Human Genetic Screening

Michelle Dean

Copyright 1999

Genetic testing involves determining the genetic status of individuals that have symptoms or are at a high risk of developing a genetic disorder due to a family history of a heritable disease. Genetic screening is distinguished from testing because individuals without symptoms or a family history of a genetic disorder are assessed (McCarrick 1997, Kodish et al. 1998). Genetic screening is not aimed at targeted populations. Sometimes, the terms genetic testing and screening are used interchangeably. The number and availability of genetic tests will increase as the Human Genome Project continues. The project is expected to identify 50,000 to 100,000 genes present in the human genome. These identified genes will then be available as diagnostic markers for many genetic diseases. About 5,000 heritable disorders have been clinically characterized, and of these, about 800 heritable disorder genes have been sequenced (Caskey 1993). This genetic information is opening the door to testing for many genetic disorders, and both genetic testing and screening give rise to various questions dealing with such topics as morality and confidentiality. Genetic testing has five areas of focus which are prenatal diagnosis, newborn screening, carrier screening, forensic screening and susceptibility screening (McCarrick 1997). Susceptibility screening involves testing workers for susceptibility to workplace toxins that may cause future disabilities. Since some workers become disabled by occupational illnesses while co-workers are unaffected, those affected individuals are thought to possibly have a genetic predisposition. (McCarrick 1997). The remaining four areas of genetic testing will be examined in more detail.

Prenatal Diagnosis

Prenatal diagnosis examines whether or not a fetus is at risk for various genetic disorders. Amniocentesis can be used to find chromosomal abnormalities such as Downís syndrome and biochemical abnormalities at the genetic level. Up to 180 disorders, which include Huntingtonís disease, sickle cell anemia, and Tay-Sachs disease, can be detected (Nelkin 1993). Chorionic villi sampling can also detect several genetic disorders, and it can be done earlier in the pregnancy than amniocentesis. Other methods of prenatal diagnosis include ultrasound, which creates a fetal image on a screen, and fetoscopy which uses a camera inserted into the uterus to view the fetus. Another method, preimplantation genetic diagnosis (PGD), involves testing embryos for genetic disorders before in-vitro fertilization (IVF). More than 30 women in the U.S. and Europe have undergone PGD to ensure their children are free of genetic disorders (Grady 1995). For IVF, a woman is given hormones to stimulate her ovaries to produce many mature eggs at once. The eggs are surgically collected and fertilized with her partnerís sperm before being implanted into the womanís uterus. During the three day period when mature eggs are fertilized and before they are implanted into the uterus, one or two cells are extracted from each embryo for genetic testing. Embryos that carry defective genes can then be eliminated before implantation (Grady 1995).

Newborn Screening

Another area of genetic testing is newborn screening which detects genetic disorders early in infancy. Genetic disorders are estimated to occur in about 5% of all live births and to account for about 30% of all pediatric hospital admissions (Nelkin 1993). Several newborn screenings came into use in the 1960s and 1970s. These screenings include testing all newborns for phenylketonuria (PKU), African-American newborns for sickle cell anemia and Ashkenazic Jews for Tay-Sachs disease (McCarrick 1997). These tests utilize traditional methods of detection which may involve the detection of circulating metabolites or blood components. However, DNA-based methods are available to detect the genetic mutations underlying these disorders (Caskey 1993).

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).

Carrier Screening

A third area of genetic testing is carrier screening, which involves identifying individuals with a gene or chromosome disorder that may cause problems for the individual or for future offspring. With carrier screening, heterozygotes can be identified. Heterozygotes are often free of the disease, but have an increased risk of having affected children. Many disorders lend themselves to carrier screening such as sickle cell anemia, Tay-Sachs disease, cystic fibrosis, Duchenne muscular dystrophy, hemophilia, Huntingtonís disease and cancer (McCarrick 1997).

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).

Forensic Screening

The newest area of genetic testing is forensic screening, which seeks to determine a linkage between a suspect and evidence in criminal investigations. DNA evidence has been used in court cases to show guilt or innocence, and juries have based their verdicts on this type of information (McCarrick 1997). DNA can be called the ultimate identifier because it shows abundant variation, is present in all cells, and is a fairly stable molecule likely to be found in dried stains (Lander 1993). DNA from a suspectís blood and from an evidence sample are extracted. The DNA is then cut up by restriction enzymes and differentiated by gel electrophoresis. Radioactive probes are used to visualize the fragments, producing an autoradiogram for each locus examined. Then, a comparison can be made between the DNA patterns. Most DNA fingerprinting labs examine four highly polymorphic RFLPs called variable number of tandem repeats (VNTR) loci (Lander 1993). These four VNTR loci are believed to carry enough variability to draw conclusions about whether DNA from a suspect matches the DNA found at a crime scene.

