INTERDISCIPLINARY MATH AND BIOLOGY MODULE: SICKLE CELL
By; REBECCA LANGOMES, FE ARENASA, JULITA BELCHES, JUDITH B. ABERGOS
I. CONTEXT
The purpose of this module is to provide a design of instruction- a framework in which the student plays a role
within a simulation, acquiring knowledge and skills in the process of pursuing a meaningful lesson of sickle cell
wherein there will be interdisciplinary concepts of mathematics (number patterns, function algebra, proportion,
geometry , data analysis, statistics, probability and spatial sense) and biology (genetics).
II. ABSTRACT

Sickle cell anemia is a disease passed down through families in which red blood cells form an abnormal crescent
shape. (Red blood cells are normally shaped like a disc.)
According to Bediako, Shawn, et.al, the present study examined an exploratory model of the confluence of racial
centrality, pain, psychological variables, and health care use in a sample of African American adults with sickle
cell disease.

SCD affects an estimated 70,000 to 100,000 Americans.

The disease occurs in about 1 out of every 500 African Americans births.

The disease occurs in about 1 out of every 36,000 Hispanic Americans births.

Sickle cell trait occurs in about 1 in 12 African Americans.
III. THEMES, CONCEPT/ BIG IDEAS:

Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin S changes the
shape of red blood cells, especially when the cells are exposed to low oxygen levels. The fragile, sickle-shaped
cells deliver less oxygen to the body's tissues. They can also get stuck more easily in small blood vessels, and
break into pieces that interrupt healthy blood flow.

Sickle cell anemia is inherited from both parents. If you inherit the hemoglobin S gene from one parent and
normal hemoglobin (A) from your other parent, you will have sickle cell trait. People with sickle cell trait do not
have the symptoms of sickle cell anemia.
IV.
GOALS AND OBJECTIVES:
The goals of the module are
BIOLOGY:
a. To demonstrate how sorting and recombination of genes results in genetic variation among offspring
(Indicator 1) .
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b. To demonstrate how traits are inherited including Punnett squares and pedigree analysis (Indicator 2)
c. To demonstrate the relationship between the structure of DNA and its role in determining traits
(Indicator 3)
d. To demonstrate beneficial and harmful effects of genetic alteration (Indicator 4)
MATH:
a. Students will collect data and determine the percent frequency of specific genes in a given population.
b. Students will focus on learning to reason and construct proof by estimating and comparing with a real
world model the frequency of sickle cell anemia in a population.
c. Students will communicate the mathematical data collected in their cooperative learning groups by
sharing that data to formulate a class average and by using that information to support a debate on
genetics.
d. Students will recognize the use of probability and percentages to analyze problems in real world
situations.
e. Students will develop mathematical skills such as averaging, using tables and using formulas .
f. Students will use computational tools and strategies such as prediction, basic mathematical skills and
algebraic formulas to analyze collected data.
g. Students will use genetic patterns and algebraic formulas to further their understanding of sickle cell
anemia.
h. Students will create a statistical graph of the class data and explore spatially through hands on activities
and demonstrations.
i. Students will collect, predict, organize, and represent data to answer questions based on genetics.
Students will discuss and support their opinions on the current topic of genetic testing of children in a
classroom debate.
V. PRE-REQUISITE KNOWLEDGE:
a.
b.
c.
d.
e.
f.
g.
VI.
BIOLOGY
Cell and its Structure
Biological Structure
Ecology
MATHEMATICS
Number patterns,
Algebra 1,
Geometry
Functions
Timeline: 4 LESSONS FOR ABOUT 2 WEEKS
2
VII. LESSON PLANS
LESSON PLAN NO. 1
KNOWING SICKLE CELL
By: FE ARENASA, JUDITH BEBORA, JULITA BELCHES REBECCA LANGOMES
Course: BIOLOGY
Class: ____________________________
Date:
_______________
DAY___________
Unit Title: GENETICS
Topic:
WHAT IS SICKLE CELL?
Materials:
Video Clips : The Creation, What is sickle Cell?, Worksheets, Calculator
MSDE CORE Standards:
MATH:
Quantities★ N -Q
Reason quantitatively and use units to solve problems.
1. Use units as a way to understand problems and to guide the solution of multi-step problems; choose and
interpret units consistently in formulas; choose and interpret the scale and the origin in graphs and
data displays.
2. Define appropriate quantities for the purpose of descriptive modeling.
3. Choose a level of accuracy appropriate to limitations on measurement when reporting quantities.
BIIOLOGY
EXPECTATION 3.3
The student will analyze how traits are inherited and passed on from one generation to another.
INDICATOR:
3.3.1 The student will demonstrate that the sorting and recombination of genes during sexual reproduction
has an effect on variation in offspring.
Lesson Objectives:
1. The Students will be able to describe sickle cell, reason and contrast proof by estimating and
comparing with a real world and its frequency in its population.
2. Students will collect data and determine the percent frequency of specific genes in a given
population.
Opening Activity/Warm-up:
Video Clip Showing: The creation: Students will make a cornell Note ( worksheet #1) of the formation of
the fetus.
Lesson Proper:
 Engagement of Students:
Problem Solving: If there are 2 sperms out of 500 to develop a Zygote out, what is the percentage of creating
a baby? Refer to video clip 1.
3

Exploration Activity: WICR ( Writing, Inquiring, Collaboration and Reading Strategy)
The class will be introduced to the topic of genetic diseases in a classroom discussion led by the
classroom teacher.
Perform Part I and part II of the Gene Pool Lab:
Selection of Environment with or without Malaria.
Then you should compare this result by creating a tabulated data, plotting a graph, and determine the
frequency .
Gene Pool labFor Teacher:
A Mutation Story link: http://www.pbs.org/wgbh/evolution/library/01/2/l_012_02.html
This segment tells the story of a genetic mutationaffecting the population of West Africa. Although helpful in
preventing malaria, this mutation can also lead tosickle cell anemia. Sickle cell specialist Dr. Ronald
Nagel stresses the genetic diversity required for the survival of a species.
Credits: © 2001 WGBH Educational Foundation and Clear Blue Sky Productions, Inc. All rights reserved.
For Student Worksheet:
Gene Pool Lab link: www.siprep.org/faculty/msullivan/documents/Genepoollab_001.doc
Part I. Selection in a malarial environment
Environment: Today, you are living in a poor country where malaria is a problem, and you cannot afford medication or
treatment to combat the effects of sickle cell anemia.
Procedures:
*Note: The teacher will record class data on the board; EACH student must record this information on their data table.
1. Choose one HbA and one HbS hemoglobin allele from the gene pool. (Generation 0)
2. RANDOMLY choose a student with whom to “mate.”
3. Face your partner with both allele index cards behind your back.
4. Perform the “mating dance” as shown by your instructor.
5. Count to 3 and then reveal one allele.
6. The TWO alleles (one from each student) represent your first child.
7. Record your results on your scratch sheet.
8.
Repeat steps 4-6 to produce a second offspring and record results.
9. NOTE: Individuals with TWO HbS alleles cannot survive in our environment. If you produce an offspring with
TWO HbS alleles, re-mate until you produce an offspring that is either HbA/HbA or HbA/HbS.
10. It has also been found that HbA/HbS individuals survive at a higher rate than HbA/HbA individuals.
a. If you are HbA/HbA, flip a coin to determine if you will live or die.
b. Heads= HbA/HbA survives
c.
Tails= HbA/HbA dies
If you die, re-mate following instructions 4-6 until you have a child that survives.
11. The first generation now dies, and each partner assumes the identity of one of the two offspring. *You may need
4
to return to the gene pool to fetch a new allele.
12. Determine which copies of hemoglobin alleles you have and QUICKLY move to the area designated below:

TWO HbA alleles= between lab bench 1 and 2

ONE HbA and ONE HbS allele= between lab bench 6 and 7
13. Teacher records # of each allele combination. This is generation 1.
14. Teacher will instruct you when you should go find another mate.
15. Repeat steps 2-13 for more generations as time allows. (Be sure that you are mating randomly.)
Part II. Selection in an environment WITHOUT malaria
Environment: Today, you are living in a poor country where malaria is NOT a problem, and you cannot afford
medication or treatment to combat the effects of sickle cell anemia.
Follow the procedures above as in part I. with the following CHANGES:
 In this environment, HbA/HbS individuals have LOWER fitness (survival and reproductive success) than
HbA/HbA
 Replace procedure 10. above with the following:
a. If you are HbA/HbS, flip a coin to determine if you will live or die.
b. Heads= HbA/HbS survives
c.

Tails= HbA/HbS dies
If you die, re-mate following instructions 4-6 until you have a child that survives.
Complete the data table, graphs and post lab analysis for Part II.
Part I-Data Tables and Graphs: For each generation, record the # of individuals with each of the three possible allele
combinations and then determine the frequency.
Population size= ________________ (number of individuals in the class
I. Effects of selection in a malarial environment
HbA/HbA
Generation
0
#
Frequency
HbA/HbS
#
Frequency
HbS/HbS
#
Frequency
1.0
1
2
3
4
5
6
7
8
5
9
10
HbA= normal hemoglobin allele
HbS= mutated hemoglobin allele
Graphs: You need to create a scale for the axes. Use the grid below to graph changes in frequency of each of the
allele combinations over time. Use different colors for each line; fill in the legend to show what each color line
represents.
Frequency of allele combinations
Changes in the frequency of allele combinations in malarial environment
Time (generations)
Legend:
HbA/HbA=
HbA/HbS=
HbS/HbS=
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 Explanation:
Answer the Post Lab analysis part of Gene Pool Lab.
In this discussion the teacher and students will share what they know about genetic diseases and how they
nd
relate to the information shown in the 2 video clip: What is sickle cell? Explain the frequency of malarial
environment where sickle cell develops.
http://video.about.com/rarediseases/Sickle-Cell-Disease.htm
 Extension/ Elaborate:
Think about this: Economic Cost
During 2005, medical expenditures for children with sickle cell disease averaged $11,702 for children with
Medicaid coverage and $14,772 for children with employer-sponsored insurance. 40% of both groups had at
least one hospital stay.
Sickle cell disease is a major public health concern. From 1989 through 1993, there was an average of 75,000
hospitalizations due to sickle cell disease in the United States, costing approximately $475 million.
How this data affects the economy? Explain. Point for debate: In this time of recession, will you agree that
the government will increase the budget for the hospitalization due to sickle cell disease?
http://www.cdc.gov/ncbddd/sicklecell/data.html
 Evaluation/Assessment:
 http://www.youtube.com/watch?v=9UpwV1tdxcs
 How did you find out the frequency ? What mathematical operations do you used?
 Why do we need to find out frequency of sickle cell? What is the mathematical impact to the real
world? If one for every 12 African American people has sickle cell, what is the percentage that has
sickle cell when there of 656 students in our school?
Homework:
 Use google engine to compare a person with or without sickle cell diseases.
 Make a documentary report for at least 2 or more websites
Accommodation and Modification:





