Genetics Case Study

“In Sickness and in Health” by Barry Chess Page 

Part I—Pedigree Construction
Greg and Olga were both a little worried. Starting a family presented choices and responsibilities far more long-
reaching and complex than anything either of them had encountered before, and sitting here in the reception area
of the genetic counselor’s offi ce they were beginning to feel the pressure. Th ey had met four years earlier in the
hemophilia clinic where Greg was waiting for his brother Jeff to get an injection of factor viii, a protein that helps
the blood to clot. When a person’s factor viii level is very low (less than  of normal), even the smallest cuts can be
troublesome and uncontrolled internal bleeding is common. Complications include swelling, joint damage, and an
increased likelihood of neurological complications due to intracerebral bleeding. Even simple surgical procedures such
as tooth extractions become far more risky. Jeff ’s condition was noted by his pediatrician shortly after birth when his
circumcision bled profusely. Since then, Jeff has received monthly injections of factor viii, either at home or (twice a
year) at a clinic where his physical condition is reviewed by a physician’s assistant. At fi rst these injections contained
clotting factor isolated from the blood of human donors but, for the last  years or so, he has received recombinant
clotting factor, which is genetically engineered.

It was in that clinic waiting room that Greg struck up a conversation with Olga, who was waiting for her uncle to
fi nish his exam and receive an injection of clotting factor. Like Jeff , Olga’s uncle also suff ered from hemophilia A due
to factor viii defi ciency. Beginning with this common experience, Jeff and Olga quickly fell in love and were married
the following year.

Th ey are now thinking about starting a family of their own, but are concerned about the risks of passing on genetic
diseases to their children. Th ey know for example that hemophilia A is an inherited disease, and several of Greg’s
relatives suff er from myotonic dystrophy, a muscle weakening disease that also runs in families.

As a fi rst step, the genetic counselor has asked them to fi ll out a narrative history listing their relatives, relationships,
and if they were aff ected by any genetic diseases that they know of. Th e forms are seen below.

NAME: Greg
I have one brother and one sister, neither of whom are married. My brother
suffers from factor VIII deficiency, but no one else in my family does. My
mother has two brothers and one sister. One of my uncles and one of my aunts
are affected by myotonic dystrophy. My affected aunt married an unaffected
man and they have a young, seemingly unaffected daughter. My other uncle is
unaffected, as is my mother. Our primary care doctor has said that because
both my mother and uncle are over fifty years old and show no symptoms, they
do not have the disease. My father is completely normal. He was adopted from
an orphanage and nothing is known about his family. My maternal grandmother
was an only child who also suffered from myotonic dystrophy. Her husband (my
grandfather) was one of seven children (four boys and three girls). No one in
the family seems to know much about the health status of my grandfather or his
brothers. Both of my parents are alive but all of my grandparents are deceased.

In Sickness and in Health:
A Trip to the Genetic Counselor
by
Barry Chess
Natural Sciences Division
Pasadena City College, Pasadena, CA

“In Sickness and in Health” by Barry Chess Page 

NAME: Olga

I have two brothers, one of whom has factor VIII deficiency. The brother
with the disease is married to a woman who does not have the disease.
They have two young boys, both normal. My father is an only child
who does not suffer from anything and his parents also are only
children who do not suffer from any diseases. They are all still
living. My maternal grandmother is healthy and had a sister who
died just after birth. She married my grandfather who was one of four
children, all boys, none of whom were affected by any disease that
anyone is aware of. My grandparents had two children, my mother
and my uncle. My uncle has hemophilia but my mom doesn’t. My
uncle married my aunt (who is unaffected) and they had two children,
neither of whom showed any sign of any disease. Their boy is still
single but their girl got married, to a normal man, and had a son, who

has hemophilia A.

“Good afternoon” said the woman rising to greet them, “I’m Dr. Ciletti. It’s good to fi nally meet you in person.”

“Nice to fi nally put a face to the voice. I’m Greg and this is my wife Olga.”

“Nice to meet you,” Olga said, taking a seat across the desk from Dr. Ciletti. “Th is whole having-kids thing is more
nerve-wracking when you really start to think about it.”

“You’re doing exactly the right thing. Th ere is no sense in worrying about things unless you have to. Maybe I can
set your mind at ease a little bit. To begin with, I know that you’re both concerned about factor viii defi ciency and
myotonic dystrophy because of the family history. Is there anything else that you’d like to know?”

