Chapter 28 – Molecular Diagnosis of Human Disease

Publisher Summary Developments in molecular diagnostics primarily reflect technological breakthroughs that originated in molecular biology, from the description of the Southern blot to the clinical applications of the Polymerase Chain Reaction (PCR) and high throughput sequencing. Specific medical utilization of these molecular biology tools coincided with basic scientific breakthroughs. Superimposed on these areas came changes in the regulatory environment, originated by existing regulatory agencies, professional organizations, and new advisory committees, all of whom strived to describe the good laboratory practices that all clinical laboratories should attempt to attain. This chapter describes these laboratory and regulatory aspects and the most likely areas for future applications, along with the possible factors that may restrain growth and development. It provides a brief background into the history of molecular diagnostics and describes the impact of regulatory agencies, professional organizations, and ad hoc committees on the analytical and clinical applications, particularly of molecular tests for heritable conditions. It also presents some examples of molecular testing in infectious diseases, oncology, drug metabolism (or pharmacogenetics), in addition to heritable disorders and illustrates, for each category, the pre-analytical, analytical, and post-analytical considerations that comprise good laboratory practice. It then provides the specific examples to understand new concepts or mechanisms regarding disease pathogenesis and/or treatment and particularly reviews these unique applications: (i) clinical diagnosis, (ii) population screening, (iii) selected screening, and (iv) tests associated with disease prediction and risk assessment. The chapter further focuses on future growth areas, including multivariate analyses, personalized medicine, automation, and miniaturization, while acknowledging constraints, such as reimbursement and regulatory stagnation.