Extended Time Response; Verbatim Instruction.
Provide calculator devices, highlighting of text, cornell note format is provided, reward system
Highlighting of text. Genetic flow should be discussed verbatim
Provide open ended sentences ready for explanation part. Simplifying instructions.
Give more pictures to visualize which is a sickle cell or a normal blood cell
7
WARM- UP WORKSHEET
#1
CORNELL NOTE
Name ________________________________________
date ____________________
TOPIC: ________________________________
Questions
Notes/Answers from the video clip
1. What are these little tiny objects found at the
beginning of the video?
2. How can you identify if these are sperms?
3. Where does the fertilization of the egg
occur?
4. How does fertilized egg grow or multiply?
5. In what way that the characteristics from the
parents will be transmitted to the newly
developed fetus?
8
WORKSHEET#2 Lesson plan no. 1
Answer the Pre lab questions : Gene Pool Lab
Pre-lab: Read over the information at the following four web link: Watch the PBS Evolution Web Video (A mutation story)
and read the backgrounder that is provided with the video, A case study of the effects of mutation, the “bad” gene, sickle
cell anemia: the first molecular look at a disease and LW pp 49-51. Use information from the readings and web video to
answer the following questions.
1. What causes an ineffective hemoglobin protein (poor transporter of oxygen) to be produced?
2. Designate a normal hemoglobin allele as HbA and the mutated hemoglobin allele as HbS.
a. Which combination(s) of alleles will cause an individual to show severe effects of sickle cell anemia?
b. Which combination(s) of alleles produce individuals that show NO affects of sickle cell anemia?
3.
Describe the effect of having one normal and one mutated hemoglobin (Hb) allele.
4. In the absence of medication, what do you think would happen to individuals with both copies of the mutated
allele? Explain.
5. Explain why the mutated allele is not wiped out of the African populations.
9
LESSON PLAN NO. 2
Sickle Cell and Malaria- A Mathematical Representation
By: FE ARENASA, JUDITH BEBORA, JULITA BELCHES REBECCA LANGOMES
Course: BIOLOGY
Class: ____________________________
Date: _____
DAY___________
Unit Title: GENETICS
Topic: Sickle Cell and Malaria- A Mathematical Representation
Materials:
Sickle cell disease data link:
http://www.cdc.gov/ncbddd/sicklecell/data.html
Evolution of sickle cell malaria link:
http://www.youtube.com/watch?v=1fN7rOwDyMQ-
MSDE CORE Standards:
MATH:
FUNCTIONS:
Reason quantitatively and use units to solve problems:
1. Understand that a function from one set (called the domain) to another set (called the range) assigns to
each element of the domain exactly one element of the range. If f is a function and x is an element of its
domain, then f(x) denotes the output of f corresponding to the
input x. The graph of f is the graph of the equation y = f(x).
2. Use function notation, evaluate functions for inputs in their domains, and interpret statements that use
function notation in terms of a
context.
BIIOLOGY
EXPECTATION 3.3
The student will analyze how traits are inherited and passed on from one generation to another.
INDICATOR:
3.3.2 The student will illustrate and explain how expressed traits are passed from parent to offspring.
3.2.2 The student will conclude that cells exist within a narrow range of environmental conditions and changes
to that environment, either naturally occurring or induced, may cause changes in the metabolic activity of the
cell or organism.
1.4.4 The student will determine the relationships between quantities and develop the mathematical model
that describes these relationships.
Lesson Objectives:
1. Students will communicate the mathematical data collected in their cooperative learning groups by sharing
that data to formulate a class average and by using that information to support a debate on genetics.
2. Students will predict the births and deaths of sickle cell mutation by using algebraic expressions;
3. Students will use computational tools and strategies by using prediction, basic mathematical skills and
algebraic formulas to analyze collected data.
Opening Activity/Warm-up:
Writing Literacy: Create a paragraph as reaction of your research( base from their homework)
10
Use the Writing Literacy format attached hereto. ( worksheet # 1 lesson plan 2)
Lesson Proper:
 Engagement of Students:
Watching video on the relationship of malaria and sickle cell:
http://www.youtube.com/watch?v=1fN7rOwDyMQLet them read the student reading assignment. Resource: A Study of Malaria and Sickle Cell Anemia:
A Hands-on Mathematical Investigation
Link: http://www9.georgetown.edu/faculty/sandefur/handsonmath/downloads/pdf/scel-s.pdf

Exploration Activity: WICR ( Writing, Inquiring, Collaboration and Reading Strategy)
Do the activity focus on simulation of genetic processes.
Activity title: Modeling a Population where Malaria is a Risk: A Physical Model
http://www9.georgetown.edu/faculty/sandefur/handsonmath/downloads/pdf/scel-s.pdf
Worksheet # 2 Lesson Plan 2 is attached hereto.
 Explanation:
Making a Mathematical Model of the Population
1. You have simulated the birth of a population by looking at 30 random "births" and modeling death events
with given probabilities. Study your table and those of other groups. Compare each others' results. The purpose
of the simulation was to help you understand the genetic process and the way the incidence of the two diseases
affects the survival rates of the children. In the following, you will investigate how the size of the surviving
population depends on the fraction of alleles in the parent population that are N. For example,
 suppose 60% of the alleles in the parent population are N and 40% are S. (This could be represented by
a cup containing 6 N beads and 4 S beads.) Imagine that you are going to draw beads from the cup at
random, replacing beads after each draw, to get 30 births, a total of 60 beads, two beads (thus two
alleles) for each new birth
 Instead of simulating births and deaths, you will predict them with numerical expressions based on
probabilities using the fractions you know describe the situation. You want to know the number of NN
individuals that should be expected in a total of 30 births if the fraction of N alleles in the adult
population is n= 0.6 . To compute this number, multiply the probability that one parent will contribute
an N allele times the probability that the other parent will contribute an N allele times the number of
births:
0.6 x 0.6 x 30 = 10.8 NN children
2. Use the tree or the area model in Figure 1a) or b) to help compute the expected number of children born
with "NS" and the expected number of children born with SS.
11
3. Let represent the fraction of the alleles of the parents that are N. Let represent the total number of 30
children that are expected to survive both malaria and sickle cell anemia, assuming that two-thirds of the NN
children die of malaria and none of the SS children survive sickle cell anemia. Find . Completing the column of
Table 2 under "0.6" will help you organize your information.
Solution:
Find 4 and . (For each, complete a tree diagram similar to Figure 1 and then complete the columns of Table 2
under "0.4" and "0.3".)
Show and explain your solution:
 Extension/ Elaborate:

Now write the function ƒ(n) for the number of the 30 children who achieve adulthood,
where n is the fraction of N alleles in the gene pool. You have probably written your expressions for the
last column of Table 2 in terms of both s and n. Rewrite your expressions in terms of n only. This will
help you to develop your expression of ƒ(n) . Recall that all the alleles are either S or N, so if n is the
fraction of one type, you can easily express s in terms of n.

Factor the function ƒ(n) .
Graph
Graph the function. Label units on horizontal and vertical axes. What do the numbers on the horizontal
axis represent? What do the numbers on the vertical axis represent? How do the -intercepts relate to the
factors?
12
 What is the domain of your function ƒ(n), in this context? That is, what values of n in this context?
That is what values of n are possible in the real world?
Watching more videos:
 http://www.youtube.com/watch?v=1fN7rOwDyMQ&feature=related
 http://www.youtube.com/watch?v=sAJMHpjARYI&feature=related
 http://www.youtube.com/watch?v=ujf72mjy0Bg&feature=related
 http://www.youtube.com/watch?v=9UpwV1tdxcs
 Evaluation/Assessment: Practice test
A Model with Varying Sickle Cell Survival Rate
 Suppose that 90% of NN children survive malaria and that 40% of SS children survive sickle cell
anemia. Remember that all of the "NS" children survive both diseases. Assume 1000 children are born.
 a. Develop a function ƒ(n) for the total number of children who survive both diseases if n is the
fraction of N alleles among the parents and s= 1-n is the fraction of S alleles among the parents. The
following tree diagram and/or area model may help.
 B. Find the zeros of ƒ(n). (Note that the roots do not have real world significance)
13
 C. Use the roots to find the n -value that maximizes the function ƒ(n). This –value gives the genetic
makeup that maximizes the number of children that survive.
 d. Graph ƒ(n). Include the roots of ƒ(n) in your graph, even though these values have no physical
significance.
Summary
 One reason that the sickle cell allele occurs with relatively high frequency in some human populations is
that, in areas where the malaria parasite thrives, the presence of the sickle cell allele results in the survival
of a larger fraction of the population. This is termed a "survival advantage." It is believed that this type of
relationship exists for other diseases and genetic traits. For example, there is some evidence that people
with just one of the alleles that causes cystic fibrosis have an increased chance of surviving cholera.
Another important aspect of the relationship between a disease and a new allele for a trait is worth noting.
Genetic mutations occur randomly over time, and a large population can generate a large, diverse number
of mutated genes. If the population of a species is small, such as in the case of an endangered species, there
are fewer potential opportunities for beneficial genetic mutations to occur that could help the species to
survive new dangers. Genetic diversity helps a species survive.
 Question: Based from mathematical representation, what are the factors that affect the population of sickle
cell patients?
 Based from the mathematical representation, can we consider SCD curable?
--------------------------------------------------------------------------------------------------------------------------------------
 HOMEWORK:
Research on genetic testing. Make a report about this topic.
__________________________________________________________________________________________
Accommodation and Modification:




