Detection of rare beta-thalassemia mutations by denaturing gradient gel electrophoresis among Indians

We report four rare beta-thalassemia (thal) mutations, viz. AATAAA --> AACAAA [polyadenylation (poly A) site mutation]. IVS-II-745 (C --> G), codon 121 (G --> T) and IVS-II-1 (G --> A), detected by denaturing gradient gel electrophoresis (DGGE) among Indians. Of these, the poly A site mutation has been found in combination with deletional delta(beta)-thal in one case, and with the IVS-1-5 (G --> C) mutation in another. Two DGGE patterns, corresponding to the same IVS-II-1 (G --> A) mutation, were seen in one family. Framework (FW) analyses in family studies have shown that the poly A site mutation is associated with FW-1, while both the codon 121 (G --> T) and IVS-II-1 (G --> A) mutations are associated with FW-2. Denaturing gradient gel electrophoresis facilitates the screening of rare beta-thal mutations in the diverse Indian population with its many ethnic groups, covering a vast geographic territory.