Module 1: Genetics, Ethics, and Society - CISAT Sharepoint

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Oct 23, 2013 (3 years and 10 months ago)

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Chapter 2


Problem
-
Based Learning Modules









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12







2.1 Module 1:

Genetics, Ethics, and Society




Objective



This module serves as a supplement to a unit on biotechnology and
genetics. Specifically, the case studies and ensuing discussion questio
ns provide
each student with a real application of biotechnology and genetics as it applies to
everyday lives. Given this situation, each student is encouraged to temporarily
place him/herself in the realm of each vignette and ultimately emerges
knowledge
able of the following: the disease beta thalassemia major; how to
construct a pedigree; terminology in genetics; structure and function of
hemoglobin; typical treatments for blood
-
based disease states, and ethical
guidelines for human genetics (and how to

apply these guidelines to specific
situations).



Virginia State Standards of Learning


The following is the Virginia State SOL that applies to this module:




BIO 6.
The student will investigate and understand common mechanisms
of inheritance and protein s
ynthesis. Key concepts include

o

Cell division;

o

Sex cell formation;

o

Cell specialization;

o

prediction of inheritance of traits based on the laws of heredity;

o

effects of genetic recombination and mutation;

o

events involved in the construction of proteins; and

o

e
xploration of the impact of DNA technologies.


(Source:
www.pen.k12.va.us/VDOE/SOLcommentforms/scisolcurrfrmwrkcmnts.html
.)





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Testing of Module



An audience of appr
oximately 10 college
-
age students partook in this
module. Although the students have a relatively small background of
biotechnology and genetics, they were still able to provide insight when exposed
to each vignette and ultimately emerged more knowledgeab
le of the objectives of
this lesson.











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Module 1:

Genetics, Ethics, and Society















Invisible Barriers:


Case Studies of a High School

Athlete and a Newborn With

Severe Anemia







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Invisible Barriers:

Case Studies of a
High School Athlete and a Newborn
With Severe Anemia


























































































































Jenny Bower is a
talented high school
athlete. Competing in
sports such as cross
-
country, volleyball, and
outdoor track, she is in
incredible physical
condition.


During the fall
months she competes on
her cross
-
country team,
which is second
in the state
of New Jersey. Together
with the other top
members of the team,
Jenny wins races and
always pulls through in
critical competitions.
However, during practice,
her breathing becomes
shallow and labored at
times. Also, of the seven
top members

of the team
who always practice
together, only Jenny has
failed to improve on her
race times throughout the
season.










In practices, I
always train up
front with the top
runners, but during
the races, my
breathing always
becomes
labored…and up
until now, I had no
idea why!”

Together with her
coach, Jenny consults her
physician, who extracts and
analyzes a sample of her
blood.


A few weeks later,

Jenny receives the news that
she is a carrier of the
recessive trait for beta (


th慬慳semi愮a⁔his⁨eredit慲y
dise慳e m慮ifests itself⁩n
慮yf⁴he hundreds of
mut慴ions⁷ithin⁴he⁢et愠
globin genef⁴he
hemoglobin molecule (愠
componentf⁲ed⁢lood
c
ells)⸠⁃慲riers of⁴his⁧enetic
tr慩tften eperience minor
symptoms of⁴he leth慬 bet愠
th慬慳semi愠m慪or⸠⁉n this
case, Jenny’s red blood cells
doot⁣ont慩n⁴heorm慬
慭ountfxygenⰠIhich
le慤s to⁨er慢ored
bre慴hing⁤uring
competition⸠†




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If you were Jenny, what three questions would you ask your doctor?













































































































Knowing that this is a genetic condition, if you were Jenny, what questions
would you ask your mother about her family history of this disease?

































































































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An Interview with Jenny’s Mother











































“I remember back a few years when Jenny had first started running cross
country. She started

off her freshman season extremely well, and then as the
next three seasons progressed, Jenny reached a plateau and never seemed to
improve her physical condition. Despite all the hard work and training during
practices, Jenny was never able to run much f
aster than she had her first season
on the team. I remember how Jenny would come home from races and practices
in a state of disappointment and frustration. It wasn’t until her physical during
her senior year that Jenny finally found out she was a carrie
r of beta thalassemia
and expressed some of the symptoms of the disease.