Extended time response.
Provide calculator devices
Separate mathematical instruction should be provided by writing the steps in a separate text.
Highlighting of text especially the formula and equation.
14
Worksheet #1 Lesson plan 2
WRITING LITERACY ABOUT SICKLE CELL
Websites where your research taken: _______________________________________________________
In your paragraph below include the following items to describe sickle cell disease?
What is sickle cell? Is this a communicable disease?
How sickle cell diseases transfer from one offspring to another?
Can Sickle cell disease be attain from malaria victims? Give 2 or more supporting details about this.
Describe the physical characteristics of a person who has sickle cell.
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SIMULATION ACTIVITY
Activity title: Modeling a Population where Malaria is a Risk: A Physical Model
We are going to simulate the birth of children where there is a risk of malaria and sickle cell anemia. Assume
that this population is born into an area in which one-third of the NN children survived Malaria. Also assume
that none of the SS children survive sickle cell anemia. In the simulations, we will experiment with different
genetic make ups in a population (that is, different proportions of N and S alleles among the adults) to see
how the genetic makeup affects the number of children that survive both malaria and sickle cell anemia.
Complete the following simulation of the genetic process. This will help prepare you to develop a
mathematical model of the population. Before you begin, designate one person to hold the cup of beads, one
person to draw from the cup, and one person to record the data.
Simulation 1. Put four S beads and six N beads into a cup. This cup represents the initial genetic makeup of an
adult population in which the proportion of normal, N, alleles is and the proportion of sickle cell, S, alleles is
0.4.
 This models the adults of this population. You can now simulate the birth of the children of this
population. The designated drawer in your group should draw one bead at random from the cup, its
type should be recorded, and the bead should then be returned to the cup. Draw another bead from
the cup, record its type, and return this second bead to the cup.
At this point, you have recorded one of NN, "NS" (for either NS or SN), or SS. These are the alleles of the first
child. Repeat this process for a total of 30 "births." When you have completed the 60 draws (30 "births"), you
have some number of NN's, some number of "NS"'s and some number of SS's. These represent the 30 children
that were born. Now each SS dies of sickle cell anemia. The NN's are in danger of dying of malaria. In this
simulation, assume two-thirds of the NN children die from malaria. The number of children that survive to
adulthood equals the number of "NS" children plus one-third of the NN children. When we did this simulation,
we got a total of 1313 survivors, which we recorded in Table 1. Record your total in Table 1, in the space under
the 0.6. (Because your population represents an average number of survivors, your population may have a
fractional number of "people", as ours did.)
Table 1 Results of simulation with 1/3 of NN's surviving malaria
fraction of N alleles in adult
population
0.6
0.3
total number of 30 births that
survive to adulthood in our group
total number of 30 births that
survive to adulthood, class
average
16
Simulation 2: Repeat the process of Simulation 1, but this time use a cup with 7 S and 3 N beads. This cup represents
the genetic makeup of an adult population in which the proportion of normal, N, alleles is 0.3. Again, assume that of the
NN children die 23 from malaria and all of the SS children die from sickle cell anemia. Record your result in the space
under the 0.3 in Table 1.

You can see that the size of the population of surviving children is a function of the fraction of alleles among the
adults that are N. Call this function . In your simulation, what was the value of ? What value did you get for ? In
the context of this model, what is the domain and range of this function?
Table no. 2- Results of predictions when 1/3 of NN's survive malaria
Fraction of N alleles in adult population
0.6
0.4
0.3
n
Fraction of S alleles in adult population
Number or 30 births that are NN
Number of NN birth who survive Malaria
Number of births that are “NS”
Total number of 30 births that survive to adulthood
COMPARISON OF TABLE 1 AND 2
 Compare the last row of Table 1 to the last row of Table 2. Table 1 is a record of a
physical simulation; Table 2 is a mathematical prediction based on probabilities.
Assuming you pooled the results of all of the groups in your class on Table 1, you have a
reasonable picture of what might happen in some population. Compare that to Table 2.
 Neither the physical simulation nor the mathematical model should be thought of as a
completely accurate picture of what will happen in the real world in a given instance;
probabilities tell us what to "expect", but it is unusual for the real world to exactly mirror
the expected results.
 Instead of simulating births and deaths, you will predict them with algebraic expressions.
Let represent the fraction of N beads in the cup and let represent the fraction of S beads
in the cup. Compute symbolically, using and , the number of the 30 births that will be
NN and the number that will be "NS." Use these results to complete the last column of
Table 2. Completing the tree diagram in Figure 2 or the area model of Figure 3 may help.
17
Application: Consider your data as illustrated below:
______________________________________________________________________________
18
LESSON PLAN NO. 3
SICKLE CELL IN MOLECULAR LEVEL
By: FE ARENASA, JUDITH BEBORA, JULITA BELCHES REBECCA LANGOMES
Course: BIOLOGY
Class: ____________________________
Date: _____
DAY___________
Unit Title: GENETICS
Topic: Sickle Cell in Molecular Level
Materials: Sickle Cell Anemia: A Case Study Approach to Teaching High School Genetics
http://genetics-education-partnership.mbt.washington.edu/download/sicklecell.pdf
Life with sickle cell video clip link:
http://www.youtube.com/watch?v=KhLdthi89mU&feature=related
Gel electrophoresis link:
https://www.msu.edu/~russellr/portfolio/electrophoresis/electrophoresis.html?pagewanted=all
ABORTION statistics in United States Data and Trends link:
http://www.nrlc.org/Factsheets/FS03_AbortionInTheUS.pdf
Genetic testing and screening link :
http://www.thehastingscenter.org/Publications/BriefingBook/Detail.aspx?id=2176
Images for:
Glutamic acid
http://groups.molbiosci.northwestern.edu/holmgren/Glossary/Definitions/Def-G/Glutamic_acid.html
Valine
http://groups.molbiosci.northwestern.edu/holmgren/Glossary/Definitions/Def-V/Valine.html
MSDE CORE Standards:
MATH:
1.2 -Represent patterns and/pr functional relationships in a table, as a graph, and/or by mathematical
expression.
BIIOLOGY
3.3.2 The student will illustrate and explain how expressed traits are passed from parent to offspring
The student will analyze how traits are inherited and passed on from one generation to another.
Lesson Objectives:
Students are expected to learn that:
 Genotype gives rise to phenotype; the two inherited alleles for a gene determine the phenotype for the
trait
 DNA information provides instructions for building proteins
 the genetic information is encoded in DNA
19


Changes in DNA, or mutations, cause new alleles to arise, leading to variation among organisms within a
population
Genetics research has applications in many different fields; Genetics research raises many ethical, legal,
and social issues
Opening Activity/Warm-up:
Writing Literacy: Create a short paragraph with regards to the given concerns: ( Worksheet # 1 Lesson plan 3 supports
this acitivity.
Lesson Proper:
 Engagement of Students:
Watching video: Life With Sickle Cell
http://www.youtube.com/watch?v=KhLdthi89mU&feature=related
Life with Sickle Cell video/Sickle Cell Background
After watching the video Blood is Life and reading the handout Sickle Cell Anemia and Genetics:
Background Information, answer the following questions. ( Write your brief answer in the writing lieteracy
format)
1. Patient Girl has sickle cell anemia. Describe her symptoms.
2. Describe the structure of hemoglobin. (How many chains are there? What types? Why is
iron necessary for blood?)
3. How does sickle hemoglobin differ from normal hemoglobin?

Exploration Activity: WICR ( Writing, Inquiring, Collaboration and Reading Strategy)
.
Let them perform the activity on Sickle Cell at the Molecular Level Activity (adopted from
https://gsoutreach.gs.washington.edu/files/sickleactivity_05-2007.pdf)
Attached herewith is worksheet #2 Lesson Plan 3
 Explanation:
Discussion of the analysis questions about the effect of changing one amino acid.
Focus on the concept:
Although the altered β globin has only one amino acid changed out of the total of 146, it’s a
crucial amino acid. When this new amino acid is at position #6 instead of the correct amino acid,
the overall hemoglobin β chain becomes more hydrophobic. As a result, when the hemoglobin
chains fold into their 3-dimensional shape and assemble together, the resulting molecules tend to
STICK TOGETHER, forming long chains of hemoglobin.
This altered hemoglobin deforms the normally rounded cell into the sickle shape. These red
blood cells are destroyed at an increased rate, causing anemia. They are also prone to becomingstuck in
capillaries, causing pain, organ damage, and often premature death.
http://www.youtube.com/watch?v=XuUpnAz5y1g&feature=related – for the DNA movies ( genome)
20
 Extension/ Elaborate:
Introduce the use and importance of gel electrophoresis by allowing them to explore this site:
https://www.msu.edu/~russellr/portfolio/electrophoresis/electrophoresis.html?pagewanted=all
Perform the Sickle Cell Disease Diagnosis Lab. Use of gel electrophoresis.
 Evaluation/Assessment: Practice test
AUTHENTIC ASSESSMENT
Role Playing
Imagine that you are a genetic counselor. Based on your results, write a brief dialog (2–3 minutes) between
you and the parents of your family as you present them with the results of their genetic testing. Include what
the results say about the inheritance of sickle cell in
the family, and explain what the family members’ health situation and options are, both now and in the
future. Use an understanding tone, and be aware of sensitive issues. Be prepared to enact your scene in front
of the class if asked to do so.
Class debate
Is genetic screening should be a mandate? Pros and Cons
Should genetic changes that cause hereditary problems be diagnosed before birth? What are the pros and
cons? (For your information, scientists estimate that each of us carries one copy of at least six lethal recessive
genes.)
Math connection
Use the ABORTION statistics in United States Data and Trends. Make a graph to show the trends between
1973 – 2008. Make a connection of the year when genetic screening had been used on the trend increase of
abortion rate in the US.
PART 2- EVALUATION PROCESS:
Sickle Cell Anemia: Blood Video Questions and Translation Practice Worksheet
Blood video/Sickle Cell Background
After watching the video Blood is Life and reading the handout Sickle Cell Anemia and Genetics: Background
Information, answer the following questions.
1. Rosalyn has sickle cell anemia. Describe her symptoms.
2. Describe the structure of hemoglobin. (How many chains are there? What types? Why is iron necessary for
21
blood?)
3. How does sickle hemoglobin differ from normal hemoglobin?
Sickle Cell at the Molecular Level
In sickle cell anemia, there is a mutation in the gene that encodes the  chain of hemoglobin. Within this gene
(located on Chromosome 11), ONE BASE in the DNA is replaced with another base, and this mutation causes
the normal amino acid #6 to be replaced by another amino acid.
1. Making a Normal Beta Chain of Hemoglobin
The sequence below is the first part of the DNA sequence for the  chain of normal hemoglobin. Fill in the
complementary DNA strand using the base-pairing rules for making DNA (A pairs with T, C pairs with G).
DNA: GTG CAC CTG ACT CCT GAG GAG
DNA:
Now make the messenger RNA from the new, complementary strand of DNA that you just wrote down. Use the
RNA base-pairing rules (same as DNA but use U instead of T).
mRNA:
Now, using the Genetic Code chart in your textbook, translate this mRNA into a sequence of amino acids.
Amino Acids:
2. Making Sickle Cell Hemoglobin
In sickle cell anemia, there is a mutation at the seventeenth nucleotide of DNA in this gene; the nucleotide is
changed from A to T. Fill in the complementary DNA strand, mRNA, and amino acid sequence in the
hemoglobin protein.
DNA: GTG CAC CTG ACT CCT GTG GAG
DNA:
mRNA:
Amino Acids:
3. The Effect of Changing One Amino Acid
You can see that in normal hemoglobin, amino acid #6 is glutamic acid (Glu) and in sickle cell hemoglobin,
amino acid #6 is valine (Val). Observe the two structural formulas for these amino acids:
Note: if these amino acid figures do not display correctly on your browser, please refer to your textbook or to the pdf downloadable
version of this document.
22
H O
H O
| ||
| ||
��N��C��C��
��N��C��C��
| |
| |
H CH
H CH2
// \
|
CH3 CH3
CH2
|
C
// \
valine
O Oglutamic acid
Describe which amino acid is polar and which one is nonpolar. How can you tell which is which?
Although the altered  globin has only one amino acid changed out of the total of 146, it�s a crucial amino
acid. When this new amino acid is at position #6 instead of the correct amino acid, the overall hemoglobin 
chain becomes more hydrophobic. As a result, when the hemoglobin chains fold into their 3-dimensional shape
and assemble together, the resulting molecules tend to STICK TOGETHER, forming long chains of
hemoglobin.
This altered hemoglobin deforms the normally rounded cell into the sickle shape. These red blood cells are
destroyed at an increased rate, causing anemia. They are also prone to becoming stuck in capillaries, causing
pain, organ damage, and often premature death.
Summary
1. How does sickle cell hemoglobin differ from normal hemoglobin at the primary level of protein structure
(order of amino acids)?
2. How does sickle cell hemoglobin differ from normal hemoglobin at the fourth level of protein structure (the
sum of all the folded protein chains)?
3. What is the effect on the red cell containing this altered hemoglobin?
23
Genetics review
Let A=allele for normal hemoglobin and S=allele for sickle hemoglobin.
1. What inheritance pattern does sickle cell anemia follow? (dominant, recessive, or other?)
2. What is Rosalyn�s genotype?
3. If Rosalyn has a child, what are the chances the child would have sickle cell anemia if the father was a sickle
cell carrier? Show using a Punnett square.
________________________________________________________________________________________
 HOMEWORK:
Genetic testing and screening link :
http://www.thehastingscenter.org/Publications/BriefingBook/Detail.aspx?id=2176
Prenatal Testing and Abortion
It is extremely difficult to get good statistics on the number of pregnancies that are terminated following a
positive prenatal diagnostic result. However, the paucity of data is in keeping with the continued discomfort
with, and perhaps even increasing debate about the morality of, abortion in the United States. Thus, the goals
of prenatal testing—presented in patient education materials, doctors’ offices, and even in the professional
literature–emphasize information and reassurance, with pregnancy termination mentioned only in the context
of “reproductive choice.”
The limited available data suggest that rates of termination vary by genetic condition as well as the mother’s
background. The rate of termination is around 85% for Down syndrome and lower for less severe conditions.
Hispanic women are the least likely of all women to have abortions following prenatal testing. The California
State Genetic Disease Branch, which keeps the best records on pregnancies diagnosed with a severe neural
tube defect, suggest a large range, from less than 20% for Hispanics to more than 90% for all women
beginning prenatal care in the first trimester of pregnancy.
Make a podcast regarding this prenatal testing and abortion.
__________________________________________________________________________________________
Accommodation and Modification:




