Abstract:
As in many other Mediterranean countries, hemoglobinopathies, especially thalassemias pose a major health concern in the Turkish population. Alpha-thalassemias, which may be the most common genetic disorders of human being, result from underproduction of the alpha-globin chains. Reviewing the thalassemia studies at molecular level, it is observed that beta-thalassemia has attracted much more attention than alpha-thalassemia in Turkey. The lack of essential molecular studies in alpha-thalassemia may likely be due to diagnosis difficulty of the alpha-thalassemia symptoms; furthermore, a variety of technical and economical reasons may have prevented the establishment of large-scale population screening programs to detect the alpha-thalassemia mutations in Turkey thus far. A breakthrough in the molecular diagnosis of alpha-thalassemia mutations occured with the advent of PCR technology. The present thesis is focused on the establishment of PCRbased methods and their applications to the detection of the four most common alpha-thalassemia determinants in the Turkish population. The introduction of PCR-based methods for direct and specific detection of the most frequently encountered alpha-thalassemia determinants are very promising in screening programs; because PCR-based methods are faster, more specific, cheaper and simpler than other methods that are used to detect the athalassemia deletions. Making use of two different PCR strategies, 32 Turkish Hb H patients and a-thalassemia carriers were studied in the framework of this thesis. It was observed that the most common genotype in Hb H disease was associated with a combination of 20.5 kb and 3.7 kb deletions. Moreover, the systematic investigation of cord-blood samples from newborn babies revealed the presence of a potential alpha-thal-2 carrier population in Antalya. Due to their relatively common presence in the world, both alpha and beta-thalassemia mutations can be coinherited in the same individual. In this thesis, such a case was observed in a family.
