of normal and abnormal globins of HbF-Malta-I (or a2b2, 117(G19)His>Arg)
heterozygotes which are in tight linkage disequilibrium with Hb Valletta (or a2b2 287(f3)Thr>Pro),
together with haplotyping of homozygotes and heterozygotes including the XMN-I dimorphism in the
Gy promoter and the (AT)xTy polymorphism 5’ to the Beta globin genes had suggested that the XMNI dimorphism was largely inactive in the normal newborn whilst the HbF levels and the proportion of
Gy globin in anemic adult beta-thalassemia homozygotes and compound heterozygotes differed
significantly. Here, we document the occurrence of seven newborns who were heterozygous at three
globin loci permitting quantification by RP-HPLC of the six globin products in the context of genotypic
variation at the XMN-I and (AT)xTy sequences. Results were compared with newborn HbF-Malta-IHb-Valletta heterozygotes and anemic adult beta thalassemia homozygotes/compound
heterozygotes. The globin quantification together with haplotype data were analysed using the
general linear model by SPSS version 12. The data excluded significant effect of the XMN-I
dimorphism alone on relative Gamma/Beta globin gene expression in the newborn. Conversely, the
(AT)xTy with BP1 binding sites of 19 (AT)7T5, 21 (AT)7T7, 23 (AT)9T5, or 25 (AT)11T3, nucleotides in
trans over-ride XMN-I. In contrast, it is the XMN-I dimorphism that over-rides the (AT)xTy diversity in
the anemic adult beta thalassemia homozygotes or compound heterozygotes. The GyFMalta-I/Gyo
ratio of the newborn heterozygotes with Hb F Malta-I and the AyT/AyI ratio of the newborn
heterozygotes with HbF-Malta-I and HbF-Sardinia suggested that the developmental regulation of the
XMN-I site may be subject to cis/trans interplay with the (AT)xTy sequences.