genetic testing

genetic testing is now possible, as both the structure of DNA is known and methods to determine the sequence have been developed. Genetic testing brings with it benefits of diagnosis and treatment, but raises many other issues, both sociological and ethical. It is known that a great number of diseases have a genetic input; in some instances, such as single gene diseases, the genetic mutation is the sole cause of the disease. In polygenic diseases there are a number of mutations in different genes, none of which individually may have any measurable effect, but which in combination one with another may increase the likelihood that a complex disease condition, such as high blood pressure, will result.

What is genetic testing, what does it involve, and how is it done? We all have 22 pairs of chromosomes, one of each pair from each parent plus an X and Y chromosome in the male and two X chromosomes in the female. Paired genes are arrayed along the length of each pair of chromosome. Thus we all have two copies of each gene, one from each parent, plus either an X and a Y or two X chromosomes. Suppose the particular gene on a particular chromosome carries a defect responsible for a disease, while the other gene on the paired chromosome is normal, yet the person has the disease. Then the mutant gene is said to be dominant. If no disease is present then the gene is recessive; the person is a carrier, but may pass on the defective gene to the offspring. It is important to know in genetic testing whether an individual has two normal genes or one normal and one abnormal gene. Some genetic diseases are associated with X and Y chromosomes and are described as sex-linked, while genetic diseases due to gene defects on the non-sex chromosomes are called autosomal; i.e. these can affect males and females alike. Genetic testing therefore consists of looking for the gene mutation, together with the normal gene in a DNA sample, from a patient. Providing a sample is very easy; for example, simply lightly brushing the inside of the mouth yields enough cells to examine the DNA. Techniques are available to amplify (copy) the DNA in the sample, and, since the sequence of the gene involved is known, probes are used to look for the presence of normal and mutant genes. If only one type of gene is found then the sample is from a homozygous individual, who may have two normal or two abnormal genes. If both types of gene are found then the individual is heterozygous, that is they have one normal and one abnormal gene. Given this information, the consequences for the offspring follow clearly defined genetic rules. Examples of dominant inherited disorders are Huntington's chorea and retinoblastoma; of recessive disorders are cystic fibrosis (CF), sickle cell anaemia, and thalassaemia; and of sex-linked inherited disorders are haemophilia and muscular dystrophy.

Consider an example. A perfectly healthy pregnant female is offered a genetic test and discovers that she is a carrier of CF. It is most important that confidentiality is maintained and that the patient is not made to feel somehow responsible. If the father is also a carrier then the chances are 1 in 4 that the child will have CF. The chances that the child will also be a carrier, like the parents, is 50%, and the chance that the child inherits a normal gene from both parents is again 1 in 4. Testing the father involves some delay and, of course, concern for the parents. In some instances the father will be unknown or parentage of the child may be in doubt, raising further embarrassments for those involved. If the father cannot be found or refuses to take part it is possible to test the fetus by amniocentesis. In this procedure a small volume of fluid is drawn from around the foetus. This contains sufficient fetal cells to collect the DNA. If, when all the tests are done, the unborn child is found to have CF, then termination may be offered, again an ethical problem which the originally unsuspecting parents had never envisaged. Counselling is very important at this stage.

Looking to the future, it is possible that babies will be genotyped at birth and that this may allow prediction of diseases that might arise in later life. In this way prophylactic measures taken early may be able to prevent the disease appearing, or delay its onset. Furthermore, if the disease does develop, knowledge of the genetic profile will allow the most appropriate drug regimens to be prescribed. This sort of benefit will be most useful for polygenic diseases, such as high blood pressure, various forms of cancer, and asthma. It must be remembered, however, that complex diseases of this type have causes that are due both to nature and nurture. Clearly, much disease prevention can be achieved by appropriate attention to nurture — lifestyle, diet, and the like.

Alan W. Cuthbert