Molecular diagnostics: between chips and customized medicine

Recently there has been an explosive increase in molecular diagnostics. This is due to translational research on the molecular basis of human diseases, and to technological developments that have resulted in efficient procedures for extensive analysis of the human genome. However, a large body of data on the genome is still difficult to interpret at the clinical level. For many monogenic diseases, "modifier'' genes, inherited independently of the disease gene interact, thereby resulting in a distinct phenotype for each patient. Multigenic diseases depend on complex interactions between genes and the environment. Response to drugs and side effects are modulated by gene variants. The same is true for the response to nutrients. All these interactions, which vary from patient to patient, led to the concept of "personalized medicine''. Our genome consists of 25,000 genes, a surprisingly low number when compared to other species. Therefore, the complex phenotype of humans depends on a number of mechanisms that regulate gene expression, which, in turn, may be altered resulting in disease. For example, DNA methylation modulates the level of gene expression, and altered methylation of some genes is related to human neoplasias. MicroRNAs regulate the expression of a myriad of genes, and mounting evidence indicates that this mechanism may be impaired in human diseases. Finally, the relationships between genetics and human behavior are starting to be elucidated. For example, suicide may be related to alterations of methylation of specific genes. To conclude: the chip-wide analysis of human genomes is becoming easier, but the understanding of molecular genetics that confirmed the real "uniqueness'' of each genome is an excellent opportunity for laboratory medicine to reposition the patient at the heart of the medical process. Clin Chem Lab Med 2010; 48: 973-82.