Probably, applied genetics most impacts on society are as a result of genetic tests. In general, genetic tests seek to detect some feature of a persons genetic constitution. This feature can be a disease causing mutation or a marker DNA sequence used to detect presence of another gene. Obviously these procedures used for testing the status of DNA, RNA or chromosomes are included in genetic tests. What is more it is possible to include some protein based tests and classical medical examinations when they aim to detect inheritance of a trait.
Genetic tests have been divided into four categories in this text, and they will be examined in greater detail later. These categories are: Prenatal tests that are applied on fetuses during pregnancy. Neonatal screening just after birth and career screening of marrying couples. Testing for serious late-onset disease before the symptoms occur. Testing to assess the probability of developing complex disease. There are a couple of considerations about genetic tests: 1. First of all, the tests should be reliable.
When a positive or a negative result is obtained, we should be confident in that result with a confidence approaching 100%. To achieve such a high accuracy is not as easy as it may at first appear to be. Meiotic recombinations that always occur take place during gamete generation, may separate a disease-associated gene and a marker DNA sequence which is used to detect mutated genes. False positive or negative results could be obtained. In addition, genetic tests look for the most common mutations that cause the disease. For example, a test would detect CFTR?
F508 (Cystic Fibrosis Transmembrane Receptor) mutation, however it is not possible to detect infinite number of other mutations. Therefore, a genetic test can give such results so that the physician is convinced that his patient is normal while he is affected by an undetectable mutation. New tests are continuously being developed. Doctors and genetic counselors who will use these tests in the future, should be well informed about newly emerging tests. Extremely accurate genetic tests can only be developed by thorough experimentation on human subjects.
Although there is generally no physiological risk in experimenting a person, the subjects should be informed that the applied test is not entirely reliable and in experimentation state. Informing subjects of experimentation is an obligation set by the Nuremberg Code. Just after World War II it was discovered that unethical experiments had been performed on humans who were kept in concentration camps of Nazi Germany. This situation was discovered in Nuremberg Trials, and ethical and legal standards for medical experimentation were set then. Research and common medical procedures are distinct concepts.
If a genetic tests validity has been proven by extensive research and the test being used as a routine medical procedure to diagnose patients, it is no more considered as experimental and is not covered by the Nuremberg Code. Nevertheless, the patient should be well informed and his consent should be taken even before applying a routine test. The subject of the test should fully understand the nature of the test and the consequences that may arise from it. The subject of the test should be fully aware of the nature of the test and the consequences caused by the test.
Therefore, a professional counselor is needed to psychologically counsel and inform the subjects both before and after the test is taken. Sometimes, the person taking the test cannot give an informed consent when it is a small child or mentally retarded person. In this case, it is still required to take consent of the parents or legal guardians. The tests should only be applied for vital medical reasons. For example, it is not very ethical to test a young girl for a sex linked genetic disease. Because it is intensely related with the future life of the girl, her consent should be taken.
As a rule of thumb, the physician performing the tests should consider the childrens opinion and give an increasing importance to them with their age. Tests should not be carried out if there is not sufficient reason to do so. The person tested may face extremely unfavorable outcomes and this may cause psychological distress. Deciding to get married, becoming pregnant, taking some medical precautions before the first symptoms come about and taking financial and career decisions are examples of reasons that justify taking of a test.
The rights of knowing someones own health status and keeping that information private to oneself should be provided to all members of a society. Only the individual should have full access to information about his own genetic constitution and others should be prevented by legal regulations. As we have said above, the results of genetic tests can sometimes be detrimental to the individual. If a person does not want to know the information, its nobodys business nor right to declare it. This includes even not explaining favorable test results without the individuals request.
Influences of genetic tests can sometimes go far beyond the nuclear family. Especially in some illnesses penetrance shows extreme variability. So, strike of the disease may skip generations or at least some individuals. A distant relatives genetic status may as well bother an individual. He cannot take his parents being healthy as an evidence for his being healthy. Parents can be carriers without showing the symptoms. There can be contrasting situations where one wants to know his genetic status and another objects his taking the test refraining from unintentionally learning some unfavorable information.
Prenatal Testing Prenatal testing is the process of testing the genetic status of an embryo when there is a risk of a serious monogenic disease or when there is a proliferated risk of gross chromosomal disorder such as Downs syndrome. Prenatal testing should only be done if the parents are determined to terminate the pregnancy in the event of an unfavorable outcome. It is a very beneficial technology as it encourages couples, who had one genetically defective baby and do not want to have another child because of high risk, to attempt pregnancy by assuring them that in an adverse result pregnancy can be terminated.
