DNA Diagnosis of Hemoglobin Mutations

The hemoglobinopathies are a diverse group of inherited recessive disorders that include the thalassemias and sickle cell disease. They were the first genetic diseases to be characterized at the molecular level and, consequently, have been used as a prototype for the development of new techniques of mutation detection. There are now many different polymerase chain reaction (PCR)—based techniques that can be used to diagnose the globin gene mutations, including dot-blot analysis, reverse dot-blot analysis, the amplification refractory mutation system (ARMS), denaturing gradient gel electrophoresis (DGGE), mutagenically separated PCR, gap-PCR, and restriction endonuclease analysis (1 ,2 ). Each method has its advantages and disadvantages, and the particular one chosen by a laboratory to diagnose point mutations depends not only on the technical expertise available in the diagnostic laboratory but also on the type and variety of the mutations likely to be encountered in the individuals being screened.