GENETIC ENGINEERING: Redrawing the Blueprint of Life - 2. Inheriting Disease

child with cystic fibrosis

Figure 1. A three-year-old child with cystic fibrosis receives treatment from a physiotherapist. Rubbing and clapping on the back and chest loosens the mucus, which is coughed up.

two ways to inherit a genetic disease

Figure 2. Two ways to inherit a genetic disease.

how a person's sex is determined

Figure 3. How a person's sex is determined
Note: egg and sperm not shown to scale.


Figure 4. An amniocentesis test being carried out in early pregnancy.

in vitro fertilization

Figure 5. In vitro fertilization. At the IVF unit in a London hospital, a technician looks through a microscope at egg cells and sperm in a dish to check for successful fertilization.

In the United States alone, 30,000 young people suffer from a serious disease called CYSTIC FIBROSIS (CF). Children with this condition produce a thick, sticky mucus that can clog the air passages of their lungs. The build-up of mucus also makes it easier for harmful bacteria to multiply and cause life-threatening infections (see Figure 1).


At present, the treatments available for CF do not make the disease go away. But by simply helping to break up the mucus or by killing some of the germs that breed in it, the treatments reduce the chances of infection. A person suffering from the disease must have regular physiotherapy. This involves being rubbed on the chest and clapped on the back so that the mucus is loosened and can be coughed up. A variety of medications can also be given to help control the amount of mucus and limit the spread of bacteria. Even so, few people affected with this condition live much beyond age 30.


Cystic fibrosis is a genetic disease. It is passed on to a child trough the genes of its parents. Until recently, no one knew which gene or genes among the many thousands contained in a person's DNA were responsible for the disease. But in June 1989 a team of Canadian and American scientists found the single gene that is responsible for CF. Now, it is hoped, this breakthrough will lead to the possibility of earlier diagnosis and more effective forms of treatment.


Genes from our Parents

To understand how genetic diseases come about, remember that all genes (except those in egg and sperm cells) occur in pairs. One member of each pair comes from the mother and one from the father (see Figure 2).


Nearly all individuals have a few disease-causing genes among their DNA. For example, among Caucasians (white-skinned people), about 1 person in 20 is thought to carry the gene responsible for cystic fibrosis. But normally this does not matter. Because the disease-causing gene is almost always recessive, its instructions are rarely used. Instead, its dominant twin, which in most cases is healthy is the one that is "switched on."


Inherited diseases are of two types. The first are those resulting from a disease-causing dominant gene inherited from either the father or the mother. In this case, the parent who passes on the unhealthy gene must also be a sufferer of the disease.


The second type of genetic disease comes about when a child receives the same disease-causing recessive gene from both parents. Since there is now no choice but for one of the unhealthy genes to be switched on, the child will suffer from the disease. Cystic fibrosis is caused in this way.


Troubles with X

Just one special chromosome makes the difference between whether you are a boy or a girl (see Figure 3). If you are a girl, the chromosomes from each of your body cells could be sorted into 23 matching pairs. But if you are a boy, your body cells contain only 22 matching pairs. In the other pair, the chromosomes don't look alike – one is shaped like an X, the other is smaller and shaped like a Y.


All of a woman's egg cells contain X chromosomes. However, half a man's sperm cells have an unpaired X and the other half an unpaired Y. Your sex was determined by whether the egg from which you grew was fertilized by a sperm containing an X chromosome or by a sperm containing a Y chromosome.


Some genetic diseases, said to be SEX-LINKED, are caused by unhealthy genes on the X-chromosome (never, so far as we know, on the Y). One of these sex-linked diseases is HEMOPHILIA. A sufferer from this disease has blood that does not clot properly. As a result, even small cuts and bruises, if left untreated, can lead to serious bleeding.


Because hemophilia is caused by a recessive gene on the X chromosome, a woman who has the hemophilia gene on just one of her X chromosomes in her normal body cells will not show any signs of the disorder. She will, however, be a CARRIER. This means that she can pass on the disease-causing gene to her offspring. Any male child who inherits the hemophilia gene on his mother's X chromosome will have the disease. As a result, there is a high risk (1 in 2) of a boy having hemophilia if his mother is a carrier. A girl's chance of inheriting the disease is very low. For a girl to be a sufferer, both the X chromosomes she received from her mother and the X chromosome she received from her father would have to contain the gene responsible for hemophilia.


