CASE STUDIES IN GENETIC SCREENING
1992 Woodrow Wilson Biology Institute
The following is a simplified simulation of genetic screening for four
specific mutations and a suggested format for exploring the different ethical
issues that might result from such genetic testing.
This activity is appropriate for advanced and AP biology students after
some explanation and study of DNA biotechnology techniques, specifically
restriction enzyme digests, gel electrophoresis, blotting, hybridization with
probes, and autoradiography.
It is known that many genes are linked very closely to and inherited with
specific identifiable base sequences of introns. Detection of this marker
sequence is evidence of the normal allele. Conversely, the absence of the
marker or its presence in an abnormal banding pattern of a DNA fingerprint is
evidence of a mutation in that specific gene.
In the following simulation, four samples of "normal" DNA have
been digested with four different restriction endonucleases, separated in
agarose gel, and stained, resulting in four different banding standards. The
fingerprints are transferred to a nylon filter using a Southern blot
technique, and each standard is labeled with a different radioactive "
probe" that hybridizes with a specific marker gene. An autoradiograph
now points to the band of DNA fragments containing the marker-probe hybrid and
the gene of interest to which it is linked.
Individual fingerprints prepared similarly might place a specific marker-
probe in a band of different fragment lengths for those genes containing a
sequence mutation, or the marker may be missing altogether if a deletion in
the marker-gene sequence has occurred.
Divide the class into groups of 3-5. Each group receives a copy of the
standards, one of the four sets of fingerprints, and a role-playing scenario.
The fingerprints should be carefully compared with their corresponding
standards to determine if an inherited abnormality is indicated.
After the abnormality has been determined, each group can be charged with
researching the background of their "inherited" mutation, or the
teacher may opt to give them that information (included here). Roles can be
assigned within each group according to the scenario, and the students should
be prepared to "role-play" on a teacher-moderated panel at a
future date. On the day of the role-playing activity, one member of each
group should give a brief overview of their specific abnormality to the whole
class. Other inheritable diseases can be used, depending on the relevance to
the ethic and economic make-up of the class, for example, Tay-Sachs or sickle-
Note: The third banding pattern on each group handout is the abnormal one. The teacher should note to the students that while a radioactive probe is used to detect the specific genetic marker, these simulated fingerprints do not show the probe. Also, the questions are meant to "build" an ethical situation and should not be given to the students until asked by the moderator.
- Family physician
- Married couple A
- Husband whose brother has cf
- Wife with no family history of cf
- Married couple B with 1 cf child, expecting another child
Cystic fibrosis is an autosomal recessively inherited disease resulting in
the secretion of thick, abnormal mucous in the lungs and pancreatic
insufficiency. The range of seriousness of the disease is broad, but most
children require extensive medical treatment and daily multiple respiratory
therapy. The disease is progressive, with about 40% of cf patients living to
the age of 30.
Cf is the most frequently inherited genetic disorder among American
children. It affects 1 of every 2500 children; 30,000 currently have the
disease. Cf can be caused by any one of over 100 different mutations known to
occur on the cf locus on chromosome 7. 75% of all cf cases result from a
single mutation that is easily screened. The other 25% of cases result from
other mutations, most of which can not be tested. One in twenty (12 million)
Americans carry 1 mutation on the cf locus; that is, they are heterozygous for
the cf mutation.
SUGGESTED QUESTIONS TO INDIVIDUAL PANEL MEMBERS:
Do you suggest screening for all of your couples who are planning to
have children? Why or why not?
You can detect only 75% of cf carriers. 1 in 400 families will have both
parents as carriers. Do you offer genetic screening when you can't screen
everyone because the technology isn't there yet?
The cost of screening is several hundred dollars plus the cost and time of
genetic counseling to explain the results and risks. Who should pay for this
What if Couple B can't pay and insurance won't?
Do you want to be screened? Why or why not?
You decide to be screened. The husband shows positive (has a cf mutation)
and the wife does not. There is still a 25% chance that she has a mutation
that doesn't show up. You have a 50% chance of having a child that has the cf
mutation. Do you want to have a baby?
You get pregnant. Do you have the fetus screened? Odds are 1/300 to
1/500 that the baby will have cf. Do you abort?
Do you want your fetus screened? Why or why not?
Are you going to abort if the child shows positive?
If yes, what does this say to the affected child you already have?
If no, why are you screening?
FAMILIAL HYPERCHOLESTEROLEMIA (FH)
- Personnel Director of University
- Wife (1 child, age 18)
Familial Hypercholesterolemia (FH) is an autosomal dominant mutation
resulting from a deletion in a segment of chromosome 19. Inheritance of the
mutation results in the selective increase in blood levels of LDL cholesterol,
resulting in premature atherosclerosis, and may result in early heart attacks,
progressive cardiovascular disease, and death. Early detection and treatment
can greatly prolong and enhance life.
SUGGESTED QUESTIONS TO INDIVIDUAL PANEL MEMBERS:
You're 38 years old, have just finished a Post-doctoral Fellowship, and
have a firm job offer at a prestigious university. You have a serious heart
attack. Your family history shows heart disease at early ages in several
family members. The doctor wants to screen you for FH. Do you let him? Why
or why not?
