Introduction

  As we enter the era of molecular medicine, the impact of basic biological research on clinical practice has arguably never been greater. Physicians have already gained routine access to a new and powerful set of tools for the diagnosis, prognosis and treatment of common diseases as well as hereditary disorders. Molecular concepts and techniques permeate the medical literature, as advances in genetic manipulation are applied to clinical problems. The principles of molecular biology are taught as an integral component of the medical school curriculum. The pharmaceutical industry already offers the physician a variety of powerful reagents based on recombinant DNA technology, with new discoveries of clinically useful therapeutic proteins reported weekly. A handbook of the human genome will soon be available through the massive DNA sequencing projects that have been launched internationally, providing the medical community with an unprecedented opportunity to identify the genetic loci involved in human pathologies.

  To cite a few examples, the genetic lesions underlying familial hypertrophic cardiomyopathies were unknown ten years ago, but today physicians appreciate the molecular basis of this disease as well as other inherited cardiac abnormalities, and are approaching an understanding of the molecular mechanisms that predispose patients to cardiac malfunction (you will hear more about this subject from Dr. Seidman). Genetic testing is available for prenatal diagnosis of many congenital defects (Dr. Holmes9 clinic will cover this topic in detail). Recombinant human proteins for clinical use are increasingly available: diabetics now have access to purified human insulin, and human growth hormone counteracts stunted growth in children. The routine administration of human tissue plasminogen activator and other recombinant thrombolytic agents is a major step forward in the treatment of myocardial infarction. Finally, new animal models of genetic disease, generated with sophisticated transgenic and gene knockout technologies, hold great promise for the development of new therapeutic protocols for human application (we will discuss this in more detail in the Animal Models lecture). In short, our understanding of the molecular basis of human disease is in an exciting phase of growth that is likely to revolutionize the practice of clinical medicine in the years to come.

  These lectures cover the basic concepts and techniques of molecular biology as they apply to the material presented in this course. Designed as a brief review and reference source, they are by no means exhaustive but serves primarily to prepare you for the specific applications of molecular genetics in the succeeding lectures and clinics. Further reference material is provided at the end for more in-depth coverage of each subject.