People who have a family history of inherited disease can be given advice on how likely they are to pass on a genetic disorder to their children. This advice is called GENETIC COUNSELING.


To see if a person actually has any disease-causing genes, doctors can carry out a variety of tests. Such tests are known collectively as GENETIC SCREENING.


Testing Before Birth

A developed but unborn child, or FETUS, can undergo prenatal (before-birth) screening to give some idea of the chance that it will inherit a genetic disease from its parents. Such screening cannot, however, give information on whether a disease will show itself early or late in life, or whether the child will be mildly or severely disabled.


One of the tests carried out before birth, known as AMNIOCENTESIS, is done 14 to 15 weeks after the mother becomes pregnant (see Figure 4). An ultrasound scanner, which gives off very high-pitched sound waves, is used to form a moving TV picture of the fluid-filled bag (the amnion) that surrounds the fetus. The doctor then draws off a small sample of the fluid with a hypodermic needle. Inside the sample will be a few cells from the fetus. DNA from these cells can be examined to see if it contains any disease-causing genes.


A more recently developed method of obtaining cells from a fetus is called CVS (chorion villus sampling). This test allows doctors to detect serious genetic diseases in a fetus that is only 8 to 10 weeks old. Guided by an ultrasound scanner, doctors take some of the cells from the place (the chorion) where the young fetus is joined to the mother's body. The extracted substance gives enough DNA from the fetus for results to be obtained in a day or two. In contrast, the older technique of amniocentesis provides only a few cells, which are then allowed to reproduce themselves in the laboratory until they form a big enough sample. This process can delay the outcome of the test by several weeks.


One of the advantages of prenatal genetic screening is that it offers a family a chance to prepare for the special needs of a child who may have a genetic disease. Such preparation might include talking to other parents of children with the same disorder and joining a support group.


A Matter of Life and Death

Prenatal screening also raises a very controversial issue. On learning that her unborn baby may develop a genetic disease, an expectant mother might decide to have an abortion. There is great disagreement in the United States and in other countries about whether abortions should be carried out under any circumstances. And there is a particular debate about whether abortions should be performed to prevent the births of children with physical or mental disabilities caused by genetic disease.


Eventually, this problem is likely to be made more complicated because of a technique called in vitro fertilization (IVF). IVF allows egg cells from a woman and sperm cells from a man to be brought together in the laboratory see Figure 5). Usually a number of fertilized cells develop in the laboratory, and one is chosen by the doctor to be placed inside the mother to develop into a baby. (The technique has given rise to the expression "test-tube babies").


In the future, it will be possible to screen each of the fertilized eggs for disease-carrying genes. When a fertilized egg without any disease-causing genes is found, the doctor will be able to implant this in the mother. It remains for society to decide whether such a selection should be legal and how far choosing the genetic characteristics of children, in general, should be allowed.


Tracking Down the Causes of Genetic Disease
Researcher is working under an ultraviolet light while preparing a gel used in the separation of DNA. The visor is worn to shield the eyes from the UV light.
A researcher working under an ultraviolet light while preparing a gel used in the separation of DNA. The visor is worn to shield the eyes from the UV light.

How do researchers pinpoint which gene is responsible for a particular disease? The task may seem like looking for a needle in a haystack, when you consider that our 46 chromosomes contain around 100,000 genes, any one of which might be the culprit. In the case of some disorders, the search is made easier because the chromosomes on which a particular gene lies may be partly absent in sufferers of the disease. Such missing bits of DNA help to narrow down the area of the chromosome that must carry the crucial gene in healthy individuals. In the case of other genetic disorders, all the chromosomes appear complete. Researchers then have to study samples of DNA taken from many individuals – parents, children, grandparents, cousins – from families in which a particular disease tends to occur. This technique allows sections of DNA called "markers" to be identified. Markers lie on either side of the disease-causing gene. The closer a marker is to the required gene, the more likely it is that both the marker and the gene will be passed down from generation to generation. Through careful analysis, over a number of years, scientists have used this method to track down the specific genes responsible for diseases such as cystic fibrosis.