“Well,” began Olga, “the fact that we both have these diseases in our family and there is a chance that we could pass
them on to our children has opened our eyes a little bit, but we’d also like to know if you can predict other diseases
that don’t run in our family. Like my best friend in high school had cystic fi brosis and she died when she was only
twenty four, and was sick almost all the time.”

“Okay, well, cystic fi brosis doesn’t look like it is in either of your family histories so it’s probably not worth worrying
about. But, we can spend a little time going over the chance that you both carry a gene that has never before shown its
face. Th e fi rst step is we have to convert the family information you two have provided into a graphical representation
called a pedigree. From there we can begin to correlate family relationships with the appearance of specifi c diseases.”

Question
. What would a pedigree of Greg and Olga’s families look like? Concentrate simply on family relationships

and aff ected persons.

Reference
Human Genetics for First Year Students: Pedigree Construction

http://www.uic.edu/classes/bms/bms655/lesson3.html

http://www.uic.edu/classes/bms/bms655/lesson3.html

“In Sickness and in Health” by Barry Chess Page 

Part II—Autosomal Dominant Traits
“Great, so this looks like an accurate representation of your family, right?” Dr. Ciletti asked.

“Looks good to me,” replied Greg.

“My family is so small, there’s not much to miss until you get to my grandparents,” said Olga.

“Well, factor viii defi ciency and myotonic dystrophy are inherited in completely diff erent ways. Come to think of it,
you asked about cf as well and …”

“cf?” asked Greg.

“Cystic fi brosis,” Dr. Ciletti continued. “I was about to say that cystic fi brosis is inherited in a manner diff erent than
both of the other diseases you are concerned about, but let’s tackle them one at a time.”

“Myotonic dystrophy is an autosomal dominant disease and it is the easiest to pick out of a pedigree. Now Greg, even
though you have an uncle and aunt as well as a grandmother who all have the disease, you don’t and there is no way
that you will pass this disease on to your children. So that is the fi rst piece of good news.”

“But don’t a lot of genetic diseases skip a generation?” Greg asked. “And even if doesn’t, my mom has two siblings with
the disease. Could she be a carrier and just pass the disease on to me? For that matter, could I be a carrier?”

“Yes, could he be a carrier?” Olga added.

“Absolutely not,” Dr. Ciletti said. “Let me show you why.”

Questions
. Do autosomal dominant disorders skip generations?
. Could Greg or his mother be carriers of the gene that causes myotonic dystrophy?
. Is there a possibility that Greg’s aunt or uncle is homozygous for the myotonic dystrophy (md) gene?
. Symptoms of myotonic dystrophy sometimes don’t show up until after age fi fty. What is the possibility that

Greg’s cousin has inherited the md gene?
. What is the possibility that Greg and Olga’s children could inherit the md gene?

References
Myotonic Dystrophy Fact Sheet

http://www.mda.org.au/specifi c/mdamyt.html

Human Genetics for First Year Students: Pedigree Construction
http://www.uic.edu/classes/bms/bms655/lesson3.html

http://www.mda.org.au/specific/mdamyt.html

http://www.uic.edu/classes/bms/bms655/lesson3.html

“In Sickness and in Health” by Barry Chess Page 

Part III—Autosomal Recessive Traits
“Well, I certainly feel better about that,” said Greg. “I guess there is no reason to worry about passing on md to our
children. Th ey’ll just have to worry about inheriting their father’s incredible good looks, fabulous sense of humor,
creativity …”

“And modesty … Hold on a second, God’s gift to the world,” Olga chimed in. “We still haven’t talked about factor viii
defi ciency, which is why we came here in the fi rst place.”

“Well,” Dr. Ciletti began, “factor viii defi ciency is what’s known as a sex-linked disease. Before we get to that, let’s take
a look at a disease with a slightly simpler mode of inheritance. Many traits, whether or not they are considered to be
diseases, are described as autosomal recessive traits. Th ese are the ones you alluded to earlier when you talked about
diseases that skip generations and about people being carriers. Some common recessive traits include albinism, sickle
cell disease, and cystic fi brosis, which I promise we will get to, Olga. Now, let’s look at some of the rules governing
these types of traits.”

