Health: What your genes say about you

Tests for inherited disorders pose ethical dilemmas.

THE ERA of genetic testing is upon us, and one of the first uses to which it has been put is in prenatal diagnosis, to offer a woman the opportunity to terminate a pregnancy if she is carrying a foetus with a serious and incurable disease.

But few people really understand what genetic tests can do and, more important, what they cannot do.

Part of the difficulty is due to the complex nature of biological inheritance and how it impinges on the health of the body. About 80,000 human genes make up the human "genome". Each person inherits two copies of a gene, one from each parent (except for those on the X and Y sex chromosomes). Each copy can be identical or can differ slightly but still function correctly - although they may produce different physical effects, such as eye colour.

Some copies can be so different from the "normal" forms that they do not function at all. Most genetic tests are based on being able to detect the presence of mutations that make these genes defective.

But having a single, defective copy of a gene does not automatically result in the development of a genetic disorder. There are fundamentally three types of single-gene disorders. The first is when a single defective copy of a gene results in disease - a "dominant" disorder. In the second, both copies have to be defective to cause harm - a "recessive" disorder. The third is when the gene in question occurs on the X chromosome. These "sex-linked" disorders usually affect only males, but females can be healthy carriers. Haemophilia is a good example.

Scientists have discovered well over 4,000 inherited diseases caused by defects in single genes. Tests have been developed or are in the process of being developed to detect defective genes in blood, saliva or indeed virtually any body tissue, including hair.

A positive result does not always mean that a person will develop the disease. About 10 per cent of women who are positive for the breast cancer mutation on the gene BRCA1, for instance, never develop tumours. Similarly, a negative result does not mean a person will be for ever free of that disease. It may be that they carry, or develop, mutations in another part of the same gene that is not picked up by the test.

Another difficulty is that although genetic testing can tell whether a person is at risk of a particular disorder, it is a sad fact that practically all genetic disorders are incurable.

Genetic testing on adults raises other ethical concerns. Take, for instance, cystic fibrosis, the most common genetic disorder of white northern Europeans. It becomes increasingly crippling for sufferers during childhood; one of the biggest problems is a build-up of sticky mucus in the lungs, making breathing difficult.

Cystic fibrosis is a recessive condition, so a person can carry one defective copy of the gene in question without any ill-effects. But if he or she has a child with another carrier, there is a one-in-four chance that their baby will inherit both defective copies and so suffer from the disease.

A test for the defective copy of the "cystic fibrosis" gene was the first genetic diagnostic to be made directly available to the British public, bypassing doctors. This caused consternation among government experts, who recommended that these over-the-counter tests should be properly regulated and controlled.

The Advisory Committee on Genetic Testing saw a "limited role" for such tests, believing that they should be made available to assess a person's "carrier" status only for inherited, recessive disorders, and recommended that people should have direct access to a genetic test only if the result had no direct health implications for the person being tested.

The problem really begins with tests to determine a person's future health. Many genetic disorders occur in adult life. The best example is Huntington's chorea, which results in slow physical and mental decline. Huntington's is not only a late-onset disease, it is also dominant; if the test shows you have the mutation, it means that you are destined to die prematurely of a distressing, incurable illness.

The ethical dilemmas are exacerbated by the fact that a positive result impinges on other family members. If, say, a woman in her thirties decides to take the test because her father is dying of the disease, a positive result would also mean that her children are now at a calculable risk. They may prefer not to be burdened with knowing these odds.

As more genes are discovered, genetic tests will play an increasingly important role in determining risks of late-onset diseases. Some of these, such as Alzheimer's, heart disease and schizophrenia, may involve more than one gene, as well as environmental influences. Doctors of the future may be able to make good guesses about not just what patients are likely to die of, but when. It may help people to avoid a lifestyle that puts them at risk of premature death, but it will raise ethical concerns that we are only just beginning to comprehend.