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Genetic Disorder Activity Stations
Overall Expectations: D1 Students will evaluate the importance of some recent
contributions to our knowledge of genetic processes, and analyze social and
ethical implication of genetic and genomic research.
D2 Students will investigate genetic processes, including those that occur during
meiosis, and analyze data to solve basic genetics problems involving monohybrid
and dihybrid crosses.
Students will spend approximately 15-20 minutes per station. Students are to
discuss all aspects of each genetic situation with their respective group
Station A)
Build a Pedigree:
Woody Guthrie was a renowned folk singer, most popular today for the song,
"This Land Is Your Land." He died in 1967 from Huntington disease. Read the
biography provided and create a pedigree of his life.
(1) What is the probability Arlo could inherit Huntington Disease?
(2) If Arlo does not get Huntington Disease, will any of his children?
(3) If neither parent has Huntington Disease, what is the probability you will get
the disease?
Station B)
What would you advise?
Read the scenario and answer the question based on your thoughts. When
finished discuss your response with your group. Each person in the group should
share their response. Once you have verbally discussed, you may edit your
response. Include the changes you have made and what caused you to make
each change.
Janice is 39 years old and has three children. Her mother died from Huntington
Disease at the age of 61. Janice never wanted to undergo any form of testing.
She pretended HD didn't exist. This was her coping mechanism. She had always
wanted children and felt that if she found out she had Huntington Disease she
would never be comfortable knowing she could be passing the disease on to her
children. She has lived her life ignoring the issue. Now, however, she is can
hardly stand not knowing. Every day she wonders if this will be the day she starts
having symptoms. Every time she has a slight muscle spasm she wonders if this
is the beginning of the long decline. The uneasiness has caused her to
contemplate suicide. In many ways she wishes she had the courage to undergo
the test for heterozygosity because if it came back negative she could finally rid
herself of all her fears; however, if the test were to come back positive she is not
sure she could go on knowing that inevitably she would die such a tragic death.
Even worse would be the guilt she would feel knowing that since she has
Huntington disease, each of her children now has a 50% chance of also being
affected. What would you, Janice's counselor, recommend?
Station C) Hemophilia: “The Royal Disease”
Yelena Aronova-Tiuntseva and Clyde Freeman Herreid
University at
Buffalo, State University of New York
Hemophilia is an X-linked recessive disorder characterized by the inability to
properly form blood clots. Until recently, hemophilia was untreatable, and only a
few hemophiliacs survived to reproductive age because any small cut or internal
hemorrhaging after even a minor bruise were fatal. Now hemophilia is treated
with blood transfusions and infusions of a blood derived substance known as
anti-hemophilic factor. However, such treatment is very expensive and involves
the risk of contracting AIDS.
Hemophilia affects males much more frequently (1 in 10,000) than females (1 in
100,000,000). This occurs because a critical blood clotting gene is carried on the
X chromosome. Since males only carry one X chromosome, if that is defective,
hemophilia will immediately show up. An early death is likely. Females, on the
other hand, carry two X chromosomes. If only one is defective, the other normal
X chromosome can compensate. The woman will have normal blood clotting; she
will simply be a carrier of the recessive defective gene. This fact will be
discovered if some of her children are hemophiliacs. Naturally, women
hemophiliacs are rare because it takes two defective X chromosomes in order for
the condition to be seen.
Hemophilia has played an important role in Europe’s history, for it suddenly
cropped up in the children of Great Britain’s Queen Victoria. It became known as
the “Royal disease” because it spread to the royal families of Europe through
Victoria’s descendants. Queen Victoria had always been worried about the
quality of the blood of the British royal family. Her feelings about the necessity of
revitalizing what she called the “lymphatic” blood of their houses are reflected in
her letter to her daughter Vicky: “I do wish one could find some more black eyed
Princes and Princesses for our children! I can’t help thinking what dear Papa
said—that it was in fact when there was some little imperfection in the pure Royal
descent that some fresh blood was infused… For that constant fair hair and blue
eyes makes the blood so lymphatic… it is not as trivial as you may think, for
darling Papa—often with vehemence said: ‘We must have some strong blood.’”
It is doubtful that at the time of writing this letter, the Queen knew exactly what
was wrong with her family’s blood. Hemophilia first appeared in Victoria’s family
in her eighth child, Prince Leopold, Duke of Albany. Throughout his short life,
Leopold had suffered severe hemorrhages, and always was described as “very
delicate.” Leading the life of a normal youngster was impossible for Leopold
because any cut or bump could lead to death and it was necessary to keep him
always under strict surveillance. However, in spite of all the protection, Prince
Leopold died at the age of thirty-one as the result of a minor fall.
