Download Three Full Blocks And Partial Time In Two Additional Blocks

Biology Lesson Plan
GENA Workshop - 2009 Cohort
Denay Gray (North High School, Des Moines, Iowa)
Heidi Sleister (Drake University, Des Moines, Iowa)
Dates: May 6-19, 2010 - three full blocks and partial time in two additional blocks
National Standards:
1. Cells store and use information to guide their functions. The genetic information stored in
DNA is used to direct the synthesis of the thousands of proteins that each cell requires.
2. In all organisms, the instructions for specifying the characteristics of the organism are
carried in DNA, a large polymer formed from subunits of four kinds (A, G, C, and T). The
chemical and structural properties of DNA explain how the genetic information that
underlies heredity is both encoded in genes (as a string of molecular “letters”) and
replicated (by a templating mechanism). Each DNA molecule in a cell forms a single
chromosome.
3. Most of the cells in a human contain two copies of each of 22 different chromosomes. In
addition, there is a pair of chromosomes that determines sex: a female contains two X
chromosomes and a male contains one X and one Y chromosome. Transmission of genetic
information to offspring occurs through egg and sperm cells that contain only one
representative from each chromosome pair. An egg and a sperm unite to form a new
individual. The fact that the human body is formed from cells that contain two copies of
each chromosome- and therefore two copies of each gene- explains many features of
human heredity, such as how variations that are hidden in one generation can be
expressed in the next.
4. Changes in DNA (mutations) occur spontaneously at low rates. Some of these changes
make no difference to the organism, whereas others can change cells and organisms. Only
mutations in germ cells can create the variation that changes an organism’s offspring.
Objectives: Students will be able to:
1. Generate a list of symptoms that would classify sickle cell disease and make
judgments about how to diagnose this disease.
2. View and Compare the structure and shape of normal RBC and sickled red blood cells.
3. Conclude on how and why a change in RBC can affect blood flow and result in sickle
cell disease symptoms.
4. Draw and Analyze a pedigree from a description of a family in which some members
are affected by sickle cell anemia.
a. Identify correctly the mode of inheritance in the pedigree (autosomal recessive).
b. Accurately calculate the expected frequency of which two heterozygotes could
produce an affected child.
5. Compare DNA sequence of the wild-type (WT) and mutant (HbS) alleles of the hemoglobin gene, identify the mutation present and describe the difference found.
6. Virtually transcribe and translate a portion of DNA derived from the normal (HbA)
and mutant (HbS) -hemoglobin alleles and identify both missense and silent
mutations using a genetic code chart.
7. Describe and identify mutations using correct vocabulary.
8. Explain the relationship between genotype and phenotype with respect to sickle cell
anemia.
Student Misconceptions Addressed:
1. All mutations are harmful.
a. We will compare and contrast the effects of missense and silent mutations in the hemoglobin gene. Homozygosity of the missense mutation (Glu6Val) causes sickle cell
anemia. In contrast, the silent mutation Glu6Glu is not expected to alter an individual’s
phenotype (i.e., not harmful).
2. Students fail to connect that phenotypes are controlled by proteins (rather than DNA).
a. We will correlate a disease phenotype (sickle cell anemia) with a defective protein that’s
encoded by a mutant gene. The defective protein aggregates and forms long fibers
which cause red blood cells to sickle. This leads to the disease phenotype.
3. Sickle cell anemia only affects African Americans.
a. We will compare the frequencies of individuals with sickle cell anemia in different
populations to show that while sickle cell anemia may be more prevalent in some ethnic
groups, it is found across ethnic groups.
4. A mutation in a gene will always change the amino acid sequence of the gene product.
a. We will compare and contrast the effects of missense and silent mutations in the hemoglobin gene. In the case of the silent mutation, the amino acid sequence is not
altered.
5. An individual has sickle cell anemia (disease) because they have the sickle cell gene.
a. We will reinforce the concept that everyone has two copies (alleles) of the -hemoglobin
gene, but a person with sickle cell anemia has two defective (HbS) alleles.
6. Genes and chromosomes are synonyms.
a. Students will learn that the hemoglobin gene is located on an autosome
(chromosome 11), and since each individual has two copies of chromosome 11
(homologs), they have two alleles for this gene. If the alleles are identical, the person is
a homozygote; if the alleles are different, the person is heterozygote.
7. A phenotype results from the normal expression of a gene. A phenotype is not just the
normal expression of a gene. Any expression of a gene is the phenotype- normal or mutated.
a. Students will learn that a phenotype can result from both the normal expression of a
gene and from the expression (or lack of expression) of a mutated gene. .
Lesson:
May 6-7 – 20-25 minutes
**PRETEST - Administer a PRETEST to students to determine existing accurate knowledge
and identify misconceptions of the concepts to be covered: chromosome structure, patterns of
inheritance as displayed by a pedigree, transcription and translation, presence of mutations in
genetic sequences, mechanisms and products of gene expression at the molecular level,
classifications of mutations, gene mutation effects on phenotypes, function of the RBC and hemoglobin. Hand out tests, students complete and turn in.
May 10-11 – Full Block (90-95 min)
1. ENGAGEMENT (E1) Mystery of the Crooked Cell Stations.
Adapted from Mystery of the Crooked Cell: An Investigation & Laboratory Activity about
Sickle-Cell Anemia Author(s): Donald A. DeRosa and B. Leslie Wolfe Source: The American
Biology Teacher, Vol. 61, No. 2 (Feb., 1999), pp. 137-148 Published by: National Association
of Biology Teachers http://www.jstor.org/stable/4450635
Introduction: Sickle Cell Patient Scenario (10-15 min): Hand out sickle cell patient
scenario reading to students. Using highlighters, have students individually mark information
from the reading that they think would be useful clues to the diagnosis of the patient’s disease.
As a class, compile a list of the information gathered and discuss the results. ASK: What types
of tests do you think the physician could do to determine what disease these
symptoms represent? List and discuss class answers. (Ideally, students will come to
determine that a blood test would be beneficial in diagnosing a disease. This will lead to
activities in which students view red blood cell pictures and model blood flow in a “normal”
individual and a person with sickle cell anemia.)
REFLECTION:
We handed out to each student a ½ sheet of the reading which was glued into their lab notebooks. We noticed
that it would be a good idea in the future to remove the caption from the bottom of the sheet which noted the
source of the material, as it gave away the name of the disease earlier than we had intended. This activity was
definitely a good engagement tool, as students were very interested to find out more about what caused the
symptoms! The class discussions of diagnosis information drawn from the reading and lists of possible tests
were widely participated by many students. We were also very happy to find that in every class, the BLOOD
test was the first to be suggested, as we observed that many students had this written in their books. Other
suggestions included liver, physical, eye, digestive tests and the like. In the future, we would add in a
component in which students would give a brief justification for their test choices—i.e. a respiratory test would
be useful to determine the cause of the shortness of breath.
