Antenatal Diagnosis of Hemoglobinopathies
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 (RE) 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.
KeywordsPrenatal Diagnosis Preimplantation Genetic Diagnosis Globin Gene Variable Number Tandem Repeat Amplification Refractory Mutation System
- 5.Thein, S. L., Eshari, A., and Wallace, R. B. (1993) The use of synthetic oligonucleotides as specific hybridisation probes in the diagnosis of genetic disorders, in Human Genetic Disease Analysis: A Practical Approach (Davies, K. E., ed.), IRL Press, Oxford, pp. 22–33.Google Scholar
- 19.Losekoot, M., Fodde, R., Harteveld, C. L., Van Heeren, H., Giordano, P. C., and Bernini, L. F. (1991) Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to β thalassaemia. Br. J. Haematol. 76, 269–274.CrossRefGoogle Scholar
- 22.Higgs, D. R. (1993) α-Thalassaemia, in Baillière’s Clinical Haematology. International Practice and Research: The Haemoglobinopathies. (Higgs, D. R. and Weatherall, D. J., eds.) Baillière Tindall, London, p. 117.Google Scholar
- 23.Old, J. M. (1986) Fetal DNA Analysis, in Genetic Analysis of the Human Disease: A Practical Approach (Davies, K. E., ed.) IRL Press, Oxford, UK, p. 1.Google Scholar
- 35.Chakravarti, A., Buetow, K. H., Antonarakis, S. E., Waber, P. G., Boehm, C. D., and Kazazian, H. H. (1984) Non-uniform recombination within the human β-globin gene cluster. Am. J. Hum. Genet. 71, 79.Google Scholar