The mutation that causes fragile X syndrome occurs when a small section of the genetic material within the gene is repeated too many times. Most unaffected people have between six to fifty repeats of the letters CGG in this section. When an individual has between 50 and 200 repeats, the person is a permutation carrier of fragile x syndrome. Carriers are usually not affected by the fragile X syndrome, but they are at a risk of affecting their children. When an individual has more than about 200 repeats, the code is disrupted and the gene shuts down and fails to make the protein FMRP it usually makes. It is not yet known how exactly the lack of this protein causes the symptoms of fragile X. However studies have shown that it may cause problems of communication among the neurons in the brain. Fragile X syndrome can be passed on from a carrier mother to her child. A pre-mutation carrier mom has a 50% chance of passing the gene to her baby during each pregnancy. Some children who inherit the abnormal gene will have a pre-mutation and they will not have the symptoms of fragile X syndrome. However, some children inherit the full mutation and show symptoms of fragile X syndrome. A male, who is a carrier of a pre-mutation in the fragile X gene, will pass on the pre-mutation to all of his daughters but none of his sons. The daughters generally have no symptoms of fragile X syndrome, but they are carriers of a pre-mutation that may be passed on to their children.
Children and adults have varying degrees of mental retardation or learning disabilities, behavioral and emotional problems including slurred or broken speech, inability to control anger and other emotions and sensitivity to loud noises. People affected with fragile X do not look much different from their peers. Some subtle physical characteristics of the disease include long, narrow face, prominent ears, large forehead, high arched palate, overly flexible joints and flat feet. Some males may also experience loose joints and enlarged testicles as they reach puberty. Young children with fragile X syndrome often have problems and delays in learning how to sit, walk and talk. Children with the syndrome may have frequent tantrums and difficulties paying attention. They often experience anxiety and depression and are overwhelmed by what is going on around them. The symptoms tend to be a lot more severe for males than for females.
Explain the basis of genetic testing.
Genetic testing is a sophisticated technique used to test for genetic disorders. Doctors can test patients for mutations that put them at high risk for hereditary forms of diseases such as breast and ovarian cancer. There are three main types of genetic testing: chromosome studies, DNA studies and biochemical genetic studies. The study of chromosomes is called ‘cytogenetics’. In order to be able to study chromosomes under a microscope, they are first stained. When stained, the chromosomes look like strings with light and dark bands. A normal female karyotype (a karyotype is a photo of the cell with all 46 chromsome) is written 46, XX, and a normal male karyotype is written 46, XY. The standard analysis of the chromosomal material evaluates both the number and structure of the chromosomes, with an accuracy of over 99.9%. Chromosome analyses are usually performed using a blood sample (white blood cells), prenatal specimen, skin biopsy, or other tissue samples. Chromosomes are analyzed by specially trained healthcare personnel that have advanced degrees in cytogenetic technology and genetics. These types of studies may be performed when a child is born with multiple birth defects. Chromosome studies may also be performed when people have certain types of leukemia and lymphomas, to look for specific changes in the order of the chromosome material associated with these types of cancers.
DNA can be analyzed either through direct or indirect studies. Direct DNA studies simply study the gene in question for an error. Errors in the DNA may include a loss of a piece of the gene's DNA (deletion), an alteration in a single unit or base pair of the gene's DNA (point mutation), or the repeated replication of a small sequence (for instance, 3 base pairs) of the gene's DNA (trinucleotide repeat). Different types of mutations are found in different disorders. The DNA needed for direct DNA studies is usually obtained by taking a blood sample. In cases where the gene that is mutated and that causes a condition has not yet been identified, but researchers know approximately where it lies on a particular chromosome, indirect DNA studies may be used. Indirect DNA studies are also used at times when the gene identified is too large for analyses. Indirect DNA studies involve using markers (markers are DNA sequences located close to or even within the gene of interest) to find out whether a person has inherited the crucial region of the genetic code that is passing through the family with the disease. Because the markers are so close, they are almost always inherited together with the disease. Indirect studies usually involve blood samples from several family members, including those with and without the disorder in question. This is to establish what pattern of markers appears to be associated with the disease. Once the disease-associated pattern of markers is identified, it is possible to offer testing to relatives to determine who inherited this pattern, and therefore who may be at a higher risk of getting cancer for example. The accuracy of the test depends on the closeness of the markers to the faulty genes. In certain cases, the test cannot give useful information to the healthy members, as there are no reliable markers available. Many of the cancer susceptibility genes that are known about today, were discovered through studies of markers of families who had multiple members with cancer.