The appearance of hemophilia in one of Victoria’s sons upset and confused the
Queen, who could only protest that the disease did not originate in her side of the
family. Yet, a whisper about the “curse of the Coburgs” was spread about. This
curse was supposed to have dated from the early nineteenth century, when a
Coburg prince had married a Hungarian princess named Antoinette de Kohary. A
monk, a member of the Kohary family, envied the wealth inherited by the happy
couple from the bride’s father, and cursed future generations of Coburgs with the
disease. Of course, hemophilia affecting Victoria’s offspring had nothing to do
with the curse. The traditional view is that there was a mutation in either her or in
a sperm of her father, Edward Augustus, Duke of Kent. From there it spread
through the Royal Houses of Europe as monarchs arranged marriages to
consolidate political alliances. We can trace the appearance of hemophilia as it
popped up in Spain, Russia, and Prussia by looking at the family tree.
Answer the questions below:
1) First, let’s take a look at Queen Victoria’s son Leopold’s family. His daughter,
Alice of Athlone, had one hemophilic son (Rupert) and two other children—a boy
and a girl—whose status is unknown. a) What is the probability that her other son
was hemophilic? b) What is the probability that her daughter was a carrier?
Hemophilic? c) What is the probability that both children were normal?
Fortunately, Leopold was the only one of Victoria’s sons who suffered from
hemophilia. Her other three sons, Edward, Alfred, and Arthur, were unaffected.
Since the present royal family of England descended from Edward VII, the first
son, it is free from hemophilia.
Louise, Queen Victoria’s fourth daughter and sixth child, did not have children
and her status as a carrier cannot be assessed. Vicky, the first child, and Helena,
the fifth child, had children, none of whom was hemophilic, indicating that the
mothers probably were not carriers.
2. Now for the Spanish connection: Victoria’s youngest child, Beatrice, gave birth
to one daughter, one normal son, and two hemophilic sons. Looking at the
pedigree of the royal family, identify which of Beatrice’s children received the
hemophilic gene; why can you make this conclusion? Notice that Beatrice’s
daughter, Eugenie, married King Alfonso XIII of Spain and had six children, one
of whom was the father of Juan Carlos, the current King of Spain. Would you
predict that Juan Carlos was normal,
a carrier, or a
Queen Victoria’s third child, Alice, passed hemophilia to the German and
Russian imperial families. Of Alice’s six children, three were afflicted with
hemophilia. At the age of three, her son Frederick bled for three agonizing days
from a cut on the ear. Eventually, the flow of blood was stanched. But a few
months later, while playing boisterously in his mother’s room, the boy charged
headlong through an open window and fell to the terrace below. By the evening
he was dead from the internal bleeding.
Alice’s daughter Irene, a carrier, married her first cousin, Prince Henry of Prussia,
and gave birth to two hemophilic sons. Every attempt was made to conceal the
fact that the dreaded disease had shown itself in the German imperial family, but,
at the age of four, Waldemar, the youngest of the princes, bled to death. The
other prince, Henry, died at the age of fifty-six.
Alice’s other daughter, Alix, was also a carrier. Had she accepted the offer of
marriage from Prince Eddy, or his brother George, hemophilia would have been
re-introduced into the reigning branch of the British royal family. But Alexandra
(Alix) married Tsar Nikolas II instead and carried the disease into the Russian
imperial family. She had four daughters, Olga, Tatiana, Marie, and Anastasia,
before giving birth to the long-awaited son, Alexis, heir to the Russian throne.
These children, along with their parents, were eventually murdered during the
Russian Revolution.
Within a few months of his birth, his parents realized that their precious and only
son, Alexis, had hemophilia. The first sign had been some unexpected bleeding
from the navel, which had stopped after a few days. Much more serious,
however, were the dark swellings that appeared each time the child bumped an
arm or a leg. And worst of all was the bleeding into the joints. This meant a
crippling of the affected limbs in addition to excruciating pain. As the boy grew
older, he was obliged to spend weeks in bed, and after he was up, to wear a
heavy iron brace.