*Using directions modified from the Mystery of the Crooked Cell paper, students will work
through two stations to determine the phenotypes of blood cells and blood flow associated
with sickle cell anemia. These two stations allow students to use an inquiry-based approach
to construct a connection between the RBC (Red Blood Cell) structure of normal and SC
(Sickle Cell) varieties and the symptoms of sickle cell disease that can result.
Students will work in pairs. Half the class can start with Station 1; the other half can start
with Station 2.
o Station 1: Normal v. Sickled Red Blood Cell ImageViewing (15 min)
Handout includes: pictures of microscope slides with RBCs from a normal individual and a
person with sickle cell anemia, analysis questions (making observations about each slide and
comparing/contrasting the two, make a judgment about which slide contains the most cells and
why a person would be negatively affected to have fewer red blood cells in their blood).
REFLECTION:
For this first station, it would be most ideal to have microscope slides of normal and sickled RBC, since the
students really like hands on activities. However, we found that the ones we had available were not of good
quality and so substituted pictures of RBCs instead. This worked well enough, but for next year, we are going
to have actual slides or at least colored RBC pictures instead of black and white. A possible variation would be
to have the students draw the cells from the colored pictures (if that is again an option) rather than simply
analyze the pictures provided—more hands on. Also, we would change the wording on this lab sheet to refer
to the sickled blood cells as “diseased’ cells, as it again gives away the name of the disease before we
intended.
o Station 2: Tube Capillary and Clay Red Blood Cells Model (15 min)
Handout includes: place to draw, color and label the two tube/clay cell scenarios as presented in
the modeling directions. Analysis requires students to identify what the clay cells and tube are
models for in the body and explain how misshapen cells can change the flow of blood. What
symptoms do you think would result in a person with this change in blood flow?
 Sickle-shaped red blood cells can clump together and block capillaries, tiny blood
vessels. This prevents adequate delivery of oxygen to tissues and can result in pain,
infections, fatigue, and organ damage.
REFLECTION:
This activity worked GREAT to show how sickled cells occlude the flow of blood in capillaries. The students were
engaged and enjoyed trying out the different cell flow scenarios and observing and recording the results. This
activity did, as we had hoped, create a connection between the patient scenario and the phenotype of normal vs.
misshapen cells. A change we would make would be to ask students to make PREDICTIONS to the flow of blood
cells through the tube BEFORE they attempt it—many students seems intrigued that the sickled cells were getting
stuck in the tubes, even in combination with rounded cells.
Station 2 Pictures:
*Once student groups have completed both stations, make a T-chart on elmo and ask
students to contribute to compiling a list of observations from each station; then work
together to come up with the two concluding concepts listed below. What did each of the
stations teach them about how the disease works? What causes the symptoms of this
disease? If students have not yet determined the name of the disease, discuss
here—ask them what they think it should be called.
Conclusion concepts: 1. The blood cells are irregularly shaped and vary in quantity. 2. The
irregular shape of the RBCs interferes with their ability to flow through the blood pathways.
These two concluding concepts can then be referenced back to the opening Patient Scenario to
determine that the symptoms described therein are a result of this disease.
REFLECTION:
PRIOR to the above conclusion discussion of the stations, several students asked, unprompted: “How do your
cells get like that?” referring the sickle shape of the RBCs. HOORAY for inquiry!!
(E1 cont) Sickle Cell Disease – Video (5 min) http://www.webmd.com/video/sickle-cellmiracle Using laptop and infocus machine, show students this ~3 min video which briefly
introduces the disease of Sickle Cell Anemia in the context of the life of a teenage AfricanAmerican boy. http://www.webmd.com/help/video-help# (for trouble with video pausing while playing)
REFLECTION:
This three minute video was well worth including in this lesson. Many students verbally referred back to this
very short clip several times in subsequent lesson segments. It does a good job of showcasing the phenotype of
the disease and the symptoms associated with it without giving away the molecular basis of the genetics for the
disease. Download video on disk to avoid internet glitches.
o
Then, ASK: What causes the RBC to be misshapen which adversely affects the
function of these cells? (Put this question up on the screen.) Students will be handed
sticky notes on which to record their answers to this question (completed
INDEPENDENTLY). Students will write names and blocks on their sticky note, and all
will be collected. These will be addressed later in the lesson as part of a formative
assessment.
REFLECTION:
Responses to this question ranged widely, however, in each class, there were a few students who inferred that
the diseased cells were caused by a mutation of some sort. HOORAY!!
May 12-13 – Full Class Block
2. EXPLORATION (E2) Part #1 Sickle Cell Disease Pedigree Analysis (30-40 min)
ASK: How do you think people get sickle cell disease? Inherited How would you figure out
how a person inherited a disease? Pedigree analysis. Students will complete a pedigree
analysis example of the inheritance of Sickle Cell Disease. Using the written description
provided, draw and correctly label the corresponding pedigree with appropriate notations
and genotypes, then answer the questions attached. Students will be provided an individual
copy of this activity for their lab notebook.
o Pedigree description: Joe and Jackie have four children and are expecting a baby.
Two of their children (Angie and Bob) have sickle cell anemia, and their other two
children (Carl and Debbie) do not have the disorder. Joe’s parents, Jackie’s Dad, and
Jackie’s sister do not have the disorder. However, Joe’s brother has sickle cell
anemia, and Jackie’s mom had the disorder and died as a young woman. Joe and
Jackie ask you, a genetic counselor, how this disorder is inherited (dominant or
recessive) and what the likelihood is that their unborn child will have sickle cell
anemia.
o Analysis Questions: Based upon the pattern of inheritance shown in the pedigree you drew,
answer the following questions.
1. Is this disease dominant or recessive?
2. Explain how Bob can have the disease if neither of his parents have the disease.
3. What would be the correct genetic term to describe the genotype of Bob’s unaffected
parents?
4. What is the probability that Bob’s parents would have a 5th child (represented as diamond
in pedigree) with sickle cell anemia? SHOW YOUR WORK with a Punnett Square.
5. If Bob married and had a child with a woman who is homozygous for the normal allele,
what would be the probability that the child would have sickle cell disease? What is the
probability that the child would be a carrier? SHOW YOUR WORK with Punnett Squares.
REFLECTION:
The analysis questions presented above are a little different from the ones that we used on the actual handout
in class, but it seemed to us that any of the questions from either source would be appropriate with this
pedigree activity, based upon the students’ previous work. Students worked on this activity individually, and
then the class shared information to construct the correct completed pedigree together. Add in information
regarding the use of diamonds on pedigrees—this was new information for my students.
Review/discuss the relationship between CELL/CHROMOSOME/GENE/DNA.
(5 min) Students will have already learned this concept and will have reviewed in multiple
times in previous classes. So, teacher will lead a brief discussion in which students will recall
that chromosomes are made of many 100s or 1000s of genes and each gene is a segment of
DNA which codes for the production of a particular protein which, in turn, controls (all or in
part) some aspect of an individual’s phenotype.
