Molecular analysis of hemoglobinopathies and construction of a database; identification of a novel IVS-II-2 (T-A) mutation

Abstract

Hemoglobinopathies, inherited disorders of the hemoglobin (Hb) molecule, display great molecular and phenotypic diversity. Beta-thalassemia major is considered as the most severe form of hemoglobinopathies and requires life-long blood transfusions to maintain required Hb levels. Although there are improvements in the treatment of beta-thalassemia, there is not any definitive cure yet. Thus, preventive programs must be introduced in order to decrease the probability of affected births. In order to apply effective prenatal diagnosis, it is important to define the molecular basis of a specific population. In the framework of this study, 163 individuals were screened for the mutations in the beta-globin gene. The number of beta-thalassemia alleles was 193; 89 alleles derived from beta-thalassemia minor and 104 were from 52 beta-thalassemia major patients. The methods used were beta-Globin StripAssay, based on reverse dot-blot hybridization and genomic sequencing. By applying these two techniques, all beta-thalassemia alleles were defined, and a total of 24 mutations were described. The results indicate that, unlike other Mediterranean countries, Turkey is very heterogeneous at molecular level. The main cause of this heterogeneity is thought to be the presence of diverse ethnic groups in Turkey, due to its geographical location and rich historical past. Another objective of this thesis was the construction of a database to easily manage the huge amount of patient data in our laboratory. FileMaker Pro provides advantages (short development time, ease of modification and easy access via LAN or World Wide Web) especially for people not involved in bioinformatics, e.g. biologists working in a wet lab. Powerful features, broad platform support, and easy-to-use interface make FileMaker Pro 6 an essential tool for creating and sharing databases.