An example of a disease that can now be tested for by DNA-based methods is cystic fibrosis. It is an autosomal, recessively inherited disease which results in pancreatic enzyme deficiencies and lung abnormalities. The gene responsible for cystic fibrosis, CFTR, was identified in 1989 and found to be on the long arm of chromosome 7. DNA-based tests are now available for families with a history of cystic fibrosis (Vines 1995, Stern 1997). However, identifying a personís genotype cannot alone be used to diagnose or rule out cystic fibrosis due to the number of mutations possible in the CFTR gene (Stern 1997). In order to test for cystic fibrosis using DNA-based methods, the number of mutations and which mutations to test for must be decided. Over 400 mutations have been found for CFTR, and each mutation requires its own gene probe (Vines 1995). Commercially available probes currently test for only 70 mutations of the over 400 mutations. Although these tests will detect more than 90% of all cystic fibrosis genes, the failure to find two abnormal genes does not rule out the disease. In approximately 1% of individuals with cystic fibrosis, no abnormal gene will be found, and in approximately 18% of individuals with cystic fibrosis, only one abnormal gene will be found (Stern 1997). Due to this large number of possible mutations within the cystic fibrosis gene, although penetrance is 100%, expressivity is variable, which implies that individuals with the same genotype may not experience the same range of severity of symptoms (Berger 1996).
Other diseases in which DNA-based methods for detection have been developed include some single-gene disorders such as Duchenne muscular dystrophy ( DMD), Lesch-Nyhan syndrome and ornithine transcarbamylase (OTC) deficiency. These diseases can now be detected using recombinant methods such as the polymerase chain reaction (PCR). Samples can be screened for deletions in the DMD gene by using multiplex PCR, which can detect 81% of the deletions in this gene (Caskey 1993). Multiplex PCR is also performed to detect mutations in the HPRT gene which is responsible for Lesch-Nyhan syndrome. However, after multiplex PCR the material is sequenced to detect mutations. The mutations that lead to OTC deficiency are too large to sequence in order to detect mutations, so PCR is used to generate single-stranded DNA from both normal and patient samples. These pieces of single-stranded DNA are then hybridized together to detect mutations (Caskey 1993).
Huntingtonís disease (HD) will be examined first. HD is an autosomal, dominantly inherited disease and symptoms do not occur until mid-life. It is a neuropsychiatric, degenerative condition that has no treatment. Linked polymorphic DNA markers allow for the detection of carriers of the HD disease allele (Wexler 1993). The genetic marker known as G8 was found when scientists were studying the DNA extracted from blood samples of two different families. The DNA was sliced up with restriction enzymes. Then, markers, restriction fragment length polymorphisms (RFLPs), were developed. When the DNA fragments were put on a gel with different radioactive markers, it was found that the marker G8 was able to hybridize with individuals who had the disease but not with healthy individuals. Eventually the G8 marker was linked to chromosome 4. The gene for HD has not been found to exhibit genetic heterogeneity where the gene could be on several different chromosomes. The gene for HD has been found on the top of chromosome 4 in over 100 families, so G8 and other newly found markers can be used to identify carriers of the HD gene before symptoms appear (Wexler 1993).
DNA diagnostics, the ability to identify particular DNA sequences by hybridization between a genetic marker and target DNA, can be used to identify not only carriers of single gene disorders such as Huntingtonís disease, but also the presence of dominant or recessive oncogenes that may predispose an individual to cancer (Hood 1993). Cancerous tumors have been shown to arise by mutations in some oncogenes, and some critical oncogene targets have been associated with certain types of cancers. These detectable genetic changes may be used as markers for early cancer diagnosis (Sidransky 1995). PCR-based techniques allow the analysis of tissue and body fluid samples for the detection of cancer predisposition. For example, mutations in the ras oncogene are believed to have a role in colon cancers, and mutations of the BRCA1 and BRCA2 genes are associated with breast cancer (Sidransky 1995, Kodish et al. 1998). Major limitations of screening for cancer predisposition involve allelic heterogeneity in which there are many different mutations in an oncogene and genetic heterogeneity in which there are many possible genes leading to the cancer. For example, inherited forms of breast cancer exhibit this allelic and genetic heterogeneity (Kodish et al. 1998). A possible solution is to examine microsatellite alterations (Sidransky 1995). Microsatellites are clusters of repeated sets of 2, 3, or 4 bases that significantly differ from individual to individual unless the individuals are related, and certain "hypermutable" microsatellites have been used as markers for colorectal cancer (Sidransky 1995).