Questions
. What are the hallmarks of an autosomal recessive trait?
. What does consanguineous mean? Why is this concept especially important when discussing recessive

genetic disorders?
. What is it about the inheritance pattern of factor viii defi ciency seen in Greg and Olga’s pedigree that point

toward it not being an autosomal recessive trait?

References
Autosomal Recessive Inheritance

http://www.uic.edu/classes/bms/bms655/lesson5.html

What is Albinism?
http://www.albinism.org/publications/what_is_albinism.html

Genetic Disease Profi le: Sickle Cell Anemia
http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/sca.shtml

Genetics Home Reference: Cystic fi brosis
http://ghr.nlm.nih.gov/condition=cysticfi brosis

http://www.uic.edu/classes/bms/bms655/lesson5.html

http://www.albinism.org/publications/what_is_albinism.html

http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/sca.shtml

http://ghr.nlm.nih.gov/condition=cysticfibrosis

“In Sickness and in Health” by Barry Chess Page 

Part IV—Sex-Linked Inheritance
“Alright,” Olga began, “so factor viii defi ciency is sex-linked because it only aff ects men. Does it require the presence of
testosterone or something like that?”

“No, but there are many traits that do depend on the presence or absence of sex hormones. We call them sex-infl uenced
traits. Sex-linked traits get their name from the fact that the genes that cause them are carried on the X chromosome,
which is one of the chromosomes responsible for determining what sex a person will become. Let’s take a look at how
factor viii defi ciency runs in both your families.”

Questions
. What are the characteristics of X-linked recessive inheritance?
. Why does a son never inherit his father’s defective X chromosome?
. What is required for a woman to display a sex-linked recessive trait?
. Return to the pedigree drawn earlier for Greg and Olga; mark those persons who are carriers of the factor

viii defi ciency gene.
. What is the chance that Olga carries the gene for factor viii defi ciency? Calculate the probability that she

will pass it to her off spring. Will male children be aff ected in a diff erent way than female children?
. What is the chance that Greg carries the factor viii gene? Can he pass the gene on to his sons? His

daughters? How will each be aff ected?

References
Human Genetics for First Year Students: X-linked Recessive Inheritance

http://www.uic.edu/classes/bms/bms655/lesson7.html

X-linked Inheritance: Red-Green Color Blindness, Hemophilia A
http://www.musckids.com/health_library/genetics/xlink.htm

http://www.uic.edu/classes/bms/bms655/lesson7.html

http://www.musckids.com/health_library/genetics/xlink.htm

“In Sickness and in Health” by Barry Chess Page 

Part V—Population Genetics
“Finally,” Dr. Ciletti began, “let’s talk about cystic fi brosis. Now I mentioned that it is probably not something to worry
about since neither of you has it in your family history, but there is a way to fi gure out the odds of being a carrier even
without a past family history. Remember that in the case of a recessive autosomal disease like cf, for the disease to
show up unexpectedly in your off spring both you and Greg would have to be carriers. We can estimate the probability
of each of you being carriers by looking at the population as a whole.”

“You mean all the people on earth?” Olga asked.

“No. For purposes of genetics you each belong to diff erent populations,” Dr. Ciletti began. “Now Olga, you’re of
European descent, correct?”

“Yes, Swedish and German.”

“And obviously Caucasian. Now I can look up the carrier frequency, that is, the fraction of people in your population
group that carry the most common cystic fi brosis allele. As it happens, one of every twenty-three Caucasians of
European descent carries a recessive allele for cf.”

“Th at doesn’t sound very encouraging,” Olga interjected. “I have a  in  chance of having a child with cystic fi brosis.”

“Not at all. You just have a  in  chance of carrying the cf gene.” Dr. Ciletti replied. “Now Greg is Asian American
and within his population group the carrier frequency is  out of . Making the odds even longer is the fact that
if you are a carrier you have only a - chance of passing on your disease causing allele. So the chance of you two
producing a baby with cf is actually / × / × ½ × ½ or  out of 16,560. So, just how big a family were you
planning to have?”

“But wait,” said Greg. “If a carrier is someone who doesn’t display any of the features of a disease, how can you know
how many carriers are in a population?”

“Good question, Greg. As an old professor of mine once said, ‘It all comes down to minding your P’s and Q’s.’ In a
large population, the carrier frequency can be estimated by looking at the number of persons with the disease and then
doing a little algebra. Th ere are two equations we need to remember. Th e fi rst describes all the alleles in the population
and it just says that P + q = . In other words, of all the alleles in the population, a percentage of them are the healthy
version, which we can call P. So if  of the alleles in a population are healthy, then P must be .. Th e rest of the
alleles must be the disease causing form, or q. If P is ., then q must be ., so that P + q = .