REFLECTION:
Originally, we had intended to review this concept with previously used teaching materials and a sticky note
formative assessment, but since students had repeatedly reviewed this material in the weeks prior to this lesson
as a part of related topics in meiosis and genetics, it was reasonable to scale down this segment to a more
simple version.
Geneticist Introduction of Molecular Basis for Sickle Cell Anemia – Heidi introduced
the class to the chromosome on which the gene for beta-hemoglobin resides (the mutated
version of which causes SCA) by showing a short slide show which included:
 Review of the structure of normal and sickled blood cells and their differing functions in
the flow of blood through capillaries.
 Discussion of the function of hemoglobin in the transport of oxygen.
 A picture of chromosome 11—including HBB (hemoglobin beta) locus.
REFLECTION:
This is the portion of the lesson where the students begin to investigate the cause of the sickle cell disease at the
MOLECULAR level. This was also the first segment of our lessons in which Heidi led the class—it was wonderful
to see how receptive the students were to her presence in class and they participated in the discussions easily
with her.
3. EXPLORATION (E2) Part #2 HBB (hemoglobin beta) DNA Sequence Analysis
(30 min) Students will work individually for this activity. Each student will be provided a
handout with two versions of the DNA base pair sequence of the HBB gene – one will be the
wild-type sequence (normal) and the other will be mutant (HbS). Students are to compare
the two sequences and circle the difference on the HbS sequence. Once the mutation is
found, students are to complete the transcription/translation activity that accompanies for
both gene sequences and answer the questions that follow. This activity will be attached
and retained in the lab notebook.
o Mutation of the DNA corresponding to the 6th codon (GAG to GTG) results in a
Glutamate to Valine change at amino acid 6. This is a missense mutation.
REFLECTION:
This was another situation in which we adjusted the 4-5 analysis questions for the product used in class from the
original version sent in our draft lesson. Again, we feel that either version of these questions is appropriate,
depending on the progress of the class and the methods of teaching. In carrying out this activity with the
students, it was apparent that it would have been a good idea to do the first base triplet/codon/AA sequence
together. All classes had learned protein synthesis in the weeks prior to this lesson and while many students
were able to start independently, there were also many that needed a brief and direct refresher to continue on
their own. Additionally, we discovered that some of our terminology was not aligned in referencing the strands
of DNA, mRNA and polypeptides----I had not used the terms RNA-like strand with the students, nor did I refer to
the ends of the polypeptide as N-C. For next year, I will use these terms with the students in the lessons on DNA
replication and protein synthesis so as to better prepare them for this applied activity. In terms of formatting, we
found that it would have been a good idea to separate the codes into groups of 3 with backslashes (/) to help
students keep the data in line or we could have draw in vertical lines to achieve the same result. It would have
also been helpful to lightly shade over or box in the template strand of DNA to strongly identify it as the strand
used to generate mRNA and ultimately the polypeptide.
After this sequencing activity was completed, a few students in different classes, asked: So, when we had to do
that sticky note thing and explain the shape of the blood cells, is this what you were asking about? WOW, what a
connection! Indeed it is what we were asking about! We felt that these types of questions showed that the
engagement was still going strong with many students to find out more about how SCA is caused.
4. EXPLANATION (E3) Geneticist PowerPoint Lecture: (20-30 min) This is the
portion of the lesson in which Heidi presents an explanation to the class regarding the
nature of mutations, different types of mutations (including the correct names and examples
of each) and how this mutation information relates to the study on Sickle Cell Disease at the
molecular and genetic level.
o Hemoglobin in the Cell Models w/balloons and pop beads. (Refer back to the
Mystery of the Crooked Cell article for directions regarding this demo. The paper does it
as a student station, we were going to use it as a teacher model during PPT lecture.)
Conclusion: The -hemoglobin proteins produced by the HbS allele aggregate together
when oxygen concentrations in the blood are low, resulting in abnormally shaped (sickle)
red blood cells.
REFLECTION:
We found that the balloon and pop-bead models worked GREAT to
show how the aggregated hemoglobin proteins from the HbS alleles
form a sickled shaped cell in the phenotype of individuals with a
homozygous recessive genotype! We also agreed that it might have
been advantageous for students to have learned about karyotypes
before this presentation as, up to this point, students had mostly
worked with chromosomes individually or in a small number of
pairs. Students did seem to grasp easily the genotypes of normal
and affected individuals in relation to this gene and the resulting
phenotypes. It was pleasing to have students apply their genetics
knowledge to an example in context!
May 14-17 – Full Class Block
PowerPoint Presentation Review Questions: hand out to students a half sheet of
questions that reviews information presented in the PPT by Heidi last block. Allow students
about 5-10 minutes to independently and collaboratively answer as many of the questions
presented that they can. Then review each by discussion and revisiting the powerpoint slides
which are applicable.
REFLECTION:
We realized during the Explanation PowerPoint that students had no means of taking notes or recording
information. So, at the beginning of the next block, I handed out a sheet of short review questions and
proceeded as the directions above. In all classes, it was necessary to go back to the slide show to review some of
the more technical and new information. This worked out fine as it was an opportunity to discuss the material
further.
5. EVALUATION (E5) – Lesson evaluation takes the following forms:
a. Sticky notes revisited: After watching the video early in the lesson, students were
asked to write an answer to the question: What causes the RBC to be misshapen
which adversely affects the function of these cells? These sticky notes will be
redistributed to the students and they will evaluate their answers. During this time,
students will be asked to complete a new sticky note that answers the same question
using the newly acquired information of the past two lessons to do so. Both sticky notes
will be recollected.
REFLECTION:
It is useful to be able to separate the first and second sticky note responses. We did this by having students add
the date to their papers, but better yet would be to use two different colors of sticky notes (one color for each
of the different responses).
b. Post test – Students will take the pre-test again as a post test but with additional
questions specifically related to sickle cell disease and the HBB gene. Their scores will be
compared.
c. DNA Sequence Assessment: Based upon their work in Exploration Part #2 of the
lesson, students will be provided another pair of DNA sequences to compare (wild-type
HbA allele and HbX allele). The HbX allele contains a silent mutation at codon 6 (GAG
to GAA, and this does not alter amino acid 6. Since the original and mutated codon both
specify glutamate, this is a silent mutation). Students will proceed in the same manner
as previous—locating and indentifying the mutation, transcribing and translating the
sequence and making a judgment about how this mutation will affect the phenotype of
the individual. This activity will be collected and graded and therefore, will be completed
individually.
REFLECTION:
An error on the DNA Sequence Assessment did not result in the students finding a silent mutation, but still the
assessment was quite useful as a way to determine students’ mastery of transcription and translation and
judging the resulting productivity of the protein produced for the phenotype of the individual.
6. ELABORATION (E4) – Treatments and Natural Selection with Malaria
Interested students will be encouraged to do further independent research on some component
of sickle cell anemia that was introduced during the lesson (e..g, effectiveness of sickle cell
anemia treatments, population genetics in different groups, effect of malaria on population
genetics of sickle cell anemia).
o Prior to post test, have a brief discussion with students regarding population
genetics of sickle cell and how this relates to its connection with malaria (and
evolutionary staying power). Use corresponding PPT slides to aid discussion.
