Basic genetics for the clinical neurologist

To the casual observer, the clinical neurologist and molecular geneticist would appear very different species. On closer inspection, however, they actually have a number of similarities: they both use a rather impenetrable language littered with abbreviations, publish profusely without seeming to alter the course of clinical medicine, and make up a small clique regarded as rather esoteric by their peers. In reality, they are both relatively simple creatures who rely on basic sets of rules to work in their specialities. Indeed they have had a productive symbiotic relationship in recent years and the application of molecular biological techniques to clinical neuroscience has had a profound impact on the understanding of the pathophysiology of many neurological diseases. One reason for this is that around one third of recognisable mendelian disease traits demonstrate phenotypic expression in the nervous system. The purpose of this article is to demystify the basic rules of molecular biology, and allow the clinical neurologist to gain a better understanding of the techniques which have led to the isolation (cloning) of neurological disease genes and the potential uses of this knowledge. Deoxyribonucleic acid (DNA) is the macromolecule that stores the blueprint for all the proteins of the body. It is responsible for development and physical appearance, and controls every biological process in the body. DNA is the hereditary material of all organisms with the exception of some viruses which use ribonucleic acid (RNA) and prions, that apparently only contain protein. However, its simple composition meant its great importance in biology was overlooked for many years. It was not until 1952 that Alfred Hershey and Martha Chase, and their experiments on bacteriophage, finally proved that DNA and not the more complex protein was the hereditary material. DNA is made of two anti-parallel helical polynucleotide chains wrapped around each other and …