Clinical molecular genetics

Clinical molecular genetics has a relatively brief but spectacular history. In 1970 the first sequencespecific restriction enzyme was discovered and the first gene [yeast alanine transfer ribonucleic acid] was synthesized in vitro. In 1972 the first recombinant DNA molecules were generated and in 1977 the first human gene [human placental lactogen] was cloned. By 1989, 945 human structural genes had been cloned in addition to over 3400 intergenic DNA segments. The first clinical diagnosis using DNA analysis [prenatal diagnosis of sickle cell disease] was made in 1978 and this approach has now become the mainstay of genetic counselling for over 40 important single gene disorders including cystic fibrosis, haemoglobinopathies, thalassaemias, the fragile X syndrome and muscular dystrophies. DNA analysis is also now used for the diagnosis of infectious diseases and is expected to become widely used in predicting risk and prognosis for cancers and other common disorders of adulthood. Molecular genetic techniques are also being used for treatment with either pure protein products or with gene supplementation. In 1977 the first protein product [somatostatin] was made by genetic engineering, followed by insulin in 1979. This approach has already been utilized for a wide variety of hormones and vaccines and in 1990 the first attempts at human supplementation gene therapy for a single gene disorder [adenosine deaminase deficiency] were performed. Gene therapy has also been attempted for treatment of cancer and further therapeutic applications are likely. This article aims to introduce the basic principles of molecular genetics which are common to its now diverse clinical applications and to illustrate some of the applications in modern clinical genetics practice. For more detail on the basic principles and clinical applications the further reading list can be consulted