REFLECTION:
Unfortunately, we did not have time to explore too many elaboration avenues for this lesson. It was near to
the end of the school year and I had some other topics earmarked for the remaining lesson days.
GENA Lessons Reflection: A half sheet was provided to students with the following text.
Over the past three blocks we have been working our way through a set of lessons designed in
collaboration with Dr. Sleister, a Drake University genetics professor. Over the course of those
three blocks, we reviewed different concepts learned over the semester (as far back as
January) and applied them to a “big picture concept” of correlating genotype with phenotype
using sickle cell anemia as a focal point. Please take a few minutes and review the materials
we used over these few days from your notebook. We, as your teachers, would very much like
your feedback on those lessons so we can make adjustments for the future. To that end, please
answer the following questions honestly, completely and respectfully. You may put your name
on this paper if you would like, but it is not required. Thank you in advance for your input!!
a. What things did you like best about the lessons on the genotype and phenotype of sickle cell
anemia? Please explain.
b. What parts did you like least about these lessons? Please explain.
c. Write one or two things about sickle cell anemia, genotype, phenotype, etc, that you NOW
clearly understand having worked through these lessons in class.
d. Write any questions you still have.
e. What advice do you have for us from a student’s perspective to make these lessons better?
REFLECTION:
This was a great to finish up our GENA lessons with the students. As I often find with student surveys on curriculum,
many responses were open, respectful, thoughtful and honest. As expected, many students really liked the lab
activities with materials to handle, but surprisingly, several mentioned not liking taking lots of notes (Heidi and I
were perplexed since we didn’t think we offered too many notes!) Overall, the students seemed to enjoy these
lessons and were happy with the new knowledge they had acquired!
Name____________________________
Biology: Genetics – Pre-TEST
Directions: Complete each of the following questions to the best of your ability.
1. Which is SMALLER: a gene or a chromosome? ________________
Explain your answer:
2. Write two pieces of information that you can learn about a person by studying their
pedigree.
a. ________________________________________
b. ________________________________________
Questions #3-8 refer to the pedigree below. Each is to be answered either YES OR NO.
3.
4.
5.
6.
7.
8.
Is the trait represented in this pedigree inherited in an autosomal manner?_______
Is the trait represented in this pedigree x-linked? _______
Is the trait represented in this pedigree dominant? _________
Is the trait represented in this pedigree recessive? _________
Is person III-2 affected? _________
Is person II-2 a carrier?
9. Which of the following molecules provides the master code for the functions carried out by
the cell?
a. DNA
b. mRNA
c. tRNA
d. amino acids
10. Using the template DNA sequence 3’ TTGATAGCACCC 5’, answer the following questions:
a. What would be the corresponding mRNA sequence: ________________
b. How many codons would be in the corresponding mRNA sequence? ______
c. How many amino acids would be determined by this sequence? ______
11. Using the chart below, determine the amino acids that would be coded for by the DNA
sequence above. (write out full names of amino acids)
__________________________________________________________
12. Put an X next to each statement that you think is TRUE. Mark all that apply.
a. DNA molecules are sometimes replicated with changes in the nucleotide sequence.
b. If there is a change in a DNA base sequence, only the DNA molecule is affected.
c. A person’s phenotype is not affected by their genotype.
d. The DNA sequence for a gene would have to have several changes for it to function
improperly.
e. The outcome is always negative (harmful) on an organism when DNA bases are
changed.
f. A phenotype is what you see when a person’s genes are all NORMAL.
g. It is possible for a gene to have a nucleotide sequence change and still function
properly.
h. Some genetic diseases can occur only in one or a few ethnic groups. For example,
sickle cell anemia only affects African Americans.
i. A person who has sickle cell anemia has the sickle cell gene.
j. A person has two copies of each gene located on an autosome.
13. How do you think a cell would behave differently if a part of the DNA sequence was
changed? What molecules would be affected and how would the organism, as a whole, be
different, if at all?
_______________________________________________________________
_______________________________________________________________
_______________________________________________________________
_______________________________________________________________
______________________________________
Crop and glue this sheet into your notebooks
Patient Description
In 1904, Dr. Herrick, a Chicago physician, met a student from the West Indies with a puzzling
condition. Below is a summary of some of Dr. Herrick’s observations. Your job is to learn
more about this condition and to find out how the disease is affecting this patient’s body. To
begin, read the description below and highlight any information you think may be important
for understanding the disease.
Dr. Herrick talked with the patient to learn more about the symptoms he was experiencing.
The patient reported feeling well most of the time. However, he often had fevers and
infections. The patient also reported that while he was young he repeatedly had trouble
breathing. He had pain in the left abdominal area, and this area was tender to the touch. He
also had pain in the joints and muscles in his legs and arms. He reported that he often felt so
weak that he had to rest in bed a few weeks. As an example, one day after a short swim he
became so tired that he could hardly move.
When Dr. Herrick examined the patient, he noticed the whites of his eyes had a yellowish tint.
When Dr. Herrick asked about the patient’s family, he learned that his parents and his two
brothers and three sisters have never experienced these problems. However, his uncle and his
grandmother used to have similar attacks. His grandmother died at a young age.
From DeRosa and Wolfe. (1999). Mystery of the Crooked Cell: An Investigation & Laboratory Activity about
Sickle-Cell Anemia. The American Biology Teacher 61, 137-148.
Crop and glue this sheet into your notebooks
Patient Description
In 1904, Dr. Herrick, a Chicago physician, met a student from the West Indies with a puzzling
condition. Below is a summary of some of Dr. Herrick’s observations. Your job is to learn
more about this condition and to find out how the disease is affecting this patient’s body. To
begin, read the description below and highlight any information you think may be important
for understanding the disease.
Dr. Herrick talked with the patient to learn more about the symptoms he was experiencing.
The patient reported feeling well most of the time. However, he often had fevers and
infections. The patient also reported that while he was young he repeatedly had trouble
breathing. He had pain in the left abdominal area, and this area was tender to the touch. He
also had pain in the joints and muscles in his legs and arms. He reported that he often felt so
weak that he had to rest in bed a few weeks. As an example, one day after a short swim he
became so tired that he could hardly move.
When Dr. Herrick examined the patient, he noticed the whites of his eyes had a yellowish tint.
When Dr. Herrick asked about the patient’s family, he learned that his parents and his two
brothers and three sisters have never experienced these problems. However, his uncle and his
grandmother used to have similar attacks. His grandmother died at a young age.
From DeRosa and Wolfe. (1999). Mystery of the Crooked Cell: An Investigation & Laboratory Activity about
Sickle-Cell Anemia. The American Biology Teacher 61, 137-148.
Crop and Glue into notebook.
Station 1: Red Blood Cell Viewing and Comparing
Directions: Below are images of red blood cells (erythrocytes = erythro-red/cytes-cells) on slides viewed
with a microscope. The picture on the left shows cells from a “normal” individual, whereas the picture on the
right shows cells from a person with sickle cell anemia.
