Gene probes: application to prenatal and postnatal diagnosis of genetic disease

Gene probes can now be used to detect a variety of mutations that produce single-gene disorders. In present clinical practice, restriction endonuclease analysis is used for the prenatal diagnosis of sickle cell anemia, alpha-thalassemia, and beta-thalassemia. Direct detection of the mutation is possible in alpha-thalassemia, where a deletion has usually occurred, and in sickle cell anemia, where the mutation alters the recognition sequence of the restriction endonuclease, Mst II. Indirect detection of beta-thalassemia is based on using normal variations in DNA (DNA polymorphisms) to track normal and affected beta-globin genes in families. This latter kind of analysis is also useful in detecting the phenylalanine hydroxylase genes affected in phenylketonuria and will often be used in disorders where the mutations are unknown. In cases where the mutation is known, direct analysis by use of oligonucleotide probes is a new and important advance. An example of this type of gene detection in a family with classical hemophilia is presented. In addition, with chorion villus biopsy, detection of these inherited diseases is feasible by the 12th week of pregnancy.