Some genetic testing has gone beyond providing information for the individual patient to use and has led to therapeutic interventions and to helping couples make reproductive decisions. For example, the identification of abnormal genes for cystic fibrosis has led to earlier and more aggressive introductions of antibiotics, pancreatic enzyme therapies, and physical therapy, which have significantly helped affected individuals (Wexler 1993). Genetic testing can also help individuals in making reproductive decisions. Since there are several genetic disorders, such as Huntingtonís disease, cystic fibrosis, and Duchenne muscular dystrophy, that have no cure but are detectable by carrier screening, individuals can use this information when deciding whether or not to have children (Caskey 1993). Screening programs provide genetic information which has enabled individuals to participate in therapeutic options and has helped couples make informed reproductive decisions.
With all this useful information comes some major privacy concerns. Genetic testing can provide useful information for not only the patient, but also for others. There are many issues involving the confidentiality of genetic testing results. A major area of concern is the loss of insurance or employment. This fear is real, as demonstrated by patients who decline genetic testing for themselves and their children even though the testing might provide a medical benefit (Beardsley 1996). Families with a history of Huntingtonís disease have been denied insurance coverage. Also, families with a history of polycystic kidney disease have reported not having their children tested, for fear of them becoming uninsurable even though testing for PKD1, the gene responsible for polycystic kidney disease, can lead to therapies in some cases (Beardsley 1996).
The fear of loss of insurance is a real concern for many individuals that may consider genetic testing. Currently 85% to 90% of individuals with private health insurance are covered under a group insurance plan that is mainly provided by an employer (Rothstein 1995). Health care costs are on the rise. The cost of health care per employee has doubled in six years, and not all employees are equal in their rate of consumption of health care benefits (Rothstein 1995). These statistics imply that if employers could determine which employees were more likely to develop inherited genetic diseases, then coverage could be limited. Currently, some at risk individuals are required to pay higher premiums. Also, genetic testing information could be useful before hiring individuals since an individual with a genetic predisposition for a disorder may significantly utilize their health care benefits or a carrier of a genetic disorder may have offspring that require a disproportionate amount of medical benefits. Already about half of American employers require pre-employment medical exams (Nelkin 1993).
Susceptibility testing also raises concerns for employees. These tests can be thought of as a way to protect workers, but can also be viewed as a way to exclude employees that are most vulnerable to environmental work conditions, and thus avoid costly work environment changes (Nelkin 1993). Employers have utilized the term "hyper-susceptibility" to explain why some workers respond to dust and other contaminants more than the average worker (Hubbard&Wald 1998). Hiring discrimination based on these tests is another area of concern.
The testing of minors is another area of concern for genetic testing. This area of concern is a result of testing for Huntingtonís disease. Genetic counselors have formed a strong consensus that testing for HD in minors does more harm than good since there is no available therapy or cure, and HD does not strike an individual until mid-life (Beardsley 1996, Wexler 1993). Parents still seek testing for their minor children based on reasons of future financial planning. Some parents have requested testing to avoid spending money on a college education if a child is going to succumb to HD (Beardsley 1996, Wexler 1993). The principle U.S. testing lab, Helix, reported that 23% of their labs capable of testing for HD had done so on children under 12 years of age (Beardsley 1996). Genetic counselors want restrictions for the testing of minors, not adults.
The genetic testing of children, as well as adults, not only provides useful information to the patient, but may also lead to the development of more narrowly defined social categories and impacts the definition of the "normal" condition. Testing may be used to preserve existing social arrangements or to aid in certain groups having control over others (Nelkin 1993). American culture is perceived as having a preoccupation with testing, and there is a worry that complex human behavior is simply explainable biologically or genetically. Genetic tests can be perceived as powerful tools due to their apparent certainty (Nelkin 1993). In the press, such traits as mental illness and homosexuality have been attributed to genetics, and the environmental factors are being ignored (Nelkin 1993, Hubbard&Wald 1998). Through genetic testing, individuals may be perceived as normal if testing indicates no genetic defects or abnormal or defective if genetic mutations are found (Hubbard&Wald 1998). A third category may also arise titled "pre-symptomatic ill" due to carrier screening (Nelkin 1993). Disability advocates and feminists have come out against genetic testing because testing may aid in the belief that some individuals are less than perfect (McCarrick 1997).