Screening shows the presence of FH. The university is waiting to hear of
your decision on employment. Do you tell them of the heart attack? Do you
tell them of the screening? Why or why not? What values are at stake here?
How do you feel about telling the university the full story?
Do you want your child screened?
What are the advantages and disadvantages of the child's being screened?
What will this do to his chances for a job, insurance, marriage?
You are told of the heart attack. Do you insist on a screening before
hiring this man?
If you know of a positive screening, do you hire anyway or withdraw the
offer? Explain your reasons. What values are involved here?
- Wife whose mother has Huntington's
- Son, age 20
- Fiancée of son
Huntington's Disease is caused by an autosomal dominant mutation in
chromosome 4. It manifests in adults between the ages of 35-42 as progressive
involuntary choreiform movements and dementia due to premature loss of
neuronal function in the brain. It is inevitably fatal. Most carriers show
signs of depression before the onset of early symptoms which include
irritability, impulsiveness, erratic behavior and lethargy. There is no
A person "at risk" for Huntington's is automatically rejected
for health insurance. The cost of a genetic screening for the disease is
about $5,000 and is a very emotionally stressful procedure.
SUGGESTED QUESTIONS FOR INDIVIDUAL PANEL MEMBERS:
Your mother has had Huntington's for years and is totally dependent on
your father to care for her. You realize you have a 50% chance of developing
the disease. Do you want to be screened?
Why or why not? (Remember: costs, psychological stress of not knowing,
attitude of your child to knowing, stigmatization by family, friends, and
What do you advise your son?
You are contemplating a job change because you don't get along with your
boss. However, this will require applying for new health insurance. Are you
obligated to mention this history of disease in your family?
You've seen how this disease has affected the life of your grandparents. Do
you want your mom screened? Why?
Your mom is screened and is found to be carrying the gene. What do you
tell your fiancée? Do you plan to have children? Should you be
How do you feel about the possibility of your future husband's developing
Huntington's? Is the wedding still on? Will you have children? What values
are involved here?
Your fiancée is screened and is found to be carrying the disease.
Does this change the way you feel about marriage?
- Husband with mild NF1
- Wife (pregnant)
- Genetic Counselor
Recklinghausen Neurofibromatosis (NF1) is an autosomal dominant mutation
of chromosome 17. Usually during adolescence, symptoms will appear and will
increase in severity with age. If the disease is present in childhood, it can
lead to severe disfigurement with considerable physical and emotional
suffering, and is sometimes referred to as "Elephant Man" disease.
There is much clinical variability, however, in the manifestation of this
disease, even within nuclear families. Symptoms range from lightly pigmented
areas of normal skin (called cafe-au-lait spots) to severe disfigurement due
to nerve tumors. Other symptoms may include macrocephaly, learning disorders,
mental retardation, short stature, scoliosis, seizures, hypertension or
headaches. Two thirds of NF1 patients lead physically normal lives. Life
span is normal except in those cases predisposed to certain cancers.
NF1 can be screened by looking for the translocated marker that is
inherited with the NF1 mutation.
SUGGESTED QUESTIONS FOR INDIVIDUAL PANEL MEMBERS:
You have been diagnosed with NF1, a disease that is not clearly
manifested. You and your wife are expecting your first child after 3 years of
visiting fertility specialists. What do you do? Is abortion a
consideration? Why or why not?
Will you consider fetal screening? (There is a small risk of spontaneous
abortion after screening.)
The baby is screened and found to carry the disease. Is abortion an
option? What about the right of the child not to be born?
This couple comes to you after fetal screening, and is leaning heavily
toward abortion. Do you tell them that they may be terminating a very healthy
You know this couple is firmly against abortion in any circumstance. Do
you prepare the couple for all possibilities, including a worst case scenario?
Ager, Susan and Linda Hales. "Geri's gamble". The Washington
Post, June 13, 1989, pWH12.
Bertolini, Stefano, et al. "A large deletion in the LDL receptor
gene - the cause of familial hypercholesterolemia in three Italian families:
a study that dates back to the 17th century." American Journal of Human
Genetics. July 1992, v.51(1):123-34.
Gusella, James F. "Huntington's Disease." Advances in
Human Genetics. 1991, v. 30:125-147
Kolata, Gina. "Some doctors deplore move to test for gene for cystic
fibrosis." The New York Times. May 22, 1990, p.B7.
Tsui, Lap-Chee and Manual Buchwald. "Biochemical and molecular
genetics of cystic fibrosis." Advances in Human Genetics
. 1991, v. 20:153-240.
Waldholz, Michael. "Cystic fibrosis gene testing nationwide runs into
technical and ethical barriers." The Wall Street Journal.
March 7, l990, pB4.
Wallace, Margaret R. and Francis S. Collins. "Molecular genetics of
Von Recklinghausen neurofibromatosis." Advances in Human Genetics
. 1991, v.20:267-296.
Wertz, Dorothy, et al. "Attitudes toward the prenatal diagnosis of
cystic fibrosis: factors in decision making among affected families."
American Journal of Human Genetics, May 1992, 50(5):1077-85.