Out of dnaL: mapping the medical maze.

An estimated 250 million people, or 4.5 per cent of the world population, carry a potentially pathological haemoglobinopathy gene.

Every year, 300,000 infants are born with major haemoglobin disorders, the most common being the thalassaemia and sickle-cell disorder.

Prevalence varies from under 0.1 births per 1,000 in some parts of the worm to more than 20 per 1,000 in parts of Africa.

Worldwide, about 5 per cent of children are born with a congenital or hereditary disorder and almost 40 per cent of adults are genetically predisposed to common diseases during their lifetime.

In developed countries, even under the best of conditions, congenital and genetic disorders account for a quarter of deaths under the age of one and 23 per cent between one and four.

Until recently, coronary heart disease was thought to be due to lifestyle alone. Factors such as smoking, diet and exercise play a major part, but a family history will often uncover genetic susceptibility. For example, a heart attack before the age of 55 years in a relative presents a significant risk.

Evidence started to accumulate about 25 years ago that risk factors such as high cholesterol levels and high blood pressure are genetically influenced. Recent research has uncovered "candidate" genes for other risk factors.

An estimated 3 million infants annually are born with major congenital malformations and most die by three. But, if all goes well, all human genes would have been mapped and identified by 2020.

The last 20 years have seen an explosion of knowledge about the role genes play in health, from the moment of conception to the day people die. DNA determines not only the congenital malformations that kill millions of children, but also predisposes people to mental illness and major noncommunicable diseases (NCDs) such as cancer, cardiovascular disease, hypertension, asthma, diabetes and rheumatoid arthritis. Single-gene defects, genetic predisposition and congenital malformations together form a large group of genetically determined conditions. Single-gene defects, such as cystic fibrosis, haemoglobin disorders and haemophilia, are an important cause of fatal or chronically disabling diseases, especially in childhood. More than 9,000 single-gene conditions have now been identified. They occur worldwide, although some are more common in certain ethnic groups or geographic areas. Their incidence may be affected by differing demographic and cultural factors, such as maternal age or the prevalence of cousin marriages, for example.

Haemoglobin disorders-conditions that involve errors in the production of oxygen-carrying haemoglobin in the blood - are a striking example of the magnitude of single-gene defects. Genetic predisposition is determined by the individual's genetic make-up which contributes to susceptibility or resistance to disease. The picture is made further complex, involving an interaction of environmental factors. Diseases linked to genetic predisposition are equally devastating. Not only do they kill prematurely, but result in long years of ill health and disability, loss of work and income, possible poverty, loneliness and depression.

The burden of genetic disorders also falls on the health services of every country. Already today, diabetes mellitus, which affects at least 140 million people worldwide, with many of these cases genetically predisposed, alone accounts on average for 8 per cent of total health budgets in industrialized countries. By 2025, the World Health Organization (WHO) projects a more than twofold increase - up to 300 million - in the number of people with diabetes worldwide.

Human genetics has enormous potential to achieve better health for all and halt the advance of NCDs. It can provide us with the ability to give more accurate lifestyle advice, to screen, diagnose and counsel. Genetics has now advanced to the point where there are genetic tests for a number of conditions. In many cases, these can be carried out prenatally. Among the new techniques will be gene therapy - the introduction of a gene sequence into a cell with the aim of modifying the cell's behaviour - perhaps to correct a genetic mutation (as in cystic fibrosis), to destroy a cell (as for cancer) or to modify susceptibility (as for coronary artery disease). Early trials of gene therapy are already underway.

Cystic fibrosis (CF) used to cause the death of affected children before the age of two. Earlier diagnosis and special treatment have improved its prognosis so much that life expectancy is now around 30. Since the CF gene was identified in 1989, there has been unprecedented progress leading to improved drags and trials of gene therapy. Such treatments should be available within the lifetime of most current patients, improving the outlook even further. But controversies rage over issues such as the ethics of patenting genes or whether cloning should ever be permitted. Human dignity and well-being remain at the centre of the many basic ethical, legal and social issues involved in the development of human genetics.

The medical community is debating what could be done to avoid having people who undergo genetic tests equate a "defective gene", or a "genetic mutation" with a death sentence for them and their families. There is insistence that the results of genetic tests should be confidential for fear of a "genetic underclass". Scientific, medical and lay communities should ensure that genetic information and technology are used to preserve the dignity of the individual. The availability of diagnostic techniques for genetic disorders that cannot be either treated or prevented also raises ethical issues, which should be discussed with the communities, patient interest groups, the medical profession and organizations involved in counselling.