Slides from
http://www.wadsworth.org/
chemheme/heme/microscope
Slide 1: Red blood cells from a
“normal” person
Slide 2: Red blood cells from a
person with sickle cell anemia
Analysis: Answer the questions below in your notebook below this page.
1. Write two observations for slide 1.
2. Write two observations for slide 2.
3. Compare: List one way the two slides are the SAME.
4. Contrast: List one way the two slides are DIFFERENT.
5. Which slide do you think contains the most cells?
6. Why do you think it might negatively affect an individual to have fewer red blood cells in their body?
Crop and Glue into notebook.
Station 1: Red Blood Cell Viewing and Comparing
Directions: Below are images of red blood cells (erythrocytes = erythro-red/cytes-cells) on slides viewed
with a microscope. The picture on the left shows cells from a “normal” individual, whereas the picture on the
right shows cells from a person with sickle cell anemia.
Slides from
http://www.wadsworth.org/
chemheme/heme/microscope
Slide 1: Red blood cells from a
“normal” person
Slide 2: Red blood cells from a
person with sickle cell anemia
Analysis: Answer the questions below in your notebook below this page.
1. Write two observations for slide 1.
2. Write two observations for slide 2.
3. Compare: List one way the two slides are the SAME.
4. Contrast: List one way the two slides are DIFFERENT.
5. Which slide do you think contains the most cells?
6. Why do you think it might negatively affect an individual to have fewer red blood cells in their body?
Crop and glue into your notebook.
Station# 2: Model the Flow of Clay Blood Cells through Tube Capillaries
Directions: Use the materials on the lab tray to model how blood cells flow through very small blood
vessels called capillaries. The tube represents a capillary, and the red clay represents blood cells. Notice
that some of the clay is donut-shaped, and some is flattened into a crescent shape.
Complete the following two model scenarios and carefully observe the differences.
o Model 1: Hold the curved tube upright with the open end up and only allow round shaped cells to
flow through the tube.
o Model 2: Hold the curved tube upright with the open end up and allow a mixture of round and
crescent-shaped cells to flow through the tube.
Draw two boxes below this sheet in your notebook (about 2” X 2”). Label one Model 1 and
the other Model 2. Draw in a colored sketch of each model scenario in the correctly labeled
box. Use red colored pencils for the RBCs.
Analysis: Answer the questions below.
1. What does the tube represent in the body?
2. What do the red clay models represent in the body?
3. Compare how the flow of cells was the same in the two models.
4. Contrast how the flow of the cells was different between the models.
5. Explain how mis-shapen cells can change the flow of blood.
6. What symptoms do you think would result in a person who has crescent shaped blood cells and a
change in blood flow?
Crop and glue into your notebook.
Station# 2: Model the Flow of Clay Blood Cells through Tube Capillaries
Directions: Use the materials on the lab tray to model how blood cells flow through very small blood
vessels called capillaries. The tube represents a capillary, and the red clay represents blood cells. Notice
that some of the clay is donut-shaped, and some is flattened into a crescent shape.
Complete the following two model scenarios and carefully observe the differences.
o Model 1: Hold the curved tube upright with the open end up and only allow round shaped cells to
flow through the tube.
o Model 2: Hold the curved tube upright with the open end up and allow a mixture of round and
crescent-shaped cells to flow through the tube.
Draw two boxes below this sheet in your notebook (about 2” X 2”). Label one Model 1 and
the other Model 2. Draw in a colored sketch of each model scenario in the correctly labeled
box. Use red colored pencils for the RBCs.
Analysis: Answer the questions below.
1. What does the tube represent in the body?
2. What do the red clay models represent in the body?
3. Compare how the flow of cells was the same in the two models.
4. Contrast how the flow of the cells was different between the models.
5. Explain how mis-shapen cells can change the flow of blood.
6. What symptoms do you think would result in a person who has crescent shaped blood cells and a
change in blood flow?
Crop and Glue into your notebook.
Pedigree Construction and Analysis
Directions: Carefully read the description below about a family in which some members
have sickle cell anemia.
Joe and Jackie have four children and are expecting a baby. Two of their children (Angie and Bob) have sickle cell anemia, and their other two children (Carl and Debbie) do not have the disorder. Joe’s parents, Jackie’s Dad, and Jackie’s sister do not have the disorder. However, Joe’s brother has sickle cell anemia, and Jackie’s mom had the disorder and died as a young woman. Joe and Jackie ask you, a genetic counselor, how this disorder is inherited (dominant or recessive) and what the likelihood is that their unborn child will have sickle cell anemia. Below this paper in your notebook draw and label a pedigree for this family using the guidelines for
pedigree construction. You should include generation numbers, individual numbers, shaded
individuals for those that express the trait of sickle cell anemia and the genotypes of each individual
(use A and a). In this case, it would be useful to put names next to shapes in the pedigree for future
reference-write them small.
Analysis: Answer the following questions below your pedigree in outline format.
1. What is the pattern of inheritance of this disorder (dominant or recessive)?
2. Calculate the probability that Joe and Jackie’s unborn child will have sickle cell anemia. (You
may do a Punnett Square to determine the possibilities of allele combination outcomes.)
3. If Bob married and had a child with a woman who is homozygous for the normal allele, what
would be the probability of the child having sickle cell disease? What is the probability of the
child being heterozygous?
Crop and Glue into your notebook.
Pedigree Construction and Analysis
Directions: Carefully read the description below about a family in which some members
have sickle cell anemia.
Joe and Jackie have four children and are expecting a baby. Two of their children (Angie and Bob) have sickle cell anemia, and their other two children (Carl and Debbie) do not have the disorder. Joe’s parents, Jackie’s Dad, and Jackie’s sister do not have the disorder. However, Joe’s brother has sickle cell anemia, and Jackie’s mom had the disorder and died as a young woman. Joe and Jackie ask you, a genetic counselor, how this disorder is inherited (dominant or recessive) and what the likelihood is that their unborn child will have sickle cell anemia. Below this paper in your notebook draw and label a pedigree for this family using the guidelines for
pedigree construction. You should include generation numbers, individual numbers, shaded
individuals for those that express the trait of sickle cell anemia and the genotypes of each individual
(use A and a). In this case, it would be useful to put names next to shapes in the pedigree for future
reference-write them small.
Analysis: Answer the following questions below your pedigree in outline format.
1. What is the pattern of inheritance of this disorder (dominant or recessive)?
2. Calculate the probability that Joe and Jackie’s unborn child will have sickle cell anemia. (You
may do a Punnett Square to determine the possibilities of allele combination outcomes.)
3. If Bob married and had a child with a woman who is homozygous for the normal allele, what
would be the probability of the child having sickle cell disease? What is the probability of the
child being heterozygous?