“I come from a family with a strong Italian background. My father is
100% Italian, and his grandparents emigrated from Italy some time ago. My
father’s family has a strong Mediterr
anean anemia ancestry, which explains why
I have a slight form of iron
-
deficiency anemia. I inherited the allele from my
father, who inherited the recessive trait from his father. Along with myself, my
four siblings (one sister and two brothers) are also

carriers of beta thalassemia
and have even passed on the mutation to some of their children. None of my
siblings has the major form of this disease. This trait is not present in any of my
mother’s family.



“It wasn’t until Jenny’s physical her senior y
ear of high school that I
determined that she also is a carrier of this condition and she runs the risk of
someday passing it on to her children. Jenny has one sister and one brother.
Neither shows signs of anemia.


“Jenny’s physician says that if Jen
ny marries and has children with a man
who is also a carrier of this trait, she has a 25% chance of having a child who
receives two bad copies of the allele; the baby will most likely not survive more
than a few months. Hopefully Jenny’s children will not

have to experience the
mild symptoms that carriers of the beta thalassemia trait often express. “











































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Construct Jenny’s Pedigree Below










































(A
pedigree

traces the patterns of inher
itance of genetic traits from generation to
generation.)





































What is Jenny’s
genotype

(the genetic constitution or composition of an individual)?




What is Jenny’s
phenotype

(the observed result of the interaction of the ge
notype with
environmental factors
-
the observable expression of a particular gene or genes)?







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Biochemical and Ethical Analysis of Beta Thalassemia
-
A Situational Vignette




























What follows is an excerpt of a case study concerning a

real couple’s
firstborn child. The web site entitled
Case Studies in Science

from the State
University of Buffalo contains a series of case studies related to all areas and
types of science. Specifically, this is an excerpt of the case study for Cooley
’s
anemia (beta thalassemia major) written by Christopher T. Bailey (of the
Department of Biological and Chemical Sciences at Wells College) and
Mohammad Mahroof
-
Tahir (of the Department of Chemistry at St. Cloud State
University). The full case study can

be found at
www.sciencecases.org/cooley/cooley.asp
.










“Max and Andrea Foresti are sitting in the waiting room of their family
physician, Dr. Mary Litton.


A young couple, Max and An
drea have been
married just two years and have a son, Peter, whom they are bringing in for a
follow
-
up visit with the doctor.


They are concerned because Peter has recently
been suffering from a number of infections.


Although Peter seemed to be a happy
an
d healthy newborn, he has grown increasingly listless over the past few
months.


He has lost much of his appetite and his complexion has become pale.


Max and Andrea believe that Peter has become anemic due to his poor diet; both
Andrea and Max themselves
suffered from jaundice as babies.


“The family is called in to see Dr. Litton, who, after exchanging pleasantries,
reviews Peter's symptoms with them and then says, ‘You'll remember that when
you were last here I ordered some blood work to be done on Peter
.


The results of
the blood work have confirmed a suspicion I had based on Peter's symptoms and
some other things you told me.


Peter is suffering from thalassemia.’


“Max interrupts Dr. Litton.


‘What is thalassemia?


I've never heard of that
before.’




‘Well, thalassemia is a genetic blood disorder.


In fact, it was your telling me
during your last visit that your grandparents had emigrated from Italy that made
me suspect thalassemia.


Thalassemia tends to affect people of Mediterranean
descent.’


“Andre
a, who has grown quite pale, asks anxiously, ‘What is this thalassemia
doing to Peter?’




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“’Thalassemia causes hemoglobin, the protein in your body that binds and
transports oxygen, to be malformed.’