Extended time response.
Provide calculator devices
Separate mathematical instruction should be provided by writing the steps in a separate text.
Highlighting of text especially the formula and equation.
24
Worksheet #1 Lesson plan 3
WRITING LITERACY ABOUT SICKLE CELL
How normal cell differs from sickle cell?
What mathematical representation that happens in sickle cell formation?
QUESTIONS FOR THE VIDEO SHOWING: ENGAGEMENT
Patient Girl has sickle cell anemia. Describe her symptoms.
Describe the structure of hemoglobin. (How many chains are there? What types? Why is
Iron necessary for blood?
How does sickle hemoglobin differ from normal hemoglobin?
25
Worksheet #2 Lesson Plan 3 EXPLORATION
Sickle Cell Anemia and Genetics: Background Information
Adopted from: http://genetics-education-partnership.mbt.washington.edu/download/sicklecell.pdf
Genetics of Sickle Cell Anemia
Sickle cell anemia was the first genetic disease to be characterized at the molecular level. The mutation responsible for
sickle cell anemia is small—just ONE nucleotide of DNA out of the three billion in each human cell. Yet it is enough to
change the chemical properties of hemoglobin, the iron and protein complex that carries oxygen within red blood cells.
There are approximately 280 million hemoglobin molecules in each red blood cell (RBC). The protein portion of
hemoglobin consists of four globin subunits: two alpha (α) and two beta (β). These two types of subunits are encoded by
the α and β globin genes, respectively. While the binding of oxygen actually occurs at the iron sites, all four globin chains
must work together in order for the process to function well.
Sickle cell anemia, also known as sickle cell disease, is caused by a point mutation in the β globin gene. As a result of this
mutation, valine (a non-polar amino acid) is inserted into the β globin chain instead of glutamic acid (an electrically
charged amino acid). The mutation causes the RBCs to become stiff and sometimes sickle-shaped when they their load
of oxygen. The sickle cell mutation produces a “sticky” patch on the surface of the β chains when they are not complexed
with oxygen. Because other molecules of sickle cell hemoglobin also develop the sticky patch, they adhere to each other
and polymerize into long fibers that distort the RBC into a sickle shape.
The sickled cells tend to get stuck in narrow blood vessels, blocking the flow of blood. As a result, those with the disease
suffer painful “crises” in their joints and bones. They may also suffer strokes, blindness, or damage to the lungs, kidneys,
or heart. They must often be hospitalized for blood transfusions and are at risk for a life-threatening complication called
acute chest syndrome. Although many sufferers of sickle cell disease die before the age of 20, modern medical
treatments can sometimes prolong these individuals’ lives into their 40s and 50s.
There are two β globin alleles important for the inheritance of sickle cell anemia: A and S. Individuals with two normal A
alleles (AA) have normal hemoglobin, and therefore normal RBCs. Those with two mutant S alleles (SS) develop sickle
cell anemia. Those who are heterozygous for the sickle cell allele (AS) produce both normal and abnormal hemoglobin.
Heterozygous individuals are usually healthy, but they may suffer some symptoms of sickle cell anemia under conditions
of low blood oxygen, such as high elevation. Heterozygous (AS) individuals are said to be “carriers” of the sickle cell trait.
Because both forms of hemoglobin are made in heterozygotes, the A and S alleles are codominant.
About 2.5 million African-Americans (1 in 12) are carriers (AS) of the sickle cell trait. People who are carriers may not
even be aware that they are carrying the S allele!
Sickle Cell Anemia and Malaria
In the United States, about 1 in 500 African-Americans develops sickle cell anemia. In Africa,
about 1 in 100 individuals develops the disease. Why is the frequency of a potentially fatal
disease so much higher in Africa?
The answer is related to another potentially fatal disease, malaria. Malaria is characterized by
chills and fever, vomiting, and severe headaches. Anemia and death may result. Malaria is caused
by a protozoan parasite (Plasmodium) that is transmitted to humans by the Anopheles mosquito.Contributed by Jeanne
Ting Chowning, BioLab, Seattle, WA
When malarial parasites invade the bloodstream, the red cells that contain defective hemoglobin
become sickled and die, trapping the parasites inside them and reducing infection.
26
Compared to AS heterozygotes, people with the AA genotype (normal hemoglobin) have a
greater risk of dying from malaria. Death of AA homozygotes results in removal of A alleles
from the gene pool. Individuals with the AS genotype do not develop sickle cell anemia and have
less chance of contracting malaria. They are able to survive and reproduce in malaria-infected
regions. Therefore, BOTH the A and S alleles of these people remain in the population. SS
homozygotes have sickle cell anemia, which usually results in early death. In this way, S alleles
are removed from the gene pool.
In a region where malaria is prevalent, the S allele confers a survival advantage on people who
have one copy of the allele, and the otherwise harmful S allele is therefore maintained in the
population at a relatively high frequency. This phenomenon will be examined in the Allele
Frequencies and Sickle Cell Anemia Lab, which relates the change in allele frequency in a
population to evolution.
The frequency of the S allele in malaria-infected regions of Africa is 16%. The sickle cell allele
is also widespread in the Mediterranean and other areas where malaria is or used to be a major
threat to life. In contrast, the S allele frequency is only 4% in the United States, where malaria
has been virtually eliminated. Malaria was once common in the United States, but effective
mosquito control caused the number of cases to drop. Recently, however, there has been an
increase in the number of malarial cases because of increased travel, immigration, and resistance
to medication. In Southern California there was a 1986 outbreak of nearly 30 cases of malaria
transmitted by local mosquitos!
Sickle Cell Anemia and Current Research
The oxygen requirements of a fetus differ from those of an adult, and so perhaps not
surprisingly, prenatal blood contains a special hemoglobin. Fetal hemoglobin contains two
gamma (γ) globin polypeptide chains instead of two adult β chains. After birth, the genes
encoding γ globin switch off, and the ones encoding β globin switch on. Understanding how this
genetic switch works could allow researchers to understand much about the control of genes in
general and sickle cell anemia in particular.
Indian and Saudi Arabian people have a milder variation of sickle cell anemia, sometimes with no
symptoms. In this population twenty-five percent of each person’s hemoglobin is the fetal kind.
Similarly, the blood of adults with an inherited condition called “hereditary persistence of fetal
hemoglobin” also contains fetal hemoglobin and these individuals are healthy. Some people
with this condition completely lack adult hemoglobin and still show no ill effects. Biochemical
experiments have demonstrated that, in a test tube, fetal hemoglobin inhibits polymerization of
sickle cell hemoglobin. These observations suggest that increasing fetal hemoglobin levels may
be an effective treatment for sickle cell anemia. There are a number of lines of research related to
activation of fetal hemoglobin as a therapy for sickle cell anemia:
• Some infants whose mothers suffered from diabetes during pregnancy have unusually high
concentrations of the biochemical butyrate in their blood plasma. Butyrate is a natural fatty
acid that stimulates RBCs to differentiate from their precursors (reticulocytes). Butyrate also
prevents the γ globin gene from switching off and the β globin gene from switching on in these
infants, who are healthy despite lacking adult hemoglobin. When butyrate is given to patients
with sickle cell anemia, the γ globin mRNA levels in reticulocytes increase significantly.
Perhaps butyrate or other chemicals that stimulate fetal hemoglobin production could be used
to treat sickle cell anemia.Contributed by Jeanne Ting Chowning, BioLab, Seattle, WA
• In 1983, a drug called hydroxyurea (HU) was first used on sickle cell patients to try to activate
their fetal globin genes. By 1995, clinical trials had demonstrated that HU could increase fetal
hemoglobin levels in patients’ RBCs and prevent the cells from sickling. Patients treated with
HU experienced less frequent and severe painful crises. However, hydroxyurea can be quite
toxic when used continuously to maintain elevated levels of fetal hemoglobin and can increase
the risk of leukemia.
• In 1992, it was found that alternating hydroxyurea with erythropoiten and providing dietary
iron raised the percentage of RBCs with fetal hemoglobin and relieved the joint and bone pain
27
of sickle cell disease. Erythropoiten is made in the kidneys and helps anemic patients replenish
their RBCs. It can be manufactured for therapeutic use with recombinant DNA technology.
• Mice that have been genetically engineered to contain a defective human β globin gene have
symptoms typical of sickle cell anemia, making them an ideal model for laboratory
experimentation. In 2000, these mice were mated to another transgenic mouse line expressing
human fetal hemoglobin. When compared to their sickle cell parents, the offspring had greatly
reduced numbers of abnormal and sickled RBCs, increased numbers of RBCs overall (reduced
anemia), and longer lifespans. These experiments established that only 9-16% of hemoglobin
need be the fetal type in order to ameliorate the sickle cell symptoms, and are an important first
step in a gene therapy solution to sickle cell disease.
Sickle Cell at the Molecular Level Activity
Adopted from: https://gsoutreach.gs.washington.edu/files/sickleactivity_05-2007.pdf
Introduction
In sickle cell anemia, there is a mutation in the gene that encodes the β chain of hemoglobin.
Within this gene (located on Chromosome 11), ONE BASE in the DNA is replaced with
another base, and this mutation causes the normal amino acid #6 to be replaced by another
amino acid.
1. Making a Normal Beta Chain of Hemoglobin
The sequence below is the first part of the DNA sequence for the β chain of normal hemoglobin.
Fill in the complementary DNA strand using the base-pairing rules for making DNA (A pairs
with T, C pairs with G).
DNA: GTG CAC CTG ACT CCT GAG GAG
DNA: _______________________________
Now make the messenger RNA from the new, complementary strand of DNA that you just
wrote down. Use the RNA base-pairing rules (same as DNA but use U instead of T).
mRNA: _____________________________________________________________
Now, using the Genetic wheel Code chart below, translate this mRNA into a sequence of
amino acids.
Amino Acids: _________________________________________________________
ANALYSIS QUESTIONS:
3. The Effect of Changing One Amino Acid
You can see that in normal hemoglobin, amino acid #6 is glutamic acid (Glu) and in sickle cell
hemoglobin, amino acid #6 is valine (Val). Observe the two structural formulas for these amino
acids:
28
Describe which amino acid is polar and which one is nonpolar. How can you tell which is which?
Although the altered β globin has only one amino acid changed out of the total of 146, it’s a crucial amino acid. When this
new amino acid is at position #6 instead of the correct amino acid, the overall hemoglobin β chain becomes more
hydrophobic. As a result, when the hemoglobin chains fold into their 3-dimensional shape and assemble together, the
resulting molecules tend to STICK TOGETHER, forming long chains of hemoglobin.
This altered hemoglobin deforms the normally rounded cell into the sickle shape. These red blood cells are destroyed at
an increased rate, causing anemia. They are also prone to becoming stuck in capillaries, causing pain, organ damage,
and often premature death.
Summary
1. How does sickle cell hemoglobin differ from normal hemoglobin at the primary level of protein structure (order of amino
acids)?
2. How does sickle cell hemoglobin differ from normal hemoglobin at the fourth level of protein structure (the sum of all the
folded protein chains)?
3. What is the effect on the red cell containing this altered hemoglobin
Genetics review
Let A=allele for normal hemoglobin and S=allele for sickle hemoglobin.
1. What inheritance pattern does sickle cell anemia follow? (dominant, recessive, or other?)
29
2. What is Rosalyn’s genotype?
4.
If Rosalyn has a child, what are the chances the child would have sickle cell anemia if the father was a sickle cell
carrier? Show using a Punnett square
Genetic Code Wheel Chart
link: http://www.millerandlevine.com/circular.html
30
2. Making Sickle Cell Hemoglobin
In sickle cell anemia, there is a mutation at the seventeenth nucleotide of DNA in this gene; the
nucleotide is changed from A to T. Fill in the complementary DNA strand, mRNA, and amino
acid sequence in the hemoglobin protein.
DNA: GTG CAC CTG ACT CCT GTG GAG
DNA: ______________________________
mRNA: ______________________________
Amino Acids: ______________________________
Worksheet #3- Lesson Plan 3
Sickle Cell Disease Diagnosis Lab
Student Instructions and Questions
Objective: To simulate the diagnosis of sickle cell anemia with DNA restriction analysis.
Background: The “DNA” you will receive has, in this simulation, already been “cut” by the Mst II
restriction enzyme. You will separate the resulting fragments of DNA by gel electrophoresis in order to
diagnose the genotypes of all members of a family. Families 1 and 2 each have a mother, father, teenager,
and fetus. Family 3 has a mother, and her two children, who are fraternal twins. Known samples will
also be run for comparison. In this family, the mother’s husband, now deceased, had a brother with