7/13/2010
Red blood cell phenotypes and blood flow in normal
people and people with sickle cell anemia
Sickle Cell Anemia:
Genotype to Phenotype
Heidi Sleister & Denay Gray
GENA Lesson
April 2010
RBC smear from normal person
Sickle-shaped blood
cells can occlude
(block) capillaries.
This leads to anemia.
RBC smear from person with
sickle cell anemia
http://www.wadsworth.org/chemheme/heme/microscope
Hemoglobin Beta (HBB) gene
Are all mutations harmful?
Gene Location:
Human chromosome 11p15.5
• Types of substitution mutations
– Missense mutation
– Silent mutation
– Nonsense mutation
*Chromosome 11 is an autosome
Gene Size: 1600 base pairs
Messenger RNA Size: 626 nucleotides
Coding Sequence Size: 444 base pairs
Polypeptide Size: 146 amino acids
http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/hbb.shtml
Hb A ALLELE (normal allele)
RNA-like
Template
5’- ATG GTG CAT CTG ACT CCT GAG GAG AAG TCT…-3’
3’- TAC CAC GTA GAC TGA GGA CTC CTC TTC AGA…-5’
mRNA
5’- AUG GUG CAU CUG ACU CCU GAG GAG AAG UCU…-3’
Hb A ALLELE (normal allele)
RNA-like
Template
5’- ATG GTG CAT CTG ACT CCT GAG GAG AAG TCT…-3’
3’- TAC CAC GTA GAC TGA GGA CTC CTC TTC AGA…-5’
mRNA
5’- AUG GUG CAU CUG ACU CCU GAG GAG AAG UCU…-3’
TRANSCRIPTION
TRANSCRIPTION
TRANSLATION
TRANSLATION
Protein
N-…Met Val His Leu Thr Pro Glu Glu Lys Ser…-C
RNA-like
Template
5’- ATG GTG CAT CTG ACT CCT GTG GAG AAG TCT…-3’
3’- TAC CAC GTA GAC TGA GGA CAC CTC TTC AGA…-5’
mRNA
5’- AUG GUG CAU CUG ACU CCU GUG GAG AAG UCU…-3’
Protein
N-…Met Val His Leu Thr Pro Glu Glu Lys Ser…-C
RNA-like
Template
5’- ATG GTG CAT CTG ACT CCT GAA GAG AAG TCT…-3’
3’- TAC CAC GTA GAC TGA GGA CTT CTC TTC AGA…-5’
mRNA
5’- AUG GUG CAU CUG ACU CCU GAA GAG AAG UCU…-3’
Hb S ALLELE (mutant allele)
New mutant allele…
TRANSCRIPTION
TRANSCRIPTION
TRANSLATION
Protein
TRANSLATION
N-…Met Val His Leu Thr Pro ? Glu Lys Ser…-C
Val
(Missense mutation)
Protein
N-…Met Val His Leu Thr Pro
?
Glu
Glu Lys Ser…-C
(Silent mutation)
1
7/13/2010
Hb A ALLELE (normal allele)
RNA-like
Template
5’- ATG GTG CAT CTG ACT CCT GAG GAG AAG TCT…-3’
3’- TAC CAC GTA GAC TGA GGA CTC CTC TTC AGA…-5’
mRNA
5’- AUG GUG CAU CUG ACU CCU GAG GAG AAG UCU…-3’
What is Hemoglobin?
TRANSCRIPTION
TRANSLATION
• Hemoglobin is a protein found in red blood cells
Protein
N-…Met Val His Leu Thr Pro Glu Glu Lys Ser…-C
• Hemoglobin is made up of 4 polypeptide subunits
(2 alpha, 2 beta)- tetramer
Another new mutant allele…
RNA-like
Template
5’- ATG GTG CAT CTG ACT CCT TAG GAG AAG TCT…-3’
3’- TAC CAC GTA GAC TGA GGA ATC CTC TTC AGA…-5’
– HBB codes for hemoglobin beta, HBA codes for hemoglobin alpha
• Hemoglobin carries oxygen which is needed in body tissues
TRANSCRIPTION
mRNA
5’- AUG GUG CAU CUG ACU CCU UAG GAG AAG UCU…-3’
TRANSLATION
Protein
N-…Met Val His Leu Thr Pro
-
?
Glu Lys Ser…-C
(Nonsense mutation)
What happens when the HBB gene is mutated?
• People with sickle cell anemia have two defective HbS alleles
(instead of normal HbA alleles).
Is the structure of hemoglobin tetramers in normal
people and people with sickle cell anemia different?
Hb tetramer in normal people
Hb tetramer in people with
sickle cell anemia
– The HbS allele has a substitution of a single base pair in codon 6
– This mutation results in a glutamic acid to valine change at amino acid 6
– Valine is a hydrophobic amino acid
• Expression of the HbS allele results in a hemoglobin tetramer
with mutant beta hemoglobin subunits. (view picture)
• The problem is that the hemoglobin tetramers made from HbS
alleles are “sticky” and aggregate (clump) to form long fibers.
• These long fibers cause the red blood cell to have a sickle
shape.
Hemoglobin tetramers in people with the
HbS/HbS genotype stick together!
http://www.rcsb.org/pdb/cgi/explore.cgi?pid=1679106339
4243&page=0&pdbId=4HHB
http://www.rcsb.org/pdb/cgi/explore.cgi?pid=18121063394
293&page=0&pdbId=2HBS
How does the
HbS/HbS
genotype in
people with
sickle cell
anemia cause
sickle-shaped
red blood
cells?
http://www.rcsb.org/pdb/explore/images.do?structureId=2HBS
Hartwell et al. 2008. Genetics: Genes to Genomes, McGraw-Hill
2
7/13/2010
Genotype
(HbA/HbA or HbA/HbS)
Genotype
Phenotype
Phenotype
Hemoglobin
protein
Red blood cell
Person
Hemoglobin
protein
Red blood cell
Person
Normal
tetramers
Normal in
shape (donut)
and number
Normal
Is sickle cell anemia found more often in
certain ethnic groups?
Genotype
(HbS/HbS)
Phenotype
Hemoglobin
protein
Red blood cell
(RBC)
Person
Tetramers stick
together and
form long fibers
Abnormal
shape (sickle),
fewer RBCs
Sickle cell anemia
Am J Epidemiol Vol. 151, No. 9, 2000
How is sickle cell anemia treated?