This case continues with a description of symptoms, trea
tment options,
and life expectancy for a patient like Peter. The authors of this case study ask
students to put themselves in the role of one of Peter’s parents. The students
need to choose an appropriate treatment for Peter. However, they need to
inves
tigate the disease further before they can make an informed decision.


These are some of the questions the case study suggests for the students to
investigate:


(Note

students may consult the Internet, magazines, books, etc. to answer the following
quest
ions.)


1.

What is the basic structure and function of hemoglobin?







2.

Which proteins transport and store iron in the body?







3.

What is thalassemia and what are its causes?







4.

What are the different types of thalassemia?








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5.

What are the symptoms of
beta thalassemia major (Cooley's anemia)? Why don't
these symptoms appear at birth?







6.

What are the current treatments for thalassemia?


What are their problems?







7.

What is iron overload?


What are its causes?







8.

What are chelators?







9.

What is

chelation therapy and why is this treatment necessary to combat iron
-
overload?







10.

What should Peter's parents do?



































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Teacher Reference (Example of Possible Answers to Discussion Questions)




If you were Jenny, what three

questions would you ask your doctor?


1.

What is beta thalassemia in general? What cells and/or tissues in the
body does it alter?

2.

Why am I a carrier? Is there a geographical prevalence of the disease?

3.

Will my children also be carriers of the disease?


Kno
wing that this is a genetic condition, if you were Jenny, what questions
would you ask your mother about her family history of this disease?


1.

Which one of your parents is a carrier of the disease?

2.

Do my siblings have the trait?

3.

Where did your ancestors com
e from?

4.

Is Dad also a carrier of the disease?

5.

How did the doctor determine that I am a carrier of beta thalassemia?

6.

What types of symptoms do you experience?


Construct Jenny’s Pedigree


A pedigree is a chart that traces the family history of a particula
r genetic
trait.


(
www.sh.lsuhsc.edu/pediatrics/genetics/conf%201%20key%2099.htm

[
Medical Genetics
211
] is a great web site to educate students on the construction of ped
igrees
based upon information provided; this web site also provides several vignettes
where the students can predict the pedigree and then check their predictions
against answers provided.)




Jenny is a carrier of the beta thalassemia trait; her brother and

sister are
not.



Jenny’s mom is also a carrier of the trait, whereas her father is not.



Jenny’s grandfather on her mother’s side is a carrier of the disease, but her
grandmother is not.



All of Jenny’s mother’s siblings are carriers, but not one of them act
ually
has the expresses the recessive condition of beta thalassemia.



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Pedigree:



Generation


I










II












III



(In this pedigree, the * refers to Jenny.)


Legend:


Unaffected female (circle) and male (square)


Heterozygous female (cir
cle) and male (square)


Homozygous affected female (circle) and male (square)

there

are no homozygous affected individuals in Jenny’s family.







1

2

3

4

5

6

7

8

9

*10

11



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What is Jenny’s genotype?


Jenny’s genotype for beta thalassemia is


0
. The Punnett Square below,
Figu
re 1
, found on the web site
Thalassemia.com
, illustrates this (note that the
superscripted “0” refers to the allele Jenny inherited from her mother, who is a
carrier of the disease). Judging by this square, Jenny’s parents had an overall
50% chance of pas
sing on the beta thalassemia trait to each of their children (in
this square, the father is also heterozygous for the beta thalassemia trait, which is
untrue of Jenny’s father).




What is Jenny’s phenotype?


Due to the fact that Jenny is only a carrier of the beta thalassemia trait, she
expresses only mild symptoms. Jenny’s troubled breathing during cross
-
country
practices is a direct result of the manifestation of mild sympt
oms of beta
thalassemia. A person with beta thalassemia major (Cooley’s anemia) would
have much more serious symptoms.


Biochemical and Ethical Analysis of Beta Thalassemia
-
A Situational Vignette


Following are one set of possible answers and explanat
ions for the ten
discussion questions provided. Keep in mind that there are many correct
answers to the questions pertaining to the ethical aspects of biotechnology.


