This book reviews the molecular genetics of the thalassemia syndromes, inherited hemoglobin disorders that comprise the commonest mogenic disorders globally. Thalassemias are found in high frequencies in tropical regions corresponding to the malaria belt. Beta thalassemia traits show high HbA2 by HPLC, and ss-globin mutations (commonly point mutations) are detected by using ARMS-PCR, reverse dot-blot analysis and ss-globin gene sequencing. Globally >300 ss globin gene mutations exist, however regional mutations are limited to 5-6 common ones. Alpha globin gene defects can only be identified by molecular tests, the exception being HbH disease that shows golf ball appearance in HbH preparation, pre-integration peaks on HPLC and a fast-moving band on hemoglobin electrophoresis. Multiplex Gap-PCR identifies common alpha-globin gene deletions. Specific PCR across the junction caused by the unequal crossing over can detect alpha-gene triplication. However, heterozygosity or homozygous triplication cant be resolved by this technique. Non-deletional alpha-thalassemia can be characterized by specific alpha-globin gene sequencing. Identification of unusual deletions requires Multiplex Ligation-dependent Probe Amplification. In conclusion, the molecular characterization of human globin gene disorders is required to resolve the phetypically heterogeneous thalassemia syndromes. Molecular analysis is also an important tool to prevent these disorders by offering prenatal screening in regions with a high disease burden.
Postgraduate Institute of Medical Education and Research, Chandigarh, India|Postgraduate Institute of Medical Education and Research, Chandigarh, India
Prashant Sharma, Reena Das
Morgan & Claypool Publishers
Date of Publication
Science & Mathematics: Textbooks & Study Guides
Colloquium Series on Genomic and Molecular Medicine