Neither well-experienced doctors nor numerous prayers to God by desperate
parents seemed to help the suffering child. Distressed over their son’s condition,
his parents, the Tsar and Tsarina, turned to the monk Rasputin, a spiritualist who
claimed he could help Alexis. Rasputin received an unlimited trust from
Alexandra because he was the only person who was able to relieve her son’s
sufferings. How he managed to do this is uncertain. “A likely explanation is that
Rasputin, with his hypnotic eyes and his self-confident presence, was able to
create the aura of tranquillity necessary to slow the flow of blood through the
boys veins. Where the demented mother and the dithering doctors merely
increased the tenseness of the atmosphere around the suffering child, Rasputin
calmed him and sent him to sleep.” While Tsar and Tsarina were preoccupied
with the health of their son, the affairs of state deteriorated, culminating in the
Russian revolution.
Alexis did not die from hemophilia. At the age of fourteen he was executed with
the rest of the family. His four oldest sisters were also young and didn’t have
children, so we don’t know whether any of them was a carrier. But we can make
an estimate. a) What are the probabilities that all four of the girls were carriers of
the allele hemophilia? b) Supposing Alexis had lived and married a normal
woman, what are the chances that his daughter would be a hemophiliac? c)
What are the chances his daughters would be carriers? d) What are the chances
that his sons would be hemophiliacs?
4. In 1995, a sixty-three year old man named Eugene Romanov, a resident of the
former Soviet Union, turned up. He shared both the disease and his last name
with the royal family of czarist Russia. He proclaimed himself a grandson of
Nikolas II’s youngest daughter, Anastasia, whose body had never been
recovered, and who was believed by some to have managed to survive the
revolution. Eugene Romanov claimed Anastasia was raised by a farmer, and
later she married a nephew of her adopted parents and had a daughter,
Eugene’s mother. a) According to Eugene’s argument, what was the likely
hemophilic status of Eugene’s mother and grandmother? What about his father
and grandfather? Is this argument plausible? b) How plausible is it that Eugene
inherited both hemophilia and the last name from the royal family? (Hint: Look
how each of them is passed from generation to generation.)
Prince Charles is the designated next king of England. His well publicized
marriage to Princess Diana produced two sons before it ended in an acrimonious
divorce. If you learned that one of the two was a hemophiliac, what are the
possible explanations for this event?
5. Finally, our speculative natures compel us to mention that in 1995 two British
brothers produced a new book (Queen Victoria’s Gene) with a breathtaking
suggestion. Professors Malcom Potts, an embryologist at Berkeley, and William
Potts, a zoologist at Britain’s Lancaster University, suggest that Queen Victoria
might have been illegitimate. They point out that neither her father nor her
husband was a hemophiliac. So either there was a spontaneous mutation—a
one-in-50,000 chance—or Victoria is the daughter of someone other than the
Duke of Kent. Think of the possible consequences to European history: no
Victoria, and the current Prince of Hanover, Ernst (descendent of the brother of
Victoria’s father), would be King of England today. More importantly, no Victoria
would mean no hemophilic son of the Czar of Russia, no Rasputin, and no
revolution? What are the chances of this scenario?
Station D)
Tay Sachs Disease
Tay Sachs is autosomal recessive and typically occurs more in the Ashkenazi
Jew population. There is a 1/30 chance of being a carrier. The disorder is
degenerative causing death usually by age 5. Testing is available to identify
carriers, as well as detect genotypes while prenatal.
Elise Catherine ten Berge was born on February 5, 2003. She was our first child
and as all new parents do, we thought about what Elise’s future would be like:
her first word, her first step, and her first day of school. Little did we know that
Elise had a degenerative disease called Tay-Sachs, which was already ravaging
her central nervous system. Elise would never have a first word, first step or first
day of school.
Elise appeared completely normal at birth and reached the developmental
milestones she should have for the first few months of her life. At nine months
old, she was able to roll over onto her stomach and hold toys, but she was not
able to sit up. At first, Elise's pediatrician told us "not to worry" because all babies
reach their milestones at different times.
Even though the doctor said not to worry, we were worried. When Elise was
almost 10 months old, she was evaluated be an Occupational Therapist. This
evaluation led to an appointment with a pediatric neurologist. An MRI revealed
some abnormalities in her brain, which indicated that she could have some type
of metabolic disorder. Blood/urine tests and a muscle biopsy did not produce a
further diagnosis.
By the time Elise was 13 months old, despite physical and occupational therapy,
her fine and gross motor skills had regressed to the point where she could no
longer roll over or hold toys. Her startle response to noises worsened. At the
time, we were unaware that the startle response Elise was exhibiting was a
classic characteristic of a child with Tay-Sachs.
We thought we would finally get to the bottom of all this
A new pediatrician suggested that we take Elise to have her eyes checked
because "some metabolic diseases can be diagnosed that way." At the end of
March 2004, an opthamologist dilated Elise's pupils and found cherry red spots.