The End
• Blood transfusions
– Build-up of iron is a problem
• Hydroxyurea medication (causes switch to
expression of fetal hemoglobin)
– Can be toxic
3
7/13/2010
Hemoglobin beta mRNA
1
61
121
181
241
301
361
421
481
541
601
acauuugcuu
ugacuccuga
uuggugguga
aguccuuugg
auggcaagaa
gcaccuuugc
ucaggcuccu
ccccaccagu
acaaguauca
cuaaguccaa
uaauaaaaaa
cugacacaac
ggagaagucu
ggcccugggc
ggaucugucc
agugcucggu
cacacugagu
gggcaacgug
gcaggcugcc
cuaagcucgc
cuacuaaacu
cauuuauuuu
uguguucacu
gccguuacug
aggcugcugg
acuccugaug
gccuuuagug
gagcugcacu
cuggucugug
uaucagaaag
uuucuugcug
gggggauauu
cauugc
agcaaccuca
cccugugggg
uggucuaccc
cuguuauggg
auggccuggc
gugacaagcu
ugcuggccca
ugguggcugg
uccaauuucu
augaagggcc
aacagacacc
caaggugaac
uuggacccag
caacccuaag
ucaccuggac
gcacguggau
ucacuuuggc
uguggcuaau
auuaaagguu
uugagcaucu
auggugcauc
guggaugaag
agguucuuug
gugaaggcuc
aaccucaagg
ccugagaacu
aaagaauuca
gcccuggccc
ccuuuguucc
ggauucugcc
Hemoglobin beta protein
Met-Val-His-Leu-Thr-Pro-Glu-Glu-Lys-Ser-Ala-Val-Thr-Ala-Leu-Trp-GlyLys-Val-Asn-Val-Asp-Glu-Val-Gly-Gly-Glu-Ala-Leu-Gly-Arg-Leu-Leu-ValVal-Tyr-Pro-Trp-Thr-Gln-Arg-Phe-Phe-Glu-Ser-Phe-Gly-Asp-Leu-Ser-ThrPro-Asp-Ala-Val-Met-Gly-Asn-Pro-Lys-Val-Lys-Ala-His-Gly-Lys-Lys-ValLeu-Gly-Ala-Phe-Ser-Asp-Gly-Leu-Ala-His-Leu-Asp-Asn-Leu-Lys-Gly-ThrPhe-Ala-Thr-Leu-Ser-Glu-Leu-His-Cys-Asp-Lys-Leu-His-Val-Asp-Pro-GluAsn-Phe-Arg-Leu-Leu-Gly-Asn-Val-Leu-Val-Cys-Val-Leu-Ala-His-His-PheGly-Lys-Glu-Phe-Thr-Pro-Pro-Val-Gln-Ala-Ala-Tyr-Gln-Lys-Val-Val-AlaGly-Val-Ala-Asn-Ala-Leu-Ala-His-Lys-Tyr-His
4
Sickle Cell Anemia POWERPOINT QUESTIONS Directions: Answer these questions in the spaces provided from the PowerPoint presentation in class. 1. Why is hemoglobin important for our bodies? _______________________________________________________________ 2. What is the name of the gene that, when mutant, causes sickle cell anemia? _______________________________________________________________ 3. Where is the human HBB gene located? _____________________ 4. Where is the specific mutation in the HbS allele at the DNA level? ____________________ What is this type of mutation called? ________________________ 5. How is the beta‐hemoglobin polypeptide expressed from the HbS allele different from the beta‐
hemoglobin polypeptide expressed from the HbA allele? ______________________________________________________________________________ 6. Describe the structure of hemoglobin protein in “normal” individuals. ______________________________________________________________________________ 7. Describe the structure of the hemoglobin protein in people with sickle cell anemia. ______________________________________________________________________________ 8. How does the structure of the hemoglobin protein affect the shape of red blood cells in people with sickle cell anemia? __________________________________________________________ 9. What problems exist for people with sickle‐shaped red blood cells? ______________________________________________________________________________ 10. Why is it a problem for people to have a decreased number of red blood cells? ______________________________________________________________________________ Sickle Cell Anemia POWERPOINT QUESTIONS Directions: Answer these questions in the spaces provided from the PowerPoint presentation in class. 1. Why is hemoglobin important for our bodies? _______________________________________________________________ 2. What is the name of the gene that, when mutant, causes sickle cell anemia? _______________________________________________________________ 3. Where is the human HBB gene located? _____________________ 4. Where is the specific mutation in the HbS allele at the DNA level? ____________________ What is this type of mutation called? ________________________ 5. How is the beta‐hemoglobin polypeptide expressed from the HbS allele different from the beta‐
hemoglobin polypeptide expressed from the HbA allele? ______________________________________________________________________________ 6. Describe the structure of hemoglobin protein in “normal” individuals. ______________________________________________________________________________ 7. Describe the structure of the hemoglobin protein in people with sickle cell anemia. ______________________________________________________________________________ 8. How does the structure of the hemoglobin protein affect the shape of red blood cells in people with sickle cell anemia? __________________________________________________________ 9. What problems exist for people with sickle‐shaped red blood cells? ______________________________________________________________________________ 10. Why is it a problem for people to have a decreased number of red blood cells? ______________________________________________________________________________ Sequence analysis of hemoglobin beta alleles
Below is a portion of the DNA base pair sequence for the human hemoglobin beta (HBB) gene. Both strands of the DNA double helix are listed ‐ these are called the template strand and the RNA‐like strand. In transcription, RNA polymerase synthesizes (builds) a single strand of messenger RNA (mRNA) complementary and antiparallel to the gene’s template strand. In translation, codons in the mRNA are read by the ribosome to produce a polypeptide chain of amino acids. Directions: The top DNA sequence represents the normal HbA (wild-type) allele for the HBB gene
and the bottom DNA sequence represents the abnormal “sickle” allele HbS. First, look for and circle
the difference in the DNA sequences of the HbA and HbS alleles. THEN, write the mRNA and amino
acid sequences that would result from transcription and translation of each of the alleles below. Use the
codon wheel in your notebook—abbreviate the amino acids to the first three letters.
Wild-type (normal) allele HbA
RNA-like strand 5’-ATG GTG CAT CTG ACT CCT GAG GAG AAG TCT…-3’
Template strand 3’-TAC CAC GTA GAC TGA GGA CTC CTC TTC AGA…-5’
TRANSCRIPTION
mRNA sequence 5’-_______________________________________…-3’
TRANSLATION
Polypeptide
N -___ ___ ___ ___ ___ ___ ___ ___ ___ ___…-C
Mutant (sickle) allele HbS
RNA-like strand 5’-ATG GTG CAT CTG ACT CCT GTG GAG AAG TCT…-3’
Template strand 3’-TAC CAC GTA GAC TGA GGA CAC CTC TTC AGA…-5’
TRANSCRIPTION
mRNA sequence 5’-_______________________________________…-3’
TRANSLATION
Polypeptide
N -___ ___ ___ ___ ___ ___ ___ ___ ___ ___…-C
Analysis: Answer the questions below.
1. Describe the change found in the DNA sequence of the sickle allele (be as specific as you can).
________________________________________________________________________
2. In this change, how many nucleotides are affected? ___________
3. How many corresponding codons and amino acids are affected? Codons _____ Amino Acids_____
4. How does this change effect the protein that is produced by this gene?
________________________________________________________________________
Sequence analysis of hemoglobin beta (HBB) alleles: Follow-up
Directions: Now that you have determined the mRNA and amino acid sequences that would
result from transcription and translation of the HbA and HbS alleles, use this same strategy for
a new mutant allele called Allele HbX. Circle the difference in the DNA sequence between the
HbA and HbX allele. Write the mRNA and amino acid sequences that would result from
transcription and translation of allele HbX. The HbA allele has already been completed.