sickle cell anemia.
DNA and dyes are ‘charged’ molecules that can be separated by gel electrophoresis. The dyes we will use
are charged in solution, just as DNA is. They will therefore move from the
BLACK cathode (- end) to the RED anode (+ end). (Remember, negatively charged molecules such as
DNA “run towards the red.”)
Procedure:
1. Get tubes containing the “DNA” samples from your teacher. Record whether you have Family #1, #2,
or #3 in your lab notebook. The tubes are coded as follows (Note: each group will not necessarily receive
all tubes shown below).
Mother M
Father F
Teenager T
Twin 1 (Sondra) T1
Twin 2 (Jason) T2
Fetus O
Known Normal N
Known Carrier C
Known Sickle Cell Patient S
2. Slide the gel into the box, wells facing up and closest to the black electrode.
3. Using a P-20 micropipet set to 8 µl, load each well in the gel with the samples. Take turns loading with
others in your group, making sure to use a new tip each time.
4. Draw a gel as shown below and indicate in your lab notebook which sample you put in which lane.
Label this RESULTS. Draw the + and - ends of your gel so you remember the orientation.
31
Figure 1. Sample Results diagram for lab notebook.
5. If necessary, add more 1X TAE Buffer to the gel box so that the gel is adequately covered. (The buffer should cover
the gel by about 1-2 mm.) Connect the electrodes to the gel box and to the power supply (red to red, black to black).
6. Turn on the power supply and set it at about 120V. Run the gel for at least 10 minutes. While your gel is running, make
a second drawing of a gel showing what results you expect for the three known samples. Label this PREDICTIONS.
7. Turn off the power supply, unplug the electrodes, and open the gel box. Lift the gel and deck and slide the gel back into
the dish, pouring off extra buffer. For better viewing, place the dish on white paper. Color the pattern observed into your
RESULTS drawing.
8. If desired, preserve an image of your gel by transferring the dyes to Whatman blotter. Place gel on plastic wrap on
bench. Place one piece of Whatman paper cut to fit gel on top of gel. Place one piece of acetate (overhead transparencies
work great) cut to fit gel on top of Whatman paper. Place a book on top to provide weight. Wait about 10 minutes for
transfer.
9. Throw away the gel and pour back buffer!! Put all equipment back into the supply box.
Analysis:
1. Intrepret the results of the tests:
32
• Which family members have the sickle cell genotype (SS)?
• Which family members have the carrier genotype (AS)?
• Which family members have the normal genotype (AA)?
2. Draw a pedigree showing inheritance of sickle cell anemia in the family you analyzed.
EXTENSION: Connecting with Mathematics.
3. Make a Punnett Square and explain the probabilities of various genotypes and phenotypes
for offspring given the parents’ genotypes. (Be sure that your square includes a key;
A=normal allele, S=sickle allele).
Open this Link to : http://faculty.stcc.edu/BIOL102/Lectures/lesson3/punnett.htm to answer the following electronic
activity:
Why do we need to learn about Punnett squares?
Punnett squares enable one to understand the probabilities involved in passing alleles to the next generation. They are
rather straightforward when done for monohybrid crosses. In principles of biology II, you will continue with genetics and
need to apply Punnett squares to dihybrid crosses, too. But that is not necessary right now.
What is a Punnett Square and how do we use it?
A Punnett Square is simply a tool to help you understand how alleles are passed to the next generation. It enables you
to follow each parental allele as it could get passed to the next generation.
33
The punnett square has four boxes in it. These boxes get filled out by writing the alleles from the side along their row
and by writing the alleles from the top along their column. To see this done step-by-step, follow this link. Once filled
out, those four boxes represent all the possible genotypes that can exist in the next generation. These genotypes are
random combinations of the parent alleles.
Each of the four possible genotypes in the Punnett square have an equal chance of occurring. Of course, in the above
cross, all four are the same. So let's figure out the ratio of possible phenotypes and/or genotypes in the next generation:
Yy x Yy.
Note that when these two heterozygotes cross, their are 2 possible
phenotypes in the next generation, and three possible genotypes.
2 Phenotypes: yellow peas and green peas
3 Genotypes: homozygous dominant, heterozygous, and
homozygous recessive.
And, each of the F2 offspring represented by each box has an equal
chance of occurring. So, one is just as likely to get a YY individual out
of this cross as they are to get a yy individual.
Because of these equal probabilities, we can figure out what the
likelihood is for getting a green pea producing plant in the next
generation. Out of four possibly progeny, only one could have green peas. So our chance is 1/4, which is 25%. Another
way to describe this is to say that 1 could have green peas while 3 would not, so the ratio of green peas to non-green peas
is 1:3. The ratio of yellow peas to non-yellow peas is 3:1, and the likelihood of getting a plant with yellow peas is 75%.
Keep in mind that 3:1 is not 66.7%. With ratios, one has to say that for every three plants there is one other that is
different, so that 3 out of 4, or 3/4 (75%), is how you get the percentage. Ratios are hard. I'll give you one more example.
What percentage of the above cross end up as heterozygotes? Click here to check your answer! What percentage are
homozygous dominant? Click here to check your answer! What percentage are homozygous recessive? Click here to
check your answer! I'll bet that you figured out these genotype percentages. Now let's do the genotype ratios. What is
the ratio of homozygous dominant to heterozygous to homozygous recessive offspring? I'll give you a hint-- just count
them up (like we did with the phenotype ratios). Have you figured it out? If you think so, click here to check your
34
answer!
Consider something more important... at least to me. I told you above that I am a carrier for Tay Sachs disease. That
means that I am heterozygous for the gene affected-- such that I have one normal allele and one Tay Sachs allele. The
Tay Sachs allele is recessive. Knowing all this, what are the chances that I could have a child with Tay Sachs if I have a
child with:
someone who is homozygous dominant-- check!
someone who is heterozygous like me-- check!
I could not have a child with someone who is homozygous recessive, because that person would have had Tay Sachs and
would have died by the time they were 5 years old. Meanwhile, since it is totally random as to which alleles combine,
even if there is only a small chance to have a child with the disease, it is possible that every child I have with another
heterozygote would have it.
You see, probability is like flipping a coin. There might be a 50% chance that when you flip a coin it will end up
heads, but it is also possible to flip it 5 times in a row and get heads each time. There was only a 25% chance that my
parents could have a child with an eye color other than brown, they only had two children, and one of us (half) have
brown eyes (me) while the other one (my sister) has green eyes. Mendel did thousands of crosses-- and with thousands,
the numbers end up approximating the predictions. But with only a few offspring, like people tend to do, the numbers
within a family do not always match the probabilities.
The fact that a parent randomly gives one allele out of its two to the next generation is something that Mendel figured
out. We now call that Mendel's law of segregation. This is described on page 65, and it is the very last section of
chapter 3 that you need to read. However, one thing precedes that-- the discussion about sickle cell anemia. That is next.
Sickle cell anemia
Your book describes sickle cell anemia. An "anemia" is any problem that causes you to have too little oxygen in your
blood. With sickle cell anemia, the problem is with the molecule inside of red blood cells that carries oxygen through
your blood-- the molecule is hemoglobin. Sickle cell hemoglobin is less able to carry oxygen through the blood than
regular hemoglobin. Hemoglobin is often represented with the letters Hb. With sickle cell anemia, the way that the
hemoglobin is messed up causes the entire red blood cell to collapse on itself into a sickle shape and to be less flexible.
This causes additional problems for the person with this type of red blood cell.
The way sickle cell anemia is inherited is the same as any other trait that has dominant and recessive forms. The
diseased form is recessive, and the normal one is dominant. You would think that this would be represented by something
like N and n or HbN and Hbn, but it is not. The lettering to abbreviate this disease is a little more complicated-- but the
inheritance is not. Keep that in mind.
The normal hemoglobin gene is represented by HbA and the sickle cell hemoglobin gene is represented by HbS. A
person who has two normal alleles is then represented by HbA/HbA, where the "/" is used to help you see the two alleles
clearly from one another. There are some different crosses that could be made between people with the disease and those
without, or between carriers for the disease. Some crosses are:
HbA/HbA x HbS/HbS (normal x sickle cell)
HbA/HbA x HbA/HbS (normal x sickle cell carrier)
35
Extension activity
Use the chart on ABORTION statistics in United States Data and Trends. Make a graph to show the trends
between 1973 –2008.
Reported Annual Abortions
1973 – 2008
Based on this chart, make a connection of the year when genetic screening had been used on the trend
increase of abortion rate in the US. Support your answer with a research. Use internet sources to learn more
about genetic screening and pre-natal screening which may have connection with abortion.
____________________________________________
36
Worksheet # 4- Lesson Plan3
Gel Electrophoresis
This page displays and describes the "Gel Electrophoresis" interactive that is a part of Randy Russell's online
portfolio. To view this interactive, you need the Shockwave Director plugin (from Macromedia) installed in
your web browser. Details about this interactive (how to use it, and the project it was created for) appear lower
on this page, below the electrophoresis activity.
Can you determine which of the proteins (hemoglobin, actin, myosin) are found in the liver and muscle tissue
samples? Click the "Instructions" button in the upper left corner of the interactive for basic operating
instructions.
Go to this link to view:
https://www.msu.edu/~russellr/portfolio/electrophoresis/electrophoresis.html?pagewanted=all
I originally developed this interactive for introductory biology courses at Michigan State University. Modified
forms of it are also being used in graduate level Medical Technology courses (MT 830: Concepts in Molecular
Biology & MT 831: Clinical Application of Molecular Biology) at MSU that I helped produce as part of my
work for MSU's Virtual University.
Note that the interactive is "data-driven", in the sense that the positions of the bands for each sample are
controlled by simple numerical list variables (and are not "hard-coded" into the animation artwork). It is thus
quite simple to modify the activity to support different samples with different banding patterns, enabling
flexible use of the activity for a range of example cases per the course instructor's wishes.
Basic concept of electrophoresis
Gel electrophoresis is used to analyze DNA or proteins. After using enzymes to cut the long DNA or protein
strands, the DNA or protein. sample is placed in a "well" along the top of the jello-like gel. Next, current is
applied to the gel, and the electrically charged constituents of the sample migrate through the gel towards the
edge away from the wells. Strongly charged pieces tend to migrate more quickly. Also, larger pieces migrate
more slowly, since they have more difficulty slipping through the gel's matrix. By comparing the banding
patterns of samples with know substances, scientists can learn about the DNA or protein fragments. Repeated
experiments with different enzymes that cut at different locations help scientists determine the makeup of the
DNA or protein. sample.
In the version of the electrophoresis activity shown here, the goal is to determine which of the proteins
(hemoglobin, actin, and myosin) are present in liver and muscle tissue samples. The tissue samples contain
multiple proteins Can you determine which bands in the tissue samples, if any, match up with the proteins
(indicating the presence of the protein. in the tissue)?
37
LESSON PLAN NO. 4
MUTATION AND THE EFFECTS OF SICKLE CELL
By: FE ARENASA, JUDITH BEBORA, JULITA BELCHES REBECCA LANGOMES
Course: BIOLOGY
Class: ____________________________
Date: _______________
DAY___________
Unit Title: GENETICS
Topic: MUTATION AND THE EFFECTS OF SICKLE
Reference: http://www.concord.org/~btinker/workbench_web/unitV/act4B.html
Materials: * Worksheet: Protein Malfunction and Disease: Making a Sickle Cell Mutation (Student) [PDF version]
* Protein Malfunction and Disease: Making a Sickle Cell Mutation (Teacher)
Links: http://www.youtube.com/watch?v=RN2MKOx9wZU
Post Test
MSDE CORE Standards:
MATH:
Make geometric constructions
12. Make formal geometric constructions with a variety of tools and methods (compass and straightedge, string,
reflective devices, paper folding, dynamic geometric software, etc.). Copying a segment; copying an angle; bisecting a
segment; bisecting an angle; constructing perpendicular lines, including the perpendicular bisector of a line segment;
and constructing a line parallel to a given line through a point not on the line.
13. Construct an equilateral triangle, a square, and a regular hexagon inscribed in a circle.
BIIOLOGY


