The Molecular Aspects of Thalassemia:
Thalassemias are uniquely
well characterized at the molecular level because much is known about the
structure of the globin genes and behavior in the developing cells (Chao
and Wang, 1996).
The genes encoding for the α
and β chains occur in clusters, the α globin cluster is found on the tip of
chromosome 16 while the β globin gene spans 7kb on the short arm of choromosome
11. The β globin gene cluster is under the control of β locus control region
(BLCR) a major regulatory element located approximately 5 to 20 kb up stream of
the gene (Olivieri, 1999).
The β thalassemia is
inherited as pathologic alleles of one or more globin genes located on
chromosome 11. These lesions range from total deletion to point mutations that
affect every step in the pathway of globin gene expression, transcription,
processing of mRNA precursor, translation of mRNA and post translation
integrity of β polypeptide chain (Forget, 2001).
Over 200 mutations have been
described in the thalassemia phenotype and they have been identified and
classified as β+ or βo depending on whether they reduce
or abolish the production of β globin chains (Honig, 2004).
Figure (1): The b
globin gene cluster. Panel A: The b globin like genes arranged in order in which they are
expressed during development. Panel B: Shows the timing of normal development
switching of human hemoglobin (Olivieri, 1999).
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