1.

What is the basic structure and function of hemoglobin?


Hemoglobin is an abundant prote
in found in red blood cells within the
bloodstream.
Figure 2

shows that normal hemoglobin is a round or ball
-
shaped folded molecule composed of four protein subunits, including two


chains and two


chains (
www.isat.jmu.edu/users/klevicca/sickle_cell
,
September 9, 2002). Each molecule of hemoglobin can carry up to four
molecules of oxygen and delivers oxygen from the lungs to the tissues of
Figure 1.
A Punnett Square of the cross breeding of a mother
and a father who are both heteroz
ygous for the beta
thalassemia trait. (Source:
Thalassemia.com.
http://www.thalassemia.com/medical/beta.shtml
,

March 1, 2003.)



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the body. Hemoglobin then carries the carbon d
ioxide from the body
tissues back to the lungs, so it essentially serves as a transporter of
necessary atoms throughout the body. Hemoglobin needs to be able to
bind oxygen tightly in order to carry out its function, so it is also able to
change its struc
ture in certain situations. Overall, the structure of each of
the globin chains within the hemoglobin molecule is essential to the
function of hemoglobin within the body, and any alteration to the
components of this molecule can cause a number of health c
onsequences.





2.

Which proteins transport and store iron in the body?


Ferritin and transferrin are proteins that store iron and transport it
through the blood according

to Greg Crowther on the web site entitled,
Pumping Iron Into Your Body

(
www.ups.edu/faculty/gcrowther/Misc/RBC/iron.shtml
, March 29, 2003).


3.

What is thalassemia and what are its cau
ses?


Beta thalassemia is one of a group of inherited blood disorders known as
thalassemias. This disorder manifests itself when beta globin, a critical
blood protein, is missing from the oxygen
-
carrying red blood cells. Beta
globin is needed to make hem
oglobin; the beta globin carries the heme
group that binds the oxygen molecules. When the beta globins are not
made, the alpha globins accumulate inside new red blood cells, causing
clumping. There is nothing for the alpha globins to bind with, so no
hem
oglobin is made. The red blood cells then die off, which in turn
causes severe anemia. Beta thalassemia is recessive; a person must inherit
two copies of a mutated beta globin gene to develop symptoms, according
to the web site entitled,
Your Genes Your
Health
-
Beta Thalassemia

(
www.yourgenesyourhealth.org/ygyh/mason/ygyh.html?syndrome=thal
, January
20, 2003).


Figure 2.

The structure of a hemoglobin molecule with two


ch
ains and two


chains. (Source:
www.isat.jmu.edu/users/klevicca/sickle_cell
, September 9, 2002).



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4.

What are the different types of thalassemia?


There are se
veral variants of thalassemia. Alpha and beta thalassemias
are characterized by the lack of


and


globins, respectively, in the
oxygen
-
carrying red blood cells. Other types of thalassemia include beta
thalassemia major (also known as Cooley’s anemia),
thalassemia
intermedia, and thalassemia minor (trait). These types of thalassemias
differ based upon the severity of anemia experienced by the affected
individual. Beta thalassemia major is characterized by severe anemia and
requires constant blood trans
fusions to supply the affected individual
with fresh red blood cells. Thalassemia intermedia is characterized by a
decrease in beta globin production, but the affected individual does not
require chronic transfusion therapy. A mild form of Cooley’s anemi
a also
characterizes thalassemia intermedia. Thalassemia trait occurs in those
individuals who are heterozygous for the recessive beta thalassemia.
Often these individuals experience no symptoms at all, but some may
develop extremely mild forms of anemia

in which the red blood cells are
smaller than normal; this type of mild anemia may also occur during
menstruation or pregnancy.


Figures 3
,
4
, and
5
illustrate normal red blood cells, red blood cells of an
individual affected by alpha thalassemia, and red

blood cells of an
individual affected by beta thalassemia, respectively. Take note of the
major differences of each of the red blood cells in these figures.