3.3.4 The student will interpret how the effects of DNA alteration can be beneficial or harmful to the individual,
society, and/or the environment.
Assessment limits:



mutations
chromosome number (abnormalities)
genetic engineering (gene splicing, recombinant DNA, cloning)
Lesson Objectives:
At the end of the lesson you should be able to interpret how the effects of DNA alteration can be beneficial or harmful
to individual by:
a. Comparing the effect of nucleotide substitutions and deletions on protein structure; and its reason about the
molecular origin of disease;
b. Relating the change in the structure of proteins to changes in their function and possible implications for human
health.
c. Create a formal geometric construction to describe the development of a sickle cell
Opening Activity/Warm-up:
There are two models in this activity, and they can be launched in one of two ways:
1. From your browser. Click the link below.:
* Molecular Workbench: Mutations
38
[http://xeon.concord.org:8080/modeler/webstart/protein/mutations.jnlp]
* Molecular Workbench: Hemoglobin
[http://xeon.concord.org:8080/modeler/webstart/protein/hemoglobin.jnlp]
2. By going through the Molecular Workbench application on your computer (workbench.jar), click the following links:
Student Pages, Protein Folding, Mutations or Hemoglobin.
It may take a short while to launch the Molecular Workbench the first time.
Lesson Proper:
 Engagement of Students: How Sickle Cell Mutate? Watch this video and in 2 sentences
answer the questions.
Open link to: http://www.youtube.com/watch?v=RN2MKOx9wZU

Exploration Activity: WICR ( Writing, Inquiring, Collaboration and Reading Strategy)
For Teacher: Best result if this can be done by group. Divide the class into 3 groups after they have seen the Mutation
story. ( Recall this video)
A Mutation Story link: http://www.pbs.org/wgbh/evolution/library/01/2/l_012_02.html
This segment tells the story of a genetic mutationaffecting the population of West Africa. Although helpful in
preventing malaria, this mutation can also lead tosickle cell anemia. Sickle cell specialist Dr. Ronald
Nagel stresses the genetic diversity required for the survival of a species.
Credits: © 2001 WGBH Educational Foundation and Clear Blue Sky Productions, Inc. All rights reserved.
I. Exploring two ways mutations occur: substitution and deletion. Distribute the Mutation Worksheet (Student). In this
activity students model DNA mutations and look at the effects on the shape of the protein fragment. It is important to
discuss with the students that the model does not show the intermediate steps of translation and transcription. Instead
the model shows the cause and effect between a mutation and protein structure. Nonetheless, students will be
expected to analyze what is happening keeping the intermediary steps in mind. Make sure that you discuss student
responses after they have completed the activity.
II. Understanding Sickle Cell Anemia. This concludes students exploration into the molecular mechanism related to Sickle
Cell Disease. Students compare the DNA code for normal and sickle cell hemoglobin, observe the difference in protein
structure and learn about how the difference in structure is related to the presence of disease symptoms. Distribute the
worksheet Malfunction and disease: Making a Sickle Cell Mutation.
III. GEOMETRIC FIGURE OF SICKLE CELL. Let the students acquaint the different figure of sickle cell. Let them trace the
different geometric angle that happens during mutation. Let them label the geometric figure as to the steps in forming
sickle cell. Worksheet #4
 Explanation:
Presentation of Outputs: Group 1- Two Ways of Mutation
Group 2- Malfunction and Disease: Mutation of Sickle Cell
Group 3 – Geometric Figure of Sickle Cell Mutation
39
 Extension/ Elaborate:
1.
Watch the DNA animations: Write your reactions in your thought column. For every animations, write at
least 2 comments or reaction. Link to:
http://www.hhmi.org/biointeractive/dna/animations.html
Watch the video: http://www.youtube.com/watch?v=_HhUpT3g-m8
2. Group Sharing:
What are the effects of sickle cell? How can you help the patient with sickle cell disease?
 Evaluation/Assessment:
1. Post Test link to: http://www.concord.org/~btinker/workbench_web/unitV/post_test.html
2. Project Making: Vodcasting:
Steps on how to make vodcast is found in this link : http://www.macworld.com/article/46066/2005/07/howtovodcast.html
Homework/ Project Making:
a. Create a Podcast about documentary of sickle cell disease. In this project includes mathematical
aspect such as the percentage of African-American students who are experiencing sickle cell
disease,
Let's take a quick look at each section of the podcast tutorial.
Plan Your Podcast
I know you are probably anxious to press record and get your voice on the net. But a little planning will help you stay
focused. In the end you will produce a better podcast that will attract and keep more listeners. This will also make
your job as a podcaster a lot easier.
In the planning section I will raise a few questions for you to consider and help you make some important decisions
about:

Podcast Topic

Podcast Format

Choosing a location for your podcast
We'll also talk about how to outline and plan each episodeof your podcast before you record.
Produce Your Podcast
This is where you will open the mic and start talking (or whatever else you plan on doing in your podcast). In this
section, I'll go over podcasting gearand podcasting software.
We'll also learn how to record your podcastand create an MP3 file in the Audacity Tutorial.
Publish Your Podcast
Once you've created your first podcast, you need to prepare it for publishing and post it to the internet. This section
40
covers topics such as:

Creating an MP3 File

ID3 Tags for Podcasts

Podcast Hosting (blogs, web hosting, RSS feeds)

