Prenatal diagnosis: current status and future trends

Many of the major single-gene disorders in man can now be detected in utero using restriction fragment length polymorphisms (RFLPs). This approach is based on the knowledge of established linkage between RFLPs and mutations in an adjacent gene. The development of the polymerase chain reaction has altered the available approaches to this problem. This technique permits very rapid detection of the specific mutation from small amounts of starting material and may enable us to detect the genotype from fetal cells in maternal blood or from single cells in embryos before implantation. This may lead to the selection of embryos that lack a defect before they are implanted, avoiding the need for termination of pregnancy. Perhaps the greatest ethical challenge related to the application of these techniques will come with the understanding of the genetic basis for common polygenic disorders. The clarification of the multiple genetic factors responsible for a large part of susceptibility to diseases such as diabetes mellitus, rheumatoid arthritis or ischaemic heart disease will be greatly facilitated by a one-centimorgan genetic map. The strategy involved in establishing such a map, using the polymerase chain reaction, and then the identification of genetic loci responsible for susceptibility to a typical polygenic disease (insulin-dependent diabetes mellitus), is discussed. The ability to identify individuals at high risk of developing such diseases may present opportunities for early intervention.