“But how do you know the percentage of q alleles in a population?” asked Olga. “Th e only people you can really
identify are the people with the disease.”

“Exactly, and that brings us to the second equation we need to look at.”

Questions
. What is the second equation?
. Th e incidence of cystic fi brosis in Hispanic Americans is / while in African Americans cystic fi brosis

is seen in  of every , births. What is the carrier frequency for each of these populations?
. What is the probability of two Hispanic Americans having a child with cystic fi brosis, given that there is no

history of the disease in either’s family?
. Carol is an African American woman who does not suffer from cf. Both of her parents are healthy

but her brother has cystic fibrosis. Carol is planning a family with her husband Marcus, who is also
African American but who has no history of cf in his family. What is the probability of their having
a child with cf?

“In Sickness and in Health” by Barry Chess Page 

References
Hardy-Weinberg Equilibrium: Demo problem 

http://science.nhmccd.edu/biol/hwe/q1d.html

Mayo Foundation: Cystic Fibrosis
http://www.mayoclinic.com/health/systic-fi brosis/DS00287

http://science.nhmccd.edu/biol/hwe/q1d.html

http://www.mayoclinic.com/health/systic-fibrosis/DS00287

“In Sickness and in Health” by Barry Chess Page 

Image Credit: Diaper pin photograph copyright © Liz Van Steenburgh.
Copyright ©  by the National Center for Case Study Teaching in Science.
Originally published // at http://www.sciencecases.org/sickness_and_health/sickness_and_health.asp
Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.

Part VI—Unsettled Issues
“So, is it possible to test for each of these diseases?” asked Greg.

“Yes, but for the sake of practicality, or expense, as some would say, we only test for those diseases that are reasonably
likely based on a patient’s history. We wouldn’t for example test either of you for the presence of the cf allele.”

“Wait a minute,” Olga began, “what about a disease that doesn’t show up until later in life. Greg’s uncle didn’t show any
symptoms of myotonic dystrophy until he was something like forty …”

“Forty three,” Greg corrected.

“Yeah, anyway, if a genetic test shows that you are going to get a genetic disease and it becomes part of your medical
history, could an insurance company exclude it as a pre-existing condition, even though you don’t have it yet?”

“Well, the law is actually quite unsettled about the issue. Genetic testing has the power to predict the occurrence, or
at least the likelihood of occurrence, of many diseases—cancer, Alzheimer’s disease, and diabetes just to name a few.
Many people are not comfortable with that information being part of their medical records because they are afraid it
could lead to a loss of insurance, losing out on a job, or some other form of discrimination. But,” Dr. Ciletti said with
fi nality, “that is a subject to take up with lawmakers. It is entirely possible that after the conversation we’ve just had
that you two know far more about the subject of genetic testing than your congressman or senators. If you’re concerned
about the legal ramifi cations of genetic testing, you should let them know. It was a pleasure meeting both of you.”

“Likewise, Doctor. You really helped to put my mind at ease,” Olga said.

“Yeah, I think we both feel a lot better, thanks,” said Greg.

Questions
. What are some of the risks and benefi ts of genetic testing as it relates to legal (not medical) issues?
. Do you think an unintended consequence of genetic testing could be that people would be less liable to

seek medical care out of fear that they could later be denied life or health insurance? What laws should be
used to govern the use of genetic data of this type?

References
Mayo Foundation: Genetic Testing

http://www.mayoclinic.com/health/genetic-testing/FL00076

Private Medical Information Isn’t So Private
http://www.bankrate.com/brm/news/pf/20050830a1.asp

National Society of Genetic Counselors
http://www.nsgc.org/newsroom/NSGC_SACGHS_October_2004

http://www.mayoclinic.com/health/genetic-testing/FL00076

http://www.bankrate.com/brm/news/pf/20050830a1.asp

http://www.nsgc.org/newsroom/NSGC_SACGHS_October_2004

http://www.sciencecases.org/sickness_and_health/sickness_and_health.asp

http://ublib.buffalo.edu/libraries/projects/cases/case.html

http://ublib.buffalo.edu/libraries/projects/cases/guidelines.html