Free Podcast Hosting

Naming Your Podcast File

Uploading Your Podcast

Writing Podcast Show Notes

Posting Show Notes
Promote Your Podast
Of course you'll want more listeners for your podcast. You want to become a recognized expert and celebrity on the
internet now that you have your own show, right?
In this section we'll talk about how to find listeners for your podcast.
•
Follow up activities of the lesson may include having groups of students research other genetic diseases on
the Internet. For example, students could research albinoism, cystic fibrosis, or color blindness and present the
information they find to the class.
•
Students also could research possible carriers that involve the use of genetics and DNA testing, such as,
genetic counselors or forensic researchers.
Accommodation and Modification:





Extended Time Response; Verbatim Instruction.
Provide calculator devices, highlighting of text
Highlighting of text. Genetic flow should be discussed verbatim
Provide open ended sentences ready for explanation part. Simplifying instructions.
Give more pictures to visualize which is a sickle cell or a normal blood cell
41
Worksheet #1 Lesson Plan 4
Discuss the Molecular Machines and Tools Chart, considering hemoglobin as a molecular machine, together with the
many other critical and specific jobs proteins perform in the cell. Ask students to think about what change in the body
would occur if any of these molecular machines on the chart would be mutated. What might happen if those molecules
could not perform their job well or at all? (Accuracy here is less important than their attempt to think through some
implications. With a deformed hemoglobin, a cell could not carry oxygen where it is needed.) You might also discuss
some environmental sources of mutation, e.g. radiation.
SOME PROTEIN JOBS: MOLECULAR COUNTERPARTS TO OUR "REAL WORLD" MACHINERY, AND MORE
SOURCE: LINK TO: http://www.concord.org/~btinker/workbench_web/unitV/molecular_counterparts.html
Proteins make up the machinery of our cells, most working by converting energy in an ATP molecule into force. They
use energy (delivered to them by ATP) to drive metabolic reactions, do mechanical work, such as moving muscles,
rotating cilia and flagella, and transporting substances across membranes. Carbohydrates supply the energy to
make ATP, nucleic acids the coded information and lipids play many roles, a particularly important one being
membrane composition. This chart develops the idea of proteins as "machines", chains that are shaped to do
specific jobs in the cells. Some jobs in a cell have counterparts in the tools and machinery used in the human world.
(Some, of course, are quite different, but that's a story for another page...)
EXAMPLE OF
MACHINE
FUNCTION
MOLECULAR
TOOLS OR
IMAGES OF WORKING PROTEINS
MACHINES
Structures
Transmit force;
Microtubules
reinforce Transmit made of tubulin,
tension, maintain
Tracks ,
shape
cables,
filaments,
beams, struts,
cross-links,
pipes
collagen
Long hollow tubes
http://www.rcsb.org/pdb/molecules/pdb4_2.html
42
Motors and
Gears
Linear
Moving things, Turn Myosin grabs
shafts, move along actin filaments
and pulls.
lines in step-wise
fashion
Motors
Dynein and
kinesin crawls
along
microtubules.
Kinesin goes out
to membrane
and dynein goes
back.
Molecular "fingers" of stalk are able to grab hold of tubes.
1. http://www.stir.ac.uk/departments/naturalsciences/DBMS/
coursenotes/30CB/KINESINS1.html
Rotates cilia and
Motors and flagella
Gears
Bacterial
flagella protein
Rotary
Protein dynein moves microtubules.
Motors
http://www.bmb.leeds.ac.uk/illingworth/motor01/#dynein
Move fluids and
Pumps
Membrane
ions from one side
channel
of a membrane to
proteins,
another.
e.g.potassiumsodium pump
The protein pump (brown) is shaped to let one ion, sodium, go
through.
Joiners,
hinges
Make compounds;
Hold workpieces
Enzymes
e.g., aldosase,
an enzyme
and clamps
Aldosase - NIH The active site of the enzyme aldosase joins
43
two molecules, red and yellow here, together in a cradle so
they can bond.
Assists movement, Serpin, helps
Chaperones structures
the triple helix
development,
collagen
enzymatic action
fold.(See
by shielding
above.)
molecules from
charges of other
molecules.
Some scientists think the kind of "cradle" of red beta sheets
helps the serpin hold onto the collagen strands.
Carries molecules,
Hemoglobin
Hemoglobin is made of 4 protein
Holders and usually with the
holds and
Transporters help of a metal, to transports
(green), a kind of platter that carries
where they are
oxygen to where
the oxygen.
needed.
it is needed.
Cutters
Cut into pieces
strands, each of which holds a heme
Enzymes
e.g. lysosyme
The active site of the enzyme lysosyme breaks a molecule into
several pieces. www.sci.sdsu.edu
Identify
Decoders molecular
The 'stalk" or barrel of an antibody
holds on firmly while two "hands"
fragments identify specific molecules.
44
Worksheet #2 lesson plan 4
MUTATIONS WORKSHEET (student)
A mutation is a change in the nucleotide sequence of DNA. Mutations can involve large regions of the DNA or just a
single nucleotide. How can small changes, such as altering a single nucleotide in the DNA sequence, cause such big
changes in the phenotype, as the disease of Sickle Cell Anemia? In this activity we will be exploring several kinds
of mutations.
A. Substitutions
1. Open and run the Molecular Workbench model: Mutations: Substitutions and Deletions.
1. From your browser. Click the link below.:
* Molecular Workbench: Mutations
[http://xeon.concord.org:8080/modeler/webstart/protein/mutations.jnlp]
2. By going through the Molecular Workbench application on your computer (workbench.jar) . Then you should click
the following links: Student Pages, Protein Folding, Mutations or Hemoglobin.
It may take a short while to launch the Molecular Workbench the first time.
2. Run the model and note the "flying bird" pattern (Arg-Ser-Gly-GLy-Gly-Ala-Gly-Gly-Gly-Arg-Gly-Gly-Gly-Sergly-Ala-Gly-Gly-Ala-Glu,
which also can be written as:
R-S-G-G-G-A-G-G-G-R-G-G-G-S-G-A-G-G-A-E) because scientists recently began using a one letter code for amino
acids.So Arginine (or Arg) can be also coded with letter R; Serine with letter S, or Glycine with letter G, etc.
3. "Mutate" the genetic code for the bird-like protein. Go to the DNA section below the model, where the
nucleotides are arranged in groups of three. Count over three codons. Substitute the G of the third codon (GGA) in
DNA to A, making the codon AGA. * Remember to make the mutation by changing the DNA, not the amino acids.
Click "Run." Describe what happens, if anything, to the shape of the bird.
45
4. Now make three changes in the sequence of DNA by randomly substituting (replacing) any of the nucleotides
with another. (The last codon is an interesting one to change. ) Record what nucleotide you changed (for example,
"In the fifth codon, I substituted the first nucleotide A to the nucleotide T") and describe below how the
replacement affected, if at all, the shape of the protein.
a.
b.
c.
5. Explain why some substitutions of nucleotides in the DNA appear to have no effect on the protein and some have
great effect.
B. Deletions.
1. Scroll to the bottom of the page.
2. Click the link to the Deletion Challenge.
3. Change the same sequence of DNA by deleting the whole third nucleotide. Click "Run."
4. Describe what happens to the shape of the protein.
5. The following is a list of the original amino acid sequence.
Arg-Ser-Gly-Gly-Gly-Ala-Gly-Gly-Gly-Arg-Gly-Gly-Gly-ser-Gly-Arg-Gly-Gly-Arg-Glu
(R-S-G-G-G-A-G-G-G-R-G-G-G-S-R-G-G-A-E)
Record the new protein sequence below.
6. Describe how the DNA code changed after you deleted the third nucleotide? (You may want to reset the model
by clicking the "reload page" button in the menu bar.)
46
C. Comparison of Mutations.
Which type of mutation has the greater effect, substituting a nucleotide or deleting one? What might explain this
difference?
WORKSHEET #3 Lesson Plan 4
Protein Malfunction and Disease: Making a Sickle Cell Mutation
(Student version)
Scientist know that Sickle Cell Disease is an example of a disorder caused by mutation in the DNA. The result of
the mutation is a misshaped protein that includes a replacement of a hydrophilic glutamic acid (E) for hydrophobic
valine (V). In this activity you will look at the amino acid change and determine the molecular basis for the disease
that lies in the DNA. You will then be asked to relate the change in the protein to the implications for the health
of the individual that has the mutation.
The molecular defect that causes Sickle Cell Anemia can be only ONE amino acid, although the full hemoglobin
complex is over 574 amino acids long! You can model the effect of one amino acid change by making the critical
piece of hemoglobin.
A model of the critical hemoglobin fragment in the red blood cell of a normal person.
1. Open the Molecular Workbench:Hemoglobin
The model can be opened in one of two ways:
1. From your browser. Click the link below.:
* Molecular Workbench: Hemoglobin
[http://xeon.concord.org:8080/modeler/webstart/protein/hemoglobin.jnlp]
2. By going through the Molecular Workbench application on your computer (workbench.jar). Then you should click
the following links: Student Pages, Protein Folding, Mutations or Hemoglobin.
It may take a short while to launch the Molecular Workbench the first time.
2. Build a string, modeling the hemoglobin fragment of a normal person with the following amino acids: (remember
to change amino acids and you are using a windows machine you do control +right click on an amino acid or on a
Macintosh control+apple+click on the amino acid to change it)
The amino acid list is: Valine-Histadine-Leucine-Threonine-Proline-Glutamic Acid-Glutamic Acid-Lysine-SerineAlanine-Valine-Threonine-Alanine-Leucine-Tryptophan-Glycine-Lysine-Valine-Asparagine-Valine
This is part of the code that is usually in every hemoglobin in our body. You miight want to work with another
student to make sure you get the right sequence.
47
Write down the DNA codon for the sixth amino acid., Glutamic Acid.
3. Run the model and draw and describe the shape.
4.. Build a model of the critical hemoglobin fragment from someone with Sickle Cell Anemia by clicking on the
sixth amino acid from the left, the Glutamic Acid, and replacing it with Valine.
Write down the DNA codon for the sixth amino acid., Glutamic Acid.
5. Draw a pictureof the shape of the chain in the space below. There should be a more pronounced "bump" in the
shape, though this might be hard to see, as computers sometimes vary.
When the codon for the wrong amino acid makes a section of protein shape more like a "bump", the whole
hemoglobin gets distorted. The "bump" fits into other hemoglobin and they get held together in long strings that
stretch the cells into a sickle shape.
48
worksheet #4- Lesson Plan4
A Geometric Story of Sickled Hemoglobin
Direction: Use pencil and protractor. Trace the different figures of hemoglobin and other proteins as to
their geometric angles and shape. Label these figures as to the steps on how sickle cell develop.
Summarize the story by using the geometric figure you created. Use an arrow every after the figure.
( Note: use only the figure to summarize the story
1. In every red blood cell there are 280 million molecules of hemoglobin, a critical protein. Read a few pages
introducing hemoglobin.
http://www.concord.org/~barbara/homs_workbench/blood2.html
2. Hemoglobin protein is a long twisted strand of amino acids, altogether carefully cradling a
heme, a disk whose iron in the center attracts, carries and releases oxygen.
Image: Dickerson p. 16
3.One hemoglobin is made of 4 protein protein chains, or globins, Two strands are
"alpha" chains, and two are "beta" strands. The 4 strands assemble together so that,
like a ball glove, it can carry oxygen. When assembled, a normal hemoglobin has
indentations in the strands. It is completely surrounded by water molecules.
Image: Dickerson p.17
4. In sickle cell valine is substituted for glutamic acid in both beta chains. This changes the shape of
the protein: a small protrusion (or dent?) appears on the surface of the proteins.
Image: http://rad.usuhs.mil/sickle/index.
49
5. This bump fits exactly into the existing "pocket" on the surface of the next protein. The two
proteins "clump" together, then the third clumps...This creates a kind of domino effect, leading to the
formation of long fibers made of many millions of damaged hemoglobin molecules. (polymerization) This
seems to happen when the hemoglobin does not have its oxygen. The hemoglobin loses its solubility and
clumps into bundles. (Scientists are working on making the hemoglobin of Sickle Cell patients more
soluble.
Image: http://rad.usuhs.mil/sickle/index.
6. The long bundled hemoglobin twist in a regular fashion.
7. These bundles self associate into even larger structures that stretch and distort the cell into a sickle shape.
8. The long fibers distend the cell.
9. The sickled cells clog the capillaries, thereby delivering less oxygen and causing pain.
Summary:
50
Worksheet # 5 Lesson Plan 4
How to create a vodcast
Steps for offering video on demand
by Christopher Breen, Playlist Magazine Jul 26, 2005 3:00 am
Podcasts are so last month. If you want to get in on the hip trip, you’ll turn your attention (and camcorder) to
vodcasts—Video-On-Demand-casts, that is. No, this isn’t stuff of the future. By following the steps I’m about
to outline you can create and distribute a downloadable vodcast today.
Similar Articles:

