“Fixing” Gene Expression

Card Activity
Student Handout
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INTRODUCTION
Hemophilia is a rare genetic disorder in which the blood does not clot properly because it lacks sufficient blood-
clotting proteins. The disease is caused by mutations in a gene on the X chromosome. Because males typically
have only one X chromosome, to inherit the disease, they only need to inherit one copy of the mutated gene,
whereas females with two copies of the X chromosome must inherit two copies of the mutated gene. Symptoms
of the disease vary but generally include excessive internal and external bleeding. Currently, there is no long-
term cure, and many patients receive infusions of blood-clotting proteins. Because the disease is caused by
mutations in the DNA, scientists think that they could someday treat it by intervening in the steps that occur
from DNA to protein production. This flow of information represents the way most genes are expressed in
eukaryotic cells and is also referred to as the central dogma of molecular biology. How would knowledge of the
central dogma help find a treatment for hemophilia?

You will place cards with drawings of cellular molecules in the order in which the steps occur in eukaryotic gene
expression, labeling all names and molecules as instructed. Then, answer the questions that your instructor
assigns.

QUESTIONS
1. A genotype is the complete genetic makeup of an individual, whereas a phenotype is all observable
characteristics of the individual. Because genes direct the production of proteins and proteins are
responsible for an individual’s observable characteristics, genotypes control phenotypes.

The final card in the series shows a mature

protein. Proteins can play several different
cellular functions, as shown in the figure below.
Using prior knowledge, describe a specific role
each type of protein performs for the cell and
provide an example of an actual protein (e.g.,
lactase). Write your answer for each picture in
the table below.
Structure Proteins MADE BY AMINO ACIDS
AND DETERMINE BY
THEM

Transport Proteins CAN FORM A

CHANNEL THAT IS
SPECIFIC FOR
CERTAIN
MOLECULES

Enzymes PROTEINS THAT HELP

SPEED UP THE

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 “Fixing” Gene Expression
Card Activity
Student Handout
METABOLISM

Channels UNIQUE
ARRANGEMENTS OF
AMINO ACIDS IN THE
EMBED IN THE CELL
MEMBRANE

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 Activity
Central Dogma Card Sorting Activity Student Handout

Questions 2-4 present different disease scenarios. For each one you are asked to
identify a way to treat the disease by targeting a specific molecule or step in the central dogma pathway.
Refer to your cards as you think of an answer and make sure you pick a different approach for each disease.

2. Cystic fibrosis is a devastating illness that affects the lungs, pancreas, and intestines. In 1989, researchers
discovered that the disease is caused by a mutation in a gene that produces a protein that channels chloride
across cellular membranes. People with two copies (or alleles) of the mutated gene have a buildup of mucus
in the lungs, intestines, and other organs due to non functioning or absent channel proteins. Suggest two
ways you could intervene to treat the disease by targeting the DNA molecule and justify why each approach
could be effective.
1. One way that we can treat Cystic fibrosis by targeting the DNA molecule is CRISPR-Cas9. This is a
technology that allows scientists to change a cell's DNA at a precise location. This will be effective
because scientists can use CRISPR-Cas9 to knock out a gene so that it is not expressed, or edit the
gene to correct a disease-causing mutation. This knocks out the mutated gene so that it is not
expressed.
2. Another way is to use Gene Therapy. Gene therapy is an experimental technology that allows
researchers to provide functioning copies of genes to cells with disease-causing versions of those
genes. This will be effective because the gene that causes Cystic Fibrosis will be replaced with the
therapeutic gene using the viral vector method.

3. Like cystic fibrosis, sickle cell anemia is an autosomal recessive condition. It can be caused by mutations in
the gene for β-globin (HBB). HBB is one of the two subunits of adult hemoglobin, the protein that carries
oxygen in red blood cells. People who inherit two copies of the mutation produce abnormal hemoglobin,
and their tissues are starved of oxygen. One interesting finding is that some individuals with HBB mutations
do not have sickle cell anemia because they have another mutation that allows them to produce fetal
hemoglobin throughout their lives. Fetal hemoglobin production is normally turned off after birth. Based on
this knowledge, suggest two ways you could treat sickle cell anemia by targeting the transcription step of
the fetal hemoglobin gene and justify why each approach might be effective.
1. One way to treat sickle cell anemia by targeting the transcription step is to use the Gene Switch
method. By using the Gene Switch method, they can alter certain cells that have a bad effect towards
the disease to turn off. On the other hand, we can also alter a gene that is beneficial and make it turn
on the whole time.
2. Exon Skipping: Another way to treat sickle cell anemia is to use Exon Skipping. Exon skipping is a
technology that changes how the primary RNA transcript of a gene with a disease-causing mutation is
spliced, removing the mutation from the resulting mRNA. It will be effective because it will remove
the mutation completely.

4. Another disease caused by a mutation in a single gene is Huntington’s disease (HD), an autosomal dominant
condition. It is caused by mutations in a gene required for normal nerve cell function. The mutations cause
abnormal proteins to be produced which “stick” together and accumulate in nerve cells, eventually
interfering with normal cell operations. Suggest two ways you could treat the disease by targeting the
translation step for the HD protein and justify why each approach might be effective.
1. RNA Interference: RNA interference (RNAi) technologies involve small RNA segments that target
various mRNAs for destruction, reducing the expression of certain genes. This is effective because we
can silence any gene we want.
2. We can also destroy the mRNA so that it cannot be translated.

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 Activity
Central Dogma Card Sorting Activity Student Handout

5. Consider hemophilia again. Identify two ways the researcher could design an
intervention to treat hemophilia, provide a brief explanation of each, and justify why each approach might
be effective.
Gene Therapy: Introducing a healthy gene into the proper blood cells that secrete the specific clotting factors

CRISPR-Cas9: CRISPR-Cas9 to edit the gene in the proper blood cells that secrete the specific clotting factors

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