Another disadvantage of genetic screening is the limitations of DNA fingerprinting. The belief in the credibility of genetic testing is demonstrated by the rapid acceptance of DNA fingerprinting. In theory, DNA fingerprinting is flawless because if enough sites of genetic variation are examined, two samples can be determined to either be from the same individual or not. However, in practice, DNA fingerprinting has been found to have problems. These problems become evident when DNA fingerprinting is compared to DNA medical diagnostics (Lander 1993). DNA diagnostics involves the testing of fresh samples under optimal laboratory conditions, and, if tests results are ambiguous, then more samples from the patient must be obtained. DNA fingerprinting requires scientists to work with whatever samples have been found at the crime scene. These samples may be degraded or may be mixtures from several sources. Often the scientist may only have enough sample to run one test so if the test is ambiguous, it may not be repeated (Lander 1993). Although DNA fingerprinting is a powerful tool, it has limitations.
DNA fingerprinting also gives rise to another issue, genetic banks. DNA data banks exist, and there is considerable concern about their growth. Currently the FBI has a data bank containing DNA fingerprints of paroled ex-convicts (Nelkin 1993). The military is interested in using DNA identification for all its military personnel (Lander 1993). The creation of a national DNA database of all newborns has been suggested in order to aid in the identification of kidnaped children (Lander 1993). Once any type of DNA database is established, many questions arise. What information will be contained in the database? Who will have access to the database? How secure will the database be? Privacy concerns are a major disadvantage to genetic testing programs.
Lastly, an important point is that genetic testing cannot stand alone. Physicians and genetic counselors need to be informed about genetic testing so that they can inform patients of the tests available and explain the results to patients so patients can make informed decisions ( Berger 1996, Reilly 1995). Genetic testing needs to proceed with patients understanding the limitations of tests, or patients are more likely to experience psychological distress (Lerman&Croyle 1995). Testing needs to be done under the supervision of physicians and counselors since results of some tests, such as HD, can be devastating to the family, and cancer predisposition can be difficult to comprehend (Reilly 1995). In some cases, individuals are not being properly informed. More than 40% of Helix laboratories reported having performed tests for patients directly without the involvement of a physician (Beardsley 1996). Also, genetic information can easily be misinterpreted. For example, a common misinterpretation of genetic information involves the belief that at least one person in each family will be affected (Wexler 1993). Genetic testing is a powerful tool, but privacy issues must be addressed and the patient must have knowledgeable health care professionals working with them.
I have serious reservations about preimplantation genetic diagnosis ( PGD), that stems from in vitro fertilization. Again, I am fortunate to have had two children and can sympathize with women unable to have children. In vitro fertilization may seem to be an option for those with financial means, but embryos are produced that may or may not be given the chance to develop. My opinion is that life should be treasured from the moment of conception. If embryos are produced in sterile laboratories and some are implanted in women, what becomes of the others? In the case of PGD, embryos are genetically tested and those found to be defective are discarded. In my opinion, this scenario does not show respect for human life.
Newborn screening is widely carried out for a variety of disorders and has proven to reduce the incidence of several genetic conditions like PKU. When newborn screening is carried out for diseases that can be cured or treated, it is a blessing. Genetic testing needs to benefit the individual being tested. This is a goal I have noticed over and over in the literature on genetic testing that I reviewed for this paper. With this goal in mind, I agree with many genetic counselors that minors should not be tested for conditions in which there is no cure or even a therapy. The knowledge that a child has Huntingtonís disease, for example, does not benefit the child in any way, since there is no therapy to improve or delay symptoms.
I believe the information that can potentially be gained from the genetic testing of consenting adults outweighs any negative aspects. The more information an individual has, the more informed decisions they will make. However, I do not feel that just anyone should be able to order a genetic test. Patients undergoing genetic testing need to have the limitations of the various tests explained completely. Many patients will require counseling after undergoing testing. For example, if a patient turns out to have Huntingtonís disease, there will be a lot of psychological stress. Perhaps a couple might undergo genetic testing and find out they are carriers of a genetic disease. This couple may then require genetic counseling to understand their options. Also, the results of tests for cancer predisposition are complicated since the causes of cancer are not well understood. I feel genetic testing should be the option of the patient, and the patient who chooses testing needs a support group of physicians and counselors.
If patients decide to undergo genetic testing, and since genetic testing should be for the benefit of the individual undergoing the testing, then I strongly believe that the results of genetic tests should be kept confidential. Keeping the results of genetic testing confidential needs to be a top priority. If it is not, I do believe there will be a large segment of our population that may become a genetic underclass. People may be labeled as defective, uninsurable or jobless. The number of laws addressing the protection of genetic information seem to be few. For this reason I believe privacy needs to be moved to the forefront of the genetic testing issue.
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