Approach to the diagnosis of beta-thalassaemia by DNA analysis

Over the last few years, the new techniques of DNA analysis have enabled efficient strategies for the detection and characterisation of the different mutations causing beta-thalassaemia of which a total of 41 have now been characterised. Since the majority of the beta-thalassaemia molecular defects are of the non-deletion type and not directly detectable by Southern blotting, a comprehensive approach to the identification of these mutations entails the use of several different techniques, including direct identification by restriction enzyme analysis and synthetic oligonucleotide probes, indirect identification by linkage analysis to restriction fragment length polymorphisms and globin chain synthesis analysis. As the majority of beta-thalassaemia in each population is accounted for by a few mutants, it should be possible to work out a combination of techniques to directly detect the majority of beta-thalassaemia in a defined population.