Wild-type (normal) allele HbA
RNA-like strand 5’-ATG GTG CAT CTG ACT CCT GAG GAG AAG TCT…-3’
Template strand 3’-TAC CAC GTA GAC TGA GGA CTC CTC TTC AGA…-5’
TRANSCRIPTION
mRNA sequence 5’-AUG GUG CAU CUG ACU CCU GAG GAG AAG UCU -3’
TRANSLATION
Polypeptide
N –Met Val His Leu Thr Pro Glu Glu Lys Ser -C
Mutant (sickle) allele HbX
RNA-like strand 5’-ATG GTG CAT CTG ACT CCT GAG GAA AAG TCT…-3’
Template strand 3’-TAC CAC GTA GAC TGA GGA CTC CTA TTC AGA…-5’
TRANSCRIPTION
mRNA sequence 5’-_______________________________________…-3’
TRANSLATION
Polypeptide
N -___ ___ ___ ___ ___ ___ ___ ___ ___ ___…-C
Analysis: Answer the questions below.
1. Specifically describe the change found in the DNA sequence of Allele HbX.
____________________________________________________________
2. How many nucleotides are affected? _________________
3. How many corresponding amino acids are affected? _______________
4. How do you think this mutation would affect an individual who has two copies of Allele
HbX? Would this mutation be harmful?
____________________________________________________________
Name:______________________________ Block: ___________ Date: _______________ Biology: Genetics – POSTTEST Directions: Complete each of the following questions to the best of your ability. 1. Which is SMALLER: a gene or a chromosome? ________________ Explain your answer: 2.
Write two pieces of information that you can learn about a person’s genetics by studying their pedigree. a. ________________________________________ b. ________________________________________ Questions #3‐7 refer to the pedigree below. 3.
4.
5.
6.
7.
Is the trait represented in this pedigree dominant or recessive? ________________ How do you know? ________________________________________________________________________ Is person III‐2 affected? _________ Is person II‐2 heterozygous? ________ What is the genotype of the person at I‐1? _________ What is the genotype of the person at II‐5? _________ 8. Which of the following molecules provides the master code for the functions carried out by the cell? a. DNA b. mRNA c. tRNA d. amino acids 9.
Using the template DNA sequence 3’ TTGATAGCACCC 5’, answer the following questions: a. What would be the corresponding mRNA sequence: ______________________ b. How many codons would be in the corresponding mRNA sequence? ______ c. How many amino acids would be determined by this sequence? ______ 10. Using the chart on separate paper, determine the amino acids that would be coded for by the DNA sequence found in Question #9 above. (write out full names of amino acids) __________________________________________________________________________________ 11.
Put an X next to each statement that you think is TRUE. Mark all that apply. a. DNA molecules are sometimes replicated with changes or mutations in the nucleotide sequence. b. If there is a change in a DNA base sequence, only the DNA molecule is affected. c. A person’s phenotype is not affected by their genotype. d. The DNA sequence for a gene would have to have several changes for its resulting product to function improperly. e. The outcome is always negative (harmful) on an organism when DNA bases are changed. f. A phenotype is what you see when a person’s genes are all NORMAL. g. It is possible for a gene to have a nucleotide sequence change and still function properly. h. Some genetic diseases can occur only in one or a few ethnic groups. For example, sickle cell anemia only affects African Americans. i. A person who has sickle cell anemia has the sickle cell gene. j. A person has two copies of each gene located on an autosome. 12. What type of organic molecule is hemoglobin? _________________________ 13. Why is hemoglobin important for our bodies? _______________________________________________________________ 14. What type of mutation causes the beta hemoglobin gene to be defective? a. Silent mutation b. Missense mutation c. Nonsense mutation 15. How many alleles does a person need to have a phenotype that expresses the sickle cell anemia disorder? ____________ Please explain your answer clearly. ___________________________________________________________________________________
_________________________________________________________________________________ 16. Describe the structure of the hemoglobin tetramer (4 part) protein in “normal” individuals. ______________________________________________________________________________ 17. Describe the structure of the hemoglobin tetramer (4 part) protein in people with sickle cell anemia. ______________________________________________________________________________ 18. What is it about the defective hemoglobin proteins that cause it to behave abnormally (at the amino acid level)? ________________________________________________________________________ 19. From where does this defect originate (which molecule)? __________________ 20. How does the structure of the hemoglobin protein affect the shape of red blood cells in people with sickle cell anemia? __________________________________________________________ 21. What problems/symptoms exist for people with sickle‐shaped red blood cells? ______________________________________________________________________________ 22. Why is it a problem for people to have a decreased number of red blood cells? ______________________________________________________________________________ 23. How do you think a cell would behave differently if a part of the DNA sequence was changed? What molecules would be affected and how would the organism, as a whole, be different, if at all? OPENER – Sickle Cell Anemia Lessons Reflection:
Over the past three blocks we have been working our way through a set of lessons designed in
collaboration with Dr. Sleister, a Drake University genetics professor. Over the course of those three
blocks, we reviewed different concepts learned over the course of the semester (as far back as January)
and applied them to a “big picture concept” of correlating genotype with phenotype using sickle cell
anemia as a focal point. Please take a few minutes and review the materials we used over these few
days from your notebook. We, as your teachers, would very much like your feedback on those lessons so
we can make adjustments for the future. To that end, please answer the following questions honestly,
completely and respectfully. You may put your name on this paper if you would like, but it is not
required. Thank you in advance for your input!!
a. What things did you like best about the lessons on the genotype and phenotype of sickle cell anemia? Please explain. b. What parts did you like least about these lessons? Please explain. c. Write one or two things about sickle cell anemia, genotype, phenotype, etc, that you NOW clearly understand having worked through these lessons in class. d. Write any questions you still have. e. What advice do you have for us from a student’s perspective to make these lessons better? OPENER – Sickle Cell Anemia Lessons Reflection:
Over the past three blocks we have been working our way through a set of lessons designed in
collaboration with Dr. Sleister, a Drake University genetics professor. Over the course of those three
blocks, we reviewed different concepts learned over the course of the semester (as far back as January)
and applied them to a “big picture concept” of correlating genotype with phenotype using sickle cell
anemia as a focal point. Please take a few minutes and review the materials we used over these few
days from your notebook. We, as your teachers, would very much like your feedback on those lessons so
we can make adjustments for the future. To that end, please answer the following questions honestly,
completely and respectfully. You may put your name on this paper if you would like, but it is not
required. Thank you in advance for your input!!
a. What things did you like best about the lessons on the genotype and phenotype of sickle cell anemia? Please explain. b. What parts did you like least about these lessons? Please explain. c. Write one or two things about sickle cell anemia, genotype, phenotype, etc, that you NOW clearly understand having worked through these lessons in class. d. Write any questions you still have. e. What advice do you have for us from a student’s perspective to make these lessons better?