Biochemical genetic testing involves the study of enzymes in the body that may be abnormal in some way. Enzymes are proteins that regulate chemical reactions in the body and therefore if some enzymes are deficient or absent, unstable, or have altered activity, it can lead to birth defects and abnormalities in adults. There are hundreds of enzyme defects that can be studied in humans. At times it can be easier and more efficient to study the enzyme that is defective rather than studying the gene mutation that is causing the enzyme to be defective. Biochemical genetic studies may be done from a blood sample, urine sample, spinal fluid, or other tissue sample, depending on the disorder. Another way of examining gene products, rather than the gene itself is through ‘protein truncation’ studies. Testing involves examining the protein made by a gene to see if it is shorter than usual. Certain mutations in genes can cause a protein to be truncated or shortened. With the protein truncation test, it is possible to measure the length of the protein the gene is making to see if it is the right size or shortened. These studies can be performed on a blood sample. These types of studies are often performed for disorders in which the known mutations predominantly lead to shortened proteins
There are a large number of specific genetic tests. For example prenatal diagnosis is the genetic testing of a fetus. Prenatal testing is used to detect changes in a fetus's genes or chromosomes before birth. This testing is offered when there is a risk of bearing a child with the genes associate with mental retardation or psychical deformities. Pre-natal diagnosis is carried out using biochemical, chromosomal, and DNA-based genetic test and is widely available for the prenatal testing of conditions such as Down syndrome. In some cases it can help couples make decisions about pregnancy. However, it must be kept in mind that the testing cannot identify all disorders. Another genetic testing frequently done as a preventive health measure is newborn screening. As the name suggests it is carried out on newborn infants. In the United States this the routine testing for certain disorders is the most common for of genetic testing. For example, all states in the US test infants for hypothyroidism (a condition where the thyroid gland does not function normally) that is present at birth and phenylketonuria (a genetic disorder that causes mental retardation if left untreated). Carrier identification includes genetic tests used by couples that are considering having a child but whose families have a history of genetic disorder, or who want to find out if they carry any diseases themselves that they might be at risk of passing on to their child. If both parents are tested, the test can give them information on the couple’s risk of having a child with a genetic disorder. This test is also used by people from a certain ethnic groups with an increased risk of developing certain genetic disorders. Three common tests include those for cystic fibrosis, Tay Sach’s disease and sickle-cell disorder. Predictive or pre-symptomatic genetic testing for late-onset disorders, which include adult diseases such as cancer and heart diseases are also available. These diseases can be caused by environmental as well as genetic factors. Pre-symptomatic testing can determine whether a person will develop a genetic disorder, such as Huntington disease (an inherited brain disorder that appears during mid-life), before any symptoms appear. The results of predictive and pre-symptomatic testing can help people make decisions about medical care. Another type of genetic testing is the pre-implantation genetic diagnosis, which is carried out on embryos that have been fertilized in the lab using routine IVF techniques. Pre-implantation studies are used following in vitro fertilization to diagnose a genetic disease or condition in an embryo before it is implanted into the mother's uterus. Embryos are tested for the presence of a specific gene, and only embryos without the gene are implanted into the mother's womb. However, this is not legal in all countries. Last but not least, forensic testing involves using DNA sequences to identify an individual, generally for legal purposes. This type of testing can help to identify crime victims, rule out or find a crime suspect and help to find out if a person is biologically related to another (for example paternity).
Discuss the ethical issues surrounding the widespread use of genetic testing. Include in your discussion use of IVF technology.
Genetic testing has already dramatically improved lives. Some tests are used to clarify a diagnosis and direct a physician toward appropriate treatments, while others allow families to avoid having children with devastating diseases or identify people at high risk for conditions that may be preventable. Even though the numbers of opportunities for disease prevention using genetic testing will increase with time, currently the value of genetic information is questionable when there are no proven interventions and testing brings with it a risks of insurance loss, employment discrimination, psychological harm and harm to relationships.
The potential for stigmatization prior to the onset of any symptoms creates cause for privacy concerns. Since the medical profession tends to circulate patient files to other doctors and insurers, it is difficult to monitor access to actual knowledge of genetic testing data. Furthermore, since genes are inherited and found not only in an individual but also in blood relatives, a genetic test involves many people and could invade the privacy of them all.
Some are concerned that employers will deny employment to those at high risk for such diseases as cancer, which can raise the cost of insurance and increase employer liability. Most companies, especially those that involve themselves in long term projects such as research, want employees that are going to be working there on a long term basis and that are going to be diligent. The days of absence taken by ill employees and high staff turnover could reduce their productivity and therefore their profits. Because of this employers may not want to employ people who have genetic predispositions to certain diseases or who already have genetic diseases. Many companies now physically screen employees before employing them to make sure they are healthy. They ask for the results of any genetic tests they may have taken or make them go through certain genetic tests. Still economic efficiency does not provide an adequate justification for discriminating against a person who has a predisposition for a disease. As explained before, just because a certain gene is prevalent in a person it does not mean that they will suffer from its symptoms. They may be just carriers. Yet again in some cases health assessments are in the public’s interests where disease in certain occupations would put third parties at risk, for example cases of Huntington’s disease and airline pilots.