Pros and Cons of Genetic Testing

Besides aiding in the conviction of suspects, genetic testing has several positive effects on public health. One positive effect is stated by Carol Krause (1998), a two -time cancer survivor. She states that the results of genetic testing can help people make decisions that might reduce the risk of getting or dying from cancer. Although many cancer predisposition tests may indicate an individual is not carrying a specific mutation in a cancer gene, the test cannot rule out the possibility of future development of the cancer. However, testing for cancer predisposition may still provide information that will allow an individual to reduce their cancer risk. For example, a positive test result for an inherited breast cancer mutation may lead to augmented screening or prophylactic measures (Kodish et al. 1998). Carol Krause (1998), while testifying before the U.S. House of Representatives Subcommittee on Technology, stated, "A test could help people make health care decisions. Iím not worried about guarantees here. Iím worried about improving the odds."

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.

My Opinion

Human genetic screening is going to become more available for a vast array of disorders as the Human Genome Project draws closer to completion. There are many issues that need to be addressed. I believe that prenatal diagnosis is justifiable as long as the risk to the mother and fetus does not outweigh the benefit of the information gained by the test. If prenatal diagnosis is undertaken for the purpose of early intervention or to allow time for the acceptance and preparation of a child with a defect, then it should be done. I do not feel that prenatal diagnosis should be undertaken with the option of abortion as a possibility. I feel strongly that abortion is morally wrong unless the motherís life is in serious jeopardy. Life needs to be respected from the moment of conception until natural death. My views are strongly influenced by my Catholic religion. Pope John Paul, when referring to selective abortion, stated in a recent encyclical: "Such an attitude is shameful and utterly reprehensible, since it presumes to measure the value of a human life only within the parameters of "normality" and physical well-being, thus opening the way to legitimizing infanticide and euthanasia." (Catholic Church 1996). I am fortunate to have two healthy children, and I declined prenatal testing beyond the usual procedures. I can understand how some individuals may choose for other prenatal testing, but I hope they will respect life and not measure it by earthly standards.

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.


Beardsley, Tim. 1996. Vital Data: Trends in Human Genetics. Scientific American. March. 274: 100-105.
Berger, Edward M. 1996. Morally Relevant Features of Genetic Maladies and Genetic Testing. In Gert, Bernard et al. Morality and the New Genetics: A Guide for Students and Health Care Providers. Jones and Bartlett Publishers: Sudbury, Massachusetts, pp. 167-187.
Caskey, C. Thomas. 1993. DNA-Based Medicine: Prevention and Therapy. In Kevles, Daniel J. & Hood, Leroy [Eds.] The Code of Codes.Harvard University Press: Cambridge, Massachusetts, pp. 112-135.
Catholic Church. 1996. National Council of Bishops. Committee on Science and Human Values. Critical Decisions: Genetic Testing and its Implications. United States Catholic Conference: Washington D.C.
Grady, Denise. 1995. Unnatural Selection. Vogue. October. 185:230-234. Hubbard, Ruth and Wald, Elijah. 1998. In Roleff, Tamara L [Ed.] Biomedical Ethics: Opposing Viewpoints. Greenhaven Press: San Diego, California, pp. 191-199.
Kodish, Eric, Weisner, Georgia L., Mehlman, Maxwell and Murray, Thomas. 1998. Genetic Testing for Cancer Risk. The Journal of the American Medical Association. 21 January. 279: 179-181.
Krause, Carol. 1998. Genetic Testing Can Save Lives. In Roleff, Tamara L [Ed.] Biomedical Ethics: Opposing Viewpoints. Greenhaven Press: San Diego, California, pp. 200-207.
Lander, Eric. 1993. DNA Fingerprinting: Science, Law, and the Ultimate Identifier.In Kevles, Daniel J. & Hood, Leroy [Eds.] The Code of Codes.Harvard University Press: Cambridge, Massachusetts, pp. 191-210.
Lerman, Caryn and Croyle, Robert T. 1995. Genetic Testing for Cancer Predisposition: Behavioral Science Issues. Journal of the National Cancer Institute Monographs.17: 63-65.
McCarrick, Pat Milmoe. Genetic Testing and Genetic Screening. Obtained from the WWW 8/27/99: September 1993/updated 1997:
Nelkin, Dorothy. The Social Power of Genetic Information. In Kevles, Daniel J. & Hood, Leroy [Eds.] The Code of Codes.Harvard University Press: Cambridge, Massachusetts, pp. 177-190.
Rothstein, Mark A. 1995. Genetic Testing: Employability, Insurability, and Health Reform. Journal of the National Cancer Institute Monographs.17: 87-90.
Sidransky, David. 1995. Molecular Markers in Cancer Diagnosis. Journal of the National Cancer Institute Monographs.17: 27-29.
Stern, Robert C. 1997. The Diagnosis of Cystic Fibrosis. The New England Journal of Medicine. 13 February. 336:487-491.
Vines, Gail. 1995. An Unsuitable Case for Treatment. New Scientist. 9 September. 147: 37-39.
Wexler, Nancy. 1993. Clairvoyance and Caution: Repercussions for the Human Genome Project. In Kevles, Daniel J. & Hood, Leroy [Eds.] The Code of Codes.Harvard University Press: Cambridge, Massachusetts, pp. 211-243.

Student Essay List

Course Homepage