Positive aspects of such tests are easily distinguishable. However, there also are a number of controversial points. Prenatal tests are not totally free of risk. During prenatal tests, a sample from the embryos cells should be taken out by a procedure known as amniocentesis. It involves insertion of an injection to mothers uterus and sucking some fluid from chorionic villus of the embryo. It can disturb the embryo. Amniocentesis carries a 1% risk of miscarriage. So, prenatal tests should only be applied when the risk of having a defective baby is much higher.
Prenatal tests should only be made with an idea of termination of the pregnancy in mind. Genetic counselors should explain what it means thoroughly to the couple. As it is explained above, prenatal tests carry a considerable risk of miscarriage and it is not sensible to perform them if the couple would carry on with the pregnancy whatever the result is. Nonetheless, parents always keep the right of not terminating even if they will have a defective child. Some ethnic and religious groups may object the application of prenatal tests because of not accepting in principle the procedures like abortion following test.
However, abortion is the legal right of pregnant woman in most countries and no one should be let to interfere with usage of this right. A lot of tests are applied to pregnant women to assure themselves and their embryos health status. It is a possibility that the prospective mother may not understand or confuse the nature of prenatal test. She may take a test without a view of termination. And she may become faced to carry out pregnancy in the knowledge that her child will be born defective i. e. with Downs syndrome.
Of course, prenatal tests should be routinely carried out when necessity arises, but the time should be taken to explain the nature of the test to the prospective mother. Neonatal Screening Neonatal screening is performed just after the babys birth to test for the presence of common genetic disorders such as Phenylketonurea, CF or genetic anemia. Neonatal screening is not carried out for very rare genetic diseases or when there is no possible treatment or precaution to be taken. However, some illnesses, which are widespread in certain ethnic groups, are routinely tested in developed countries.
For example, phenylketonurea is a genetic defect, which causes mental retardation of the child due to phenylalanine accumulation in the brain. The babies testing positive for this disease can grow with healthy minds if a phenylalanine diet is applied for the first few years of childs development. For all genetic tests, it would be nice to inform the parents about the nature of the test. However, there is usually not sufficient time, so the tests are applied routinely without asking the parents. The benefits obtained outweigh this adverse situation.
Carrier screening may be applied to decrease the incidence of a genetic disease within a community. Although the frequency of the defective gene will not change, at least homozygous recessive mutation carrying individuals are not produced. Carrier screening is applied when a couple decides to get married. If their offspring are in considerable risk, they may decide not to marry, not to have children or apply prenatal tests during pregnancy and abort any defective embryos.
Carrier screening for halassaemia in Cyprus and Sardinia has decreased the incidence of the disease. It is also carried out to test for the mutation that causes Tay-Sachs disease that is common in Ashkenazi Jews. In both cases the religious leader supports the programme and warns the couples both of which are carriers before they get married. Carrier screening may result with genetic discrimination against carriers. People who have been diagnosed as carriers may find it difficult to find partners for marriage, may be discriminated against by employers or insurance companies.
For example, carriers of sickle cell anemia who were identified as a result of a compulsory population-screening programme during 1970s, were discriminated against in several American states. Although the geneticist who performs the population screening for rational reasons knows that being a carrier does not reduce physical or mental activity, the society can sometimes irrationally stigmatize such individuals. In this case, discriminating against carriers is not only unjust and unethical but also ridiculous.
Presymptomatic Testing for Late Onset Diseases It is possible to test individuals for a late onsetting disease before the first symptoms are seen. Huntingtons disease, familial Alzheimer disease, familial Coulomb cancer, or familial breast cancer are all examples of late on setting genetic disease. No symptoms are seen until late adulthood. Testing for these late onsetting diseases is theoretically different from testing for predisposition to complex diseases. Because in all the diseases cited, either the onset of the disease is unavoidable or has a very high probability. However, some late onset diseases are not inevitable.
Even if the patient carries the disease defining mutations. For example, a woman carrying dominant mutation of BRCA-1 gene has a penetrance rate of 50% by age 50, and 85% throughout life. BRCA-1 mutation causes breast cancer, but developing it without BRCA-1 mutation is still a considerable risk for women. In Huntington s disease, although the occurrence of the symptoms is certain, age of onset can change between 50 and 60 years. Similarly, severity of symptoms is also influenced by various variables such as lifestyle or presence of other genes.
Testing for serious late onset diseases is very extraordinary, because the tested person is completely healthy at the time of the test but if the results come to be positive, he or she learns that in the future suffering from a devastating disorder is unavoidable or at least very likely. An undesired test result causes psychological distress not only on the person being tested but also on his or her family members. Children of the tested individual will feel guilty and sad for their parent and at the same time will be in the knowledge that the same mutation may be present in their genomes.
Moreover, as it will be explained later, insurance companies or employers may require the results of genetic tests and a later on discriminate against them. Since many negative changes may take place in the lives of the individuals taking the test, there should definitely be logical reasons for taking the tests. For instance, a person who has a close relative such as a father or a sibling suffering from familial colon cancer may take the test. If the test results come to be positive, he may have his colon removed and escape from being cancer.
