A fragment of the DNA molecule, the chemical blueprint of life which is found in almost every cell of the body. Genes carry instructions for the production of proteins that determine the physical characteristics of an individual. They are passed on from one generation to the next, and are the basic unit of inheritance. Mutations in genes can cause inherited disorders.
HUNTING the gene for a human disease is like navigating the globe during the Middle Ages; there is a lot of uncharted territory and what maps exist are inaccurate and incomplete. The situation, says one gene hunter, is akin to searching for a burnt-out light bulb in a house with no address in an unknown street in an anonymous city in a foreign country.
Despite the difficulties, the gene hunters are gradually and methodically drawing up a map of the genetic blueprint that maketh man and woman. They are finding a new gene responsible for one of the 4,000 or so single-gene diseases, such as cystic fibrosis, at the rate of almost one a week. Eventually, the gene hunters hope to produce a genetic atlas of humankind, with the position of each of the estimated 100,000 genes assigned a position along one of the 46 human chromosomes.
Mapping the entire genetic blueprint - the human genome - and finding genes for the thousands of inherited disorders afflicting the lives of millions, will revolutionise medicine. It raises the possibility of doctors one day being able to create a genetic read-out of their patients; a breakdown of inherited traits that could cause ill-health in later life. It will give people some idea of what they may die of and when, or what disease they will be susceptible to and how they can avoid it.
Discovering the genes for inherited disorders will enable doctors to transform medicine, by replacing defective genes with healthy substitutes in a new form of treatment known as gene therapy. Gene mapping will give doctors the tools for widespread screening of the population for inherited traits, from single-gene diseases to disorders resulting from a number of genes influencing each other, such as heart disease and high blood pressure. It will also open a Pandora's box of ethical and social problems. Should life insurance companies also have access to genetic information to assess a person's risk of ill-health? Should diagnostic tests be made available for crippling disorders that have no cure? Who is to judge what are the 'bad' genes? And what pressures will science come under to identify 'good' genes that influence beneficial personal traits, from height to intellectual giftedness?
The current revolution in medical genetics has its roots in the 1950s when two Cambridge scientists, James Watson and Francis Crick, unravelled the double-helix structure of deoxyribonucleic acid - DNA - the chemical blueprint of life. Discovering the structure of DNA quickly led to an understanding of how the molecule stores genetic information, and how this information is used to orchestrate the activities of each cell in our body.
But it is only in the past decade or so that scientists have perfected the techniques of cutting and manipulating DNA in such a way that they can identify human genes individually and grow or 'clone' them inside microbes in the laboratory. They can insert these genes into foreign cells, whether animal or human, and in so doing bypass Nature's own way of mixing genes and DNA.
The facts about DNA give an idea of its importance. It is packed tightly into each of the 46 chromosomes found in each of the 100 million million cells of the body. It is a gigantic molecule. If all the DNA could be pulled out of the 46 chromosomes of one cell and stretched end to end it would measure about 2 metres; yet it is so thin that it is barely visible even with the most powerful microscope. If all the DNA in a human body were stretched end to end it would be long enough to reach the Moon and back about 8,000 times.
The reason why the DNA molecule is so long is not entirely clear. It seems that only a small proportion of it, perhaps less than 10
per cent, carries genetic information in the form of genes, the individual units of heredity. The rest has been called 'junk DNA', an unfortunate name given that it is likely to have some important structural or controlling functions. It is, however, the information-rich 10 per cent - the genes - that has aroused the interest of scientists.
So how do scientists locate individual genes? They look for some other inherited characteristic that is strongly associated with the gene in question. In his book The New Genetics and Clinical Practice, Sir David Weatherall, professor of clinical medicine at Oxford University, says the idea is beautifully simple. Because genes are constantly being shuffled from one generation to the next, if two genetic traits are frequently inherited together, they are likely to be physically close to each other on the DNA molecule. 'If the two are so closely linked that they will always pass together through successive generations, we now have a 'handle' on the gene that we can't identify; if the marker gene is inherited so must our gene that is closely linked to it be. And, if we know the chromosomal location of our marker gene, then it follows that the gene that we cannot identify must be close to it on the same region of that particular chromosome.'
Locating genes responsible for disorders that affect predominantly one of the two sexes, such as colour blindness and haemophilia, has been relatively easy using this approach. The gene can be assigned to either of the two sex- determining chromosomes, X or Y. But it is only since about 1980 that the revolutionary techniques of genetic engineering - the cutting and splicing of DNA - have enabled the gene search to really take off. In 1973, for instance, just 25 genes had been located. By 1989 the figure had grown to 1,656. In the following two years, a further 836 were added to the list. What has helped to revolutionise the search is the discovery in the past decade or so that much of the so-called junk DNA can be used to pinpoint genes. Scientists have discovered that this part of the DNA molecule has useful 'landmarks' - where component parts of the DNA appear in a recognisable order - which can be used to gauge distances between genes and to establish where they are. Much of the map-making activity in genetics is concerned with identifying these landmarks, which can then be used to discover genes.
Making genetic maps, like geographical cartography, is more easily done in cooperation with other map-makers. Which is why, in the mid 1980s, scientists decided to set up the Human Genome Project, to bring together the work of hundreds of research groups around the world. The aim is to map and identify all human genes and to decode the genetic message along the complete length of human DNA, even the 'junk', which may prove nevertheless to contain some useful information. Biologists equate the task with the goal set in 1961 by John F Kennedy: sending a man to the Moon. Although the cost will be far less, James Watson, a leading proponent of the project, believes the implications are likely to be far greater: 'A more important set of instruction books will never be found by human beings,' he says. 'When finally interpreted, the genetic messages encoded within our DNA molecules will provide the ultimate answers to the chemical underpinnings of human existence.'
Already, the 'new genetics' has shown it is possible to perform feats scientists felt were impossible only a decade ago. For instance, the gene for cystic fibrosis - the most common inherited disorder of Caucasians - was found in 1989. Until then, doctors had little idea of the root cause of the disease, but identification of the gene led to an understanding of the mechanism that goes awry in children suffering from it. Scientists could thus work back and find out more about the disease - genetics in reverse. It was, Professor Weatherall says, 'the final vindication of the new genetics'.Reuse content