The impact of DNA analysis on fetal diagnosis

There has been rapid progress in mapping disease-specific gene loci to particular chromosomal regions and in cloning the relevant genes or DNA sequences that can act as genetic markers. These advances will have an impact on fetal diagnosis of monogenic disorders for a number of reasons, the most important being the ability to use chorionic villus DNA taken in the first trimester to make a fetal diagnosis, no matter how tissue-specific the gene defect. Diagnosis based on analysis of the protein gene product requires a tissue that is expressing that gene. In a few disorders the mutation within the gene can be detected directly, but more often an approach, termed gene tracking, will be required to predict the genotype of the fetus. This requires blood samples from a few family members and the analysis must be carried out prior to the chorion sampling and ideally before the pregnancy. This initial family study is required to determine whether gene tracking is possible in that particular family. A number of potential problems, both technical and in clinical management, highlight the need for close collaboration between clinical geneticists, molecular geneticists and obstetricians.