Figure 3.

Normal red blood cells. (Source: Ferguson,
Dr. Nancy.
An Overview of Thalass
emia for Parents
Adopting Internationally
.
www.comeunity.com/adoption/health/thalessemia.html
,
April 2, 2003).


Figure 4.

Red blood cells of an individual affected by
alpha thal
assemia. (Source:
www.comeunity.com/adoption/health/thalessemia.html
,
April 2, 2003).



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5.

What are the symptoms of beta thalassemia major (Cooley's anemia)? Why
don't
these symptoms appear at birth?


Beta thalassemia major (Cooley’s anemia) is the most severe thalassemia.
According to Dr. Nancy Ferguson on the web page entitled
An Overview of
Thalassemia for Parents Adopting Internationally
, “infants with thalass
emia
major appear healthy at birth, but develop symptoms around 8 to 10
months of age. These children appear pale, weak, fussy, and have poor
appetites. Their growth is slow and they often become jaundiced [yellow
skin]” (
www.comeunity.com/adoption/health/thalessemia.html
, April 2, 2003).


At the fetal stage, an embryo synthesizes fetal hemoglobin. This fetal
hemoglobin slowly starts being replaced by adult hemoglobin through
gest
ation, but there is still some fetal hemoglobin there when the baby is
born. The beta thalassemia major mutation doesn't kick in until all the
hemoglobin is in the adult form, which can occur a few months following
birth.


6.

What are the current treatments
for thalassemia?


What are their problems?


The most common current treatments for thalassemia include chronic
blood transfusions (hyper transfusions) every three to four weeks,
antibiotic administration, and daily chelation (drug) therapy. Chronic
blood
transfusions cause the build
-
up of too much iron in the blood,
which can lead to excessive heart and liver damage. Patients receiving
hyper transfusions must also take a chelator, which is a drug that binds,
dissolves, and eliminates excess iron. In addi
tion to blood transfusion and
chelation therapy, bone marrow transplant is also a form of treatment for
thalassemia. Bone marrow transplant is extremely risky. Other forms of
treatment still in the research stage are other chelation drug therapies and

Figure 5.

Red blood cells of an individual affected by beta
thalassemia. (Source:
www.comeunity.com/adoption/health/thalessemia.html
, April 2,
2003).



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ge
ne therapy (
www.comeunity.com/adoption/health/thalessemia.html
, April 2,
2003).


7.

What is iron overload?


What are its causes?


Iron overload occurs when iron builds up and collects
into storage in the
blood, rather than becoming integrated into hemoglobin. In terms of
patients with beta thalassemia, chronic blood transfusions can cause iron
overload. Iron is not excreted, but rather stored, so the overload of new
iron via blood tra
nsfusion can cause the storage of excess iron.


8.

What are chelators?


Chelators are small molecules that can bind excess iron and make it
soluble.


The chelated iron is immediately excreted from the body.


9.

What is chelation therapy and why is this treatment

necessary to combat iron
overload?


Patients with beta thalassemia major who undergo frequent blood
transfusions take a type of drug called a chelator, which binds excess iron
in the blood and dissolves it. With chronic blood transfusions, iron build
-
up
within the patient becomes problematic and can cause serious harm to
organs. Therefore, patients must undergo chelation therapy to directly
combat iron overload.


10.

What should Peter's parents do?


This question has no single correct answer. Given the info
rmation
presented by Peter’s physician, there are no easy choices for Peter’s
parents to make. This question is subject to much ethical debate, so
students may refer to the
Ethical Guidelines for Human Genetics from the

World Health Organization

(
www.who.int/ncd/hgn/hgnethic.htm
) found within
Appendix 2

to better make a decision on the actions that Peter’s parents
should take.


To make a distinction concerning the ethical dimension of this vignette,
ethical issues deal with what is moral or right. Legal issues address laws
or regulations that may be set up to protect society members, and social
issues look at how society and its individuals will be affected by certain
decisions.