Insurance is another area of concern for many. People known to carry a gene that increases their likelihood of developing cancer, for example, may get turned down for health insurance. Without health insurance, it may be impossible for some people to get treatment for a disease that could be fatal. However, if they are given health insurance, they are required to pay very high premiums. This may lead some people to decide against genetic testing for fear of what the results might show, and who might find out about them. It also could lead some people to decline participation in biomedical research such as studies of gene mutations associated with certain diseases that examine the history of families prone to such disorders. Some scientists and legislators have suggested that genetic information should be taken off the table in order to prevent genetic discrimination. However insurance companies quickly realized that current, acceptable, underwriting tests (such as cholesterol tests, height and weight measures, and family history questions) fell within some definitions of genetic testing. So, the elimination of the use of “genetic” information would necessitate structural changes to the industry and result in the insured having more information than the insurer. Insurance companies generally believe that they should have access to this genetic information. They argue it is just like any other medical information and is needed for the insurance company to properly assess its risks. Being a commercial industry, it is the perspective of the insurance companies that they are responsible to generate profit for their stockholders, and that it is no more their responsibility to ensure access to care than any other private business.
The concerns go beyond insurance companies and employment though. Many people are struggling with other uses of knowledge acquired from the results of genetic tests. Genetic tests are limited in a lot of ways. Although they can identify problems with a gene, they may not always be efficient in predicting how severely a person’s life may be affected because of the defect. Although some people carry certain mutations that are associated with a disease, they may never end up developing it and this points to the difficulties that arise from trying to interpret positive test results. Often, even though a person is diagnosed with a genetic disorder, there is no treatment available for it. Thus the patient is left knowing something is wrong but with no options to correct it. As a result many people prefer not to take the test and not to find out if they have a disorder, as they feel that since there is no cure they will only end up ruining their psychological and emotional well being. Knowing that one carries a disease gene can cause depression or anger especially if there is no cure available for it. Knowing might cause guilt, anxiety, impaired self-esteem, social stigma, and possible insurance and employment discrimination. It may also affect decisions to have children. For example, a pregnant woman who is informed that she has a gene that almost always causes breast-cancer in adulthood and that her baby is carrying the gene as well, is faced with an extremely difficult decision on what to do with this information. Should she abort the baby to prevent a treatable disease that the baby won’t even experience until adulthood or should she go ahead with the pregnancy. In case decides to go ahead with the pregnancy, it is likely that she will be plagued with worries on how she would (if she decides to at all) tell her about her problem and if she does tell her, what kind of life her child can lead knowing that at some point in her life she will get cancer. As mentioned before, screening for diseases such as phenylketonuria is regulated in almost all the states of the United States. These types of screens are looked upon positively since the knowledge can be used to provide the child with the proper diets, treatments, or necessary care. However there are also concerns that parents will use prenatal screening as a form of selection for the "perfect child" and chose to abort any fetus that doesn't fit their standards.
In vitro fertilization techniques were initially adopted for the treatment of couples in which the female suffered from tube blockage, which could not be treated. However, in time, with more research it became evident that a wider range of infertility problems could be treated by in vitro fertilization (IVF). The concept of IVF is simple. A ripe human egg is extracted from the ovary, shortly before it would have been released naturally. The egg is then mixed with the semen of the partner so that fertilization can occur. The fertilized egg, once it has started to divide, is then transferred back to the mother’s uterus. Normally, more than one embryo is transferred to a potential mother, so as to give her a better chance of achieving a pregnancy, since at times natural problems such as the egg not attaching to the wall of the uterus can occur. One application of IVF other than as a treatment for infertility is in the area of preimplantation embryo diagnosis. This technique aims to avoid the patient’s ordeal about the decision to undergo an abortion once an affected fetus is diagnosed by the more conventional techniques of prenatal diagnosis. The technique takes advantage of the access to embryonic material with the aim of diagnosing a chromosomal abnormality in an embryo. This, theoretically, allows the transfer of non-affected embryos back to the patient. The advancements in human IVF technology increases the options for treatment of infertile patients and those with inherited severe genetic disease. However, these developments test moral and ethical attitudes within the community. Many people frown upon the practice of in vitro fertilization.
Certain ethical problems have been raised due to technology being developed which has enabled the extracted embryos to be frozen. (some couples wish to freeze their embryos until a later date for varying reasons including carreer advancement). A stored embryo becomes an object which is "shelved," to be used at our convenience. A further concern is whether there is the risk of abnormalities to the future child. Many people are against the use of frozen embryos that are no longer needed by the mother for research (for example stem cell research). The destruction or damaging of some embyros during the course of research is a rigorosly contested issue. Some groups protest that these embryos have the right to life, and that they are just as much human beings as they are. Many christians regard it as abortion when embryos are disposed of instead of being implanted in the womb. Other ethical issues concern the well emotioanl and psychological wellbeing of the child. Some people feel that it will be unhealthy for the child when he learns how he was delivered. Some people argue that the child may feel inferior and inadequate if he finds out that the was not concieved through natural methods. The use of IVF provides a greater range of options for single people and same-sex couples wishing to have children. Although both groups already raise children, IVF makes the option much simpler and could make the option widespread. Once again some people object that this could give psychological problems to the child if they grow up without a mother/father role-model. Also, a lot of times the child grows up not knowing who his real father is, because often for single mothers have not met the sperm donners. In one case in 2001 a French woman received a lot of publicity as she had played the role of her brother’s wife in order to give birth to have an egg fertilised by him. Some people considered this to be incest and found it highly unethical. On a purely theological level, IVF tends to interfere with the general religious idea that only God can create children. Therefore, many religious people oppose the concept strongly.