Or a young woman, testing positive for BRCA-1 mutation, which causes breast cancer, may chose to have children at younger ages and then have her breasts removed to avoid the probability of a cancer For Huntingtons disease and Alzheimer, there is yet no possible treatment and it seems that none will be available in the next ten years. Despite this, taking a test might be advantageous for some individuals. They can make appropriate life choices like marrying, having children, financial and carrier choices if they knew for certain that they will develop the symptoms.
Presymptomatic Testing For Predisposition To Complex Disease Those diseases, which are caused by a combination of multiple genes and environmental factors, are named as complex diseases. Testing predisposition to complex diseases is more difficult because it requires testing many genes most of which are not yet identified. We know the contribution of a genetic factor without knowing any involved genes because its possible to calculate genetic contribution (inheritability) by studies on monozygotic and dizygotic twins.
Testing for complex disease predisposition is not common, because of the lack of sufficient kits. However, new technologies such as DNA microchips are being developed, which will enable testing of many genes at the same time and calculating the probability of a disease. In the future, probabilities of various complex diseases will be identified during neonatal screening, and the parents of the children will be advised what environmental risk factors to avoid to bring up their children to a healthier future. It is important to distinguish between serious late onset diseases and complex diseases.
Probability of developing the disease in the former one is much higher compared to the latter. Environmental factors may affect both of the cases, but for the former one only onset age and severity of the symptoms change and unfortunately preventing the start of the diseases is impossible. Finally, genetic discrimination may also be possible for complex diseases. Employers may refrain employing such people and insurance companies may want increased premiums to cover their health care costs.
Abortion There is probably no more controversial issue in society than the issue of abortion. Widely contrasting views are argued with equal eagerness among physicians, clergy, feminists, sociologists, and everyone else who is asked to express his ideas. Abortion is the legal right of the pregnant woman when there is a proof that the embryo or fetus will be genetically defective. However, all genetic defects are not so serious. For instance, although Downs syndrome causes mental retardation, there are people suffering from the disorder but still able to read and write. There is a spectrum of severity for many genetic illnesses.
And it is difficult to foresee the result of a pregnancy just by prenatal diagnosis tests. Some parents having a Downs syndrome stricken child, report enjoying an emotional and happy life. The situation for late onset disorders is even more complicated. Molecular medicine is progressing very fast and most of those illnesses will be cured in the near future. However, nobody can predict it with certainty. It is a hard decision for a mother to bear a baby with such illnesses. Laws and regulations about abortion show large variety in different parts of the world.
However, usually the parents have the right to abort a fetus which will be born with a severe genetic disorder. Development in molecular medicine make the treatment of many illnesses possible which were previously lethal. So, the parents will face a dilemma: Should they abort a child with a genetic defect or should they decide to bear it hoping new treatment strategies will be discovered in the future. F. Preimplantation Genetic Diagnosis It has been 10 years since the first preimplantation genetic diagnosis (PGD) babies were born.
During this time it is estimated that approximately 50 centers worldwide have begun offering PGD for a variety of disorders, including single gene defects, chromosomal imbalances and sexing for sex linked diseases. The first step in PGD process involves taking out multiple egg cells from the prospective mother by multiple ovulation technique. 15-20 egg cells are obtained by treating the mother with some hormones to enhance the ovulation (formation of fertilizable eggs) process. Next, the eggs are fertilized by the sperms of the prospective father. Then fertilized eggs are let to develop and divide until 8 cells stage.
At this stage one or two cells are removed from the embryo and they are further examined to assess the presence of any genetic defect. If any defect is found the embryo is not implanted back to the uterus of the mother. But if there is no defect in examined cells, we can be sure that nor there will be any defect in remaining embryonic cells that belong to same embryo. Thus that embryo is suitable to be implanted. However, a few cells are implanted out of 15-20 obtained eggs, because most of the eggs or embryos do not survive one of the processes or they are defective for the gene tested.
The controversy is mainly about these dying cells or embryos containing a few cells. Some people argue that these should be considered as complete human beings since they have the all required genetic information and cellular programme to form a complete human; and, thus, leaving them to die is something like killing a fetus by abortion. Others claim that a few cells cannot be taken as human beings. Sexing of the embryo is usually done in sex linked genetic disorders in which only males or females are defected. If you can choose the sex of the offspring before implanting the embryo you can prevent defective births.
However, it is possible to sex the embryo for just because the parents want it to be in a certain sex. Actually sexing to plan the family is done in some institutions. This is another controversial area. Should parents be let to choose the sex of their off springs? It is also possible to choose one trait of the embryo i. e. you can choose your off spring to be blue-eyed. Although the technology is not yet well developed to diagnose multiple genes it will soon. And once more we encounter the slippery slope of germ line gene therapy.