Molecular diagnosis of genetic disease

DNA-based testing is becoming possible for an increasing number of hereditary diseases as the responsible genes are mapped to individual chromosomes and then isolated and characterized. The strategy for each test depends on the heterogeneity of mutations commonly causing the disease, the distribution of the mutations in the population and the frequency of new mutations. In many cases, interpretation of the test result requires a comparison with relatives known to carry the abnormal gene. Sickle cell anemia is an example of a recessive mutation with a strong ethnic association and little genetic heterogeneity or new mutation. Cystic fibrosis also has a strong ethnic association and a low frequency of new mutation but greater heterogeneity. Fragile X affects all ethnic groups and often appears sporadic, but all cases have the same type of mutation, and a premutation can be found in all affected families. In the near future, the extreme sensitivity of DNA analysis will allow testing for these and similar diseases to be performed in vitro on fertilized embryos before implantation.