Molecular Diagnostics

Our understanding of the function of human DNA, known as the human genome, is steadily progressing. Cytogenetic methods have been in clinical use since the 1960s, and molecular tests for almost 2,500 rare monogenic disorders since the 1980s. Recently, genetic testing has also become an important tool in studies of familial cancer predisposition, where the numbers of those benefiting from testing are large compared with tests for rare diseases. In the near future, genetic testing may have an increasing role in determining risks for other common genetic diseases—such as cardiovascular diseases and common multifactorial diseases—and in pharmacogenetics. Genetic testing/screening makes use of a variety of technologies to identify inherited or acquired modifications in the genetic information of an individual. The technologies used can be cytogenetic, as well as biochemical and immunochemical, to verify the composition of DNA, RNA, proteins, carbohydrates and lipids. The result of this testing can yield different types of information, such as: (1) confirmation or exclusion of the diagnosis of a specific disease; (2) the magnitude of the risk, or its absence, of developing a disease or reacting adversely to drugs and environmental factors; (3) the magnitude of the risk of biological descendants inheriting a defect. The tests can be performed on individuals, or on nuclear or extended families. The term ‘screening’ is usually reserved for the systematic testing of the members of defined populations or high-risk population subgroups for one or more inherited modifications of the genome. As the technology improves and its cost decreases, the genome of individuals may also be screened for a series of related or unrelated inherited variants. Since the composition of the chromosomes and the DNA of an individual are fixed at fertilisation, most tests can be done at any stage of life, either before or after birth (pre-implantation diagnosis, all forms of prenatal diagnosis and neonatal and adult testing). In most genetics centres, the testing of children will be strictly limited to those cases in which a diagnosis is important for management or therapy. As a result, the possibilities for testing and screening for the genes involved in inherited diseases or susceptibility to diseases have increased spectacularly. In addition, modulators of gene expression — other genes, non-coding DNA sequences, proteins involved in the three-dimensional organisation of DNA and acquired (epigenetic) modifications of DNA — are being identified. This has led to the surprising realisation that even environmental factors, such as food components, might modify DNA function fairly dramatically. This means that most simple tests, as done today, will have to be complemented with tests allowing more precise predictions of the risks, of the progression and of the clinical characteristics of diseases. High-throughput DNA sequencing has also opened up a series of new approaches to the identification of individual characteristics, which may be relevant for determining the risks of developing diseases or of showing variation in the rate at which we metabolise drugs. Indeed, our DNA contains some distinct individual variation in its composition. Testing for predispositions to particular diseases and pharmacogenetic testing have potential for the future, although much research will still be needed before these approaches can be routinely implemented in practice. For example, despite the recent rush of offers from commercial companies, the comprehensive E1000 genome sequence is not an immediate prospect. Analysis of individual variants also allows the identification of biological traces collected at crime scenes with great accuracy. Application of this knowledge in forensic cases and in studies of biological descent has become routine. It is clear that we are only at the beginning of our understanding of the function of all the DNA fragments, but there are already many examples of how DNA analysis can contribute in medicine and in many other fields. This second edition of the book Molecular Diagnostics provides an excellent overview of the techniques that are available today for molecular research and diagnosis of inherited or acquired diseases. With an impressive BOOK REVIEW