الفهرس 
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Abstract
The haemoglobinopathies are inherited disorders of haemoglobin synthesis that are responsible for significant morbidity and mortality allover the world.
Most common hemoglobinopathies can be classified into:
Structural defects in the hemoglobin molecule. Mutations in the gene for one of the two hemoglobin subunit chains, alpha or beta Sickle hemoglobin exemplifies this phenomenon.
*Diminished production of one of the two subunits of the hemoglobin molecule. Mutations that produce this condition are termed ”thalassemias.”
Sickle-cell disease :
Sickle-cell disease is an autosomal recessive genetic blood disorder, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells’ flexibility and results in a risk of various complications
Thalassemia :
Thalassemia includes disorders affecting the alpha hemoglobin chain genes and the beta hemoglobin chain gene
Alpha Thalassemia :
Alpha thalassemia occurs when one or more of the four alpha chain genes fails to function.
(i) The loss of one gene diminishes the production of the alpha protein only slightly. This condition is so close to normal that it can be detected only by specialized laboratory techniques that. A person with this condition is called a ”silent carrier” because of the difficulty in detection.
(ii) The loss of two genes produces a condition with small red blood cells, and at most a mild anemia. People with this condition look and feel normal. The condition can be detected by routine blood testing, however.
(iii) The loss of three alpha genes produces a serious hematological problem. Patients with this condition have a severe anemia, and often require blood transfusions to survive. The condition is called ”hemoglobin H disease”. Untreated, most patients die in childhood or early adolescence.
(iv) The loss of all four alpha genes produces a condition that is incompatible with life. The gamma chains produced during fetal life associate in groups of four to form an abnormal hemoglobin called ”hemoglobin Barts”. Most people with four-gene deletion alpha thalassemia die in utero or shortly after birth.
Beta Thalassemia :
Beta-thalassemia is a form of thalassemia due to mutations in the Beta globin gene on chromosome 11, inherited in an autosomal recessive fashion.
The severity of the disease depends on the nature of the mutation.
Alleles without a mutation that reduces function are characterized as (β).
Mutations are characterized as (βo) if they prevent any formation of β chains.
Mutations are characterized as (β+) if they allow some β chain formation to occur. (Note that the ”+” in β+ is relative to βo, not β.)
In either case there is a relative excess of α chains, but these do not form tetramers: rather, they bind to the red blood cell membranes, producing membrane damage, and at high concentrations they form toxic aggregates.
Molecular diagnosis of Haemoglobinopathies and its importance :
Over 1,200 different genetic alterations that affect the DNA sequence of globin genes are mainly responsible for the observed clinical heterogeneity. Comprehensive hematological analyses of these mutations provide useful insights for accurately diagnosing thalassemia at the DNA level.
With existing mutation detection technologies, most of which rely on DNA amplification, almost every known sequence variation that leads to an Hb disorder can be identified.
Recent developments in automated high-throughput mutation detection technologies, and the fast pace of discoveries of new globin gene sequence variations dictates the design and implementation of a general screening method with the capacity to identify every globin gene mutation and/or genomic rearrangement possible in both human globin gene clusters and their flanking regions. The construction of globin gene microarrays for resequencing or comparative genomic hybridization could be the solution.