We thought this was great news - we would finally be getting to the bottom of all
this. We were hoping that this information would lead us to a diagnosis, which
meant we could start treating Elise and help her get better. We had no idea that
cherry red spots were the worst possible thing the eye doctor could have found.
On April 15, 2004, when Elise was 14 months old, we took her to a pediatric
neurologist in New York City. After reviewing Elise's records, the first question
the doctor had was about our heritage. I knew where he was leading with that
question because I had done some internet searches on cherry red spots.
Everything I read was leading in the same direction - infantile Tay-Sachs
disease. The only piece that didn't fit with everything I read was that Ashkenazi
Jews were high carriers of the Tay-Sachs' gene. When I told the doctor that we
weren't Jewish, I will never forget how he said, "It doesn't matter." A blood test
confirmed that Elise had infantile Tay-Sachs disease.
The doctor informed us that most children with Tay-Sachs don't live past the age
of 3. We were told that Elise was going to go blind, deaf, have seizures, need a
feeding tube for nourishment, lose all mobility and become unaware of her
surroundings. To make matters worse, I was already 28 weeks pregnant with our
second child. There was a 1 in 4 chance that the baby I was carrying would also
have Tay-Sachs disease. At 30 weeks pregnant, I had an amniocentisis which
thankfully predicted that the fetus was unaffected. When Elise’s little sister,
Caroline, was born in July 2004, we had her cord blood tested which reaffirmed
that she did not have Tay-Sachs disease.
Elise started having seizures when she was about 18 months old and she had
her feeding tube placed when she was 20 months old. Elise can no longer see,
she doesn't giggle (except during giggle seizures), smile, or cry anymore and she
sleeps most of the time. Elise suffers from chronic respiratory issues and has
been hospitalized for pneumonia and RSV. She requires 24 hour care and is
under constant monitoring. She does still respond with a mad face to things she
doesn't like (brushing her teeth, changing clothes, deep nasal suctioning). She
also responds with little coos and sighs to let us know that she is okay, and we
love those.
We have chosen to celebrate Elise’s life
Instead of focusing on all of the things that Tay-Sachs has taken away from
Elise, we have chosen to celebrate Elise’s life. No matter how short her life will
be, we have witnessed that it has been a life of value and meaning. In the end,
Elise’s life will be measured by memories, not by years. She has taught us
numerous things, most importantly, that life is precious. We have learned the
wisdom of a lifetime from Elise in just a few years. For that, we are forever
If love was the cure, Elise would live forever.
Tay Sachs is a very sad disease. A child born perfectly healthy suddenly begins
to lose all muscle control and degenerate. The only way to eradicate this disease
and other autosomal recessive diseases is through testing for it and then
preventing two carriers from both passing on the defective gene. The ethics
behind such action can be brought into question.
(1) Should all individuals be forced to be tested and those who are carriers be
notified? Why or why not? Should only individuals in high risk populations be
tested? Why or why not?
(2) Should all pregnant women be tested for Tay sachs? Should pregnant women
in high-risk populations be tested for Tay Sachs? Defend your answer.
(3) What would one counsel an individual who discovered he or she was a
(4) Should the government provide funding for couples who are both carriers of
Tay-Sachs to undergo in vitro fertilization, test the single-celled embryos and
then implant only those without the disease?
Station E)
Monica and Sami have two adopted children aged nine and seven. Now, at the
age of 38, Monica is pregnant for the first time and the whole family are
Monica's doctor is suggesting that as she is 38 years old, she should have a test
called amniocentesis (pronounced am-nee~yo-sen-tea-sis) when she is about 16
weeks pregnant.
Amniocentesis involves drawing out a small amount of the fluid which surrounds
the fetus and examining cells in this fluid. The test can accurately predict if the
fetus is affected by Down's Syndrome. Monica is being offered this test because
older mothers (aged 35 and over) have a greater chance of having a baby with
Down's Syndrome. A few women (about 1 in every 100) will lose their unborn
baby through miscarriage because of the test.
Monica is worried about the test. This pregnancy is very precious to both Monica
and Sami as Monica was told years ago that she was infertile and would never
be able to have a baby.
Visit the following website and read more about the history of Down Syndrome.
1. Do you think Monica should have the test?
2. What do you think Monica and Sami should do if the test shows that their
unborn baby has Down's Syndrome?
3. Do you think it is important that women are allowed to choose whether or
not to terminate an affected pregnancy, or do you think that abortion is
always wrong?
4. Some people say that aborting a fetus on the grounds of disability is a
form of discrimination against disabled people. What do you think?