How to make a photo journal in iPhoto

Four favorite tips for green computing

How to print multiple images on a single page
51

Canon imageFormula P-150

Printing primer: Know your options in Adobe InCopy

US peer-to-peer traffic lower than world average
The technology behind vodcasting is the same as the magic that makes up podcasting—RSS. By preparing your
movies properly and creating the right feed, you can offer your audience video on demand through an
application familiar to us all: iTunes 4.9, a version of iTunes that supports playback of local and streamed
video. Here’s how to go about creating and distributing a vodcast of your own.
Tools You’ll Need:



Some kind of server connected to the Internet (this can be your iDisk, although the faster and more sustainable
the server connection, the better).
A website for hosting the XML file that allows iTunes access to your video.
QuickTime Pro 7 (for encoding your video in a format such as H.264)
Step 1: Create a movie
Vodcasting is nothing without video. Use a video application such as iMovie or one of the Final Cuts to create
your movie. To get great looking video at a smallish size, use the program’s Export command to save the movie
in H.264 format.
52
Step 2: Compress the movie
Open the movie in QuickTime Player Pro 7. Choose Export from the File menu and in the resulting Save
Exported File As dialog box, choose Movie to MPEG-4 from the Export pop-up menu. Click the Options button
and in the MP4 Export Settings window that appears, choose MP4 from the File Format pop-up menu. In the
Video Format pop-up menu select H.264. To keep file size smaller, select a modest image size (say 240 x 180)
and a frame rate of 15 fps. (Of course, if you’re delivering a small file to begin with, feel free to increase the
image size and frame rate.)
Click the Audio tab and make sure that AAC-LC (Music) is selected in the Audio Format pop-up menu and
choose a modest data rate from that pop-up menu (48 kbps, for example). You’ll save even more space if you
choose Mono from the Channels pop-up menu and an output sample rate of 32.000 kHz.
Click the Streaming tab and enable the Enable Streaming option. Click OK to dismiss the window and click
Save in the Save Exported File As window to compress your video. Compessing the movie could take quite a
while if it’s long and large.
Step 3: Put it on the server
Mount the server from which the movie will be delivered and place the compressed movie file in a download
directory for your website—for example, ~/Library/WebServer/Documents/yoursitename where yoursitename
is the name of, well, the website that will deliver your content.
If you don’t have a server, you can use your iDisk. To do so, mount your iDisk and place the movie file in the
Sites folder.
Step 4: Create the XML file
The XML file you create will allow iTunes to access your movie. In the text box below you’ll find an example
file to get you started. Simply copy the code from the box below, paste it into a plain text TextEdit document,
replace the example entries with entries that match your needs (for example, Your Movie Title should be
replaced with the real title of your movie), save the file with the .xml extension— myvodcast.xml , for
example—and you’re good to go.
Note that you’ll need to fill in the length of your movie in the itunes:duration area of the xml file. To learn the
length of your movie, open it in QuickTime Player and drag the playback bar to the end of the movie and look
at the timecode readout. Enter this number in hours:minutes:seconds—01:12:32 for 1 hour, 12 minutes, and 32
seconds, for example. You may also want to add keywords so that those creatures that prowl the web can more
easily index the content of your movie.
If you’d like to point to additional vodcasts to the file, copy the lines of code between the ITEM and /ITEM
entries and paste them before the line of code that reads /CHANNEL.
Step 5: Place the XML file
Place the completed XML file in the same directory as your movie(s). If you’re using your iDisk, place the
XML file in the Sites folder.
53
Step 6: Test in your browser
Launch your browser and enter the address to your XML file in this form:
http://www.yoursitename.com/yourvodcast.xml. A page should appear that lists the title of your vodcast at the
top along with a Read More link that, when clicked, takes you to a page where you can view your movie. The
URL in the Address field should have changed so that feed replaces http , as in:
feed://www.yoursitename.com/yourvodcast.
Step 7: Check it in iTunes
Launch iTunes 4.9 and select Subscribe to Podcast from the Advanced menu. Enter a URL along these lines:
http://www.yoursitename.com/vodcast.xml where yoursitename is the name of your website and vodcast.xml is
the name of your vodcast’s XML file—http://www.example.com/coolcast.xml, for example. If you’re doing this
via iDisk, you’d type something like http://homepage.mac.com/example1/coolcast.xml.
When you enter this URL in the Subscribe to Podcast window and then click OK, an entry for the vodcast will
appear in the Podcast playlist within iTunes’ main window and the video will begin downloading to your
computer. Click the Play button and the video plays in the small video window in the lower left corner of the
iTunes window. Click on this window and the video appears in a larger, separate window. Control-click (Mac)
or Right-click (Windows) on this window and choose Full Screen to view the video at full screen.
Step 8: Let the world know
Send the link to your vodcast to your nearest, dearest, colleagues, contacts, and those you simply wish to make
jealous and instruct them to enter that URL in the Subscribe to Podcasts window to view your work. Your video
will appear in iTunes’ Podcasts area.
Important note: Video files are generally quite large and delivering a popular vodcast is going to burn up a
load of bandwidth. Before going into the vodcast business, find a way to fund the bandwidth necessary to
deliver your movies.
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Reference: Reference: http://www.teach-nology.com/web_tools/rubrics/presentation/
RUBRICS
You must consider each category below while completing your report.
PODCASTING PRESENTATION
Name: ________________________
Teacher:
Date of Presentation: ____________
Title of Work: ___________________
Criteria
1
2
Points
3
Audience cannot
Audience has
Student presents
understand
difficulty following information in
presentation
logical sequence
Organization presentation because
there is no sequence of because student
which audience
information.
jumps around.
can follow.
Content
Knowledge
Student is
Student does not have
uncomfortable with
grasp of information;
Student is at ease
information and is
student cannot answer
with content, but
able to answer only
questions about
fails to elaborate.
rudimentary
subject.
questions.
Student used no
visuals.
Visuals
Mechanics
Delivery
Student occasional
Visuals related to
used visuals that
text and
rarely support text
presentation.
and presentation.
4
Student presents
information in
logical, interesting
sequence which
audience can
follow.
Student
demonstrates full
knowledge (more
than required)with
explanations and
elaboration.
Student used
visuals to
reinforce screen
text and
presentation.
Presentation has
Student's presentation Presentation had no more than two Presentation has
had four or more
three misspellings
misspellings no misspellings or
spelling errors and/or and/or grammatical
and/or
grammatical
grammatical errors.
errors.
grammatical
errors.
errors.
Student mumbles, Student incorrectly
Student used a
incorrectly pronounces pronounces terms. Student's voice is
clear voice and
terms, and speaks too Audience members clear. Student
correct, precise
quietly for students in have difficulty
pronounces most
pronunciation of
the back of class to
hearing
words correctly.
terms.
hear.
presentation.
Total---->
____
____
____
____
____
____
Teacher Comments:
Powered by TeAch-nology.com- The Web Portal For Educators! (www.teach-nology.com)
55
RUBRICS
You must consider each category below while completing your report.
ORAL PRESENTATION
Name: ________________________
Teacher:
Date of Presentation: ____________
Title of Work: ___________________
Criteria
1
2
Points
3
Audience cannot
Audience has
Student presents
understand
difficulty following information in
presentation
logical sequence
Organization presentation because
there is no sequence of because student
which audience
information.
jumps around.
can follow.
Content
Knowledge
Visuals
Mechanics
Delivery
Student is
Student does not have
uncomfortable with
grasp of information;
Student is at ease
information and is
student cannot answer
with content, but
able to answer only
questions about
fails to elaborate.
rudimentary
subject.
questions.
Student used no
visuals.
Student occasional
Visuals related to
used visuals that
text and
rarely support text
presentation.
and presentation.
4
Student presents
information in
logical, interesting
sequence which
audience can
follow.
Student
demonstrates full
knowledge (more
than required)with
explanations and
elaboration.
Student used
visuals to
reinforce screen
text and
presentation.
Presentation has
Student's presentation Presentation had no more than two Presentation has
had four or more
three misspellings
misspellings no misspellings or
spelling errors and/or and/or grammatical
and/or
grammatical
grammatical errors.
errors.
grammatical
errors.
errors.
Student mumbles, Student incorrectly
Student used a
incorrectly pronounces pronounces terms. Student's voice is
clear voice and
terms, and speaks too Audience members clear. Student
correct, precise
quietly for students in have difficulty
pronounces most
pronunciation of
the back of class to
hearing
words correctly.
terms.
hear.
presentation.
Total---->
____
____
____
____
____
____
Teacher’s comments ____________________________________________________________
Powered by TeAch-nology.com- The Web Portal For Educators! (www.teach-nology.com)
Reference: http://www.teach-nology.com/web_tools/rubrics/presentation/
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