Download CentralDogmaKeys for Disease Wkstsv2

Name:_____Cystic Fibrosis Key_________________________________________
Imagine that you are an ER physician. One day, a father arrives with his newborn son, Jacob, who has had a
cough for days and sounds like he is wheezing. During your examination, you discover that he also has salt
crystals forming on his skin. You suspect that Jacob may have cystic fibrosis. In order to determine this, you
order a genetic test to compare Jacob’s DNA to the known sequence of normal (non-disease) DNA. Specifically,
the genetic test is used to look for abnormalities in a portion of the CFTR gene, a gene that is associated with
cystic fibrosis. Examine the results (below) from the DNA test to determine if there are any nucleotide changes in
Jacob’s CFTR gene.
1. First look at the control nucleotide sequence from an individual that has a normal CFTR gene. Note
that this is a sequence from the middle of the CFTR gene.
DNA sequence for the non-template strand:
5’- A T C A T C T T T G G T G T T-3’
Write out the DNA sequence for the template strand. Label the 5’ and 3’ ends.
3’-T A G T A G A A A C C A C A A -5’
Write out the mRNA sequence. Label the 5’ and 3’ ends.
5’- A U C A U C U U U G G U G U U-3’
Write out the amino acid sequence using the codon table, and label the N and C termini. (HINT: use the
first 3 nucleotides of the mRNA for the first codon—there is no start codon because this sequence in is
from the middle of the gene.)
N- Ile-Ile-Phe-Gly-Val -C
2. Now examine the sequence of the non-template strand of Jacob’s CFTR gene:
5’- A T C A T C G G T G T T -3’
Write out the DNA sequence for the template strand. Label the 5’ and 3’ ends.
3’- T A G T A G C C A C A A -5’
Write out the mRNA sequence. Label the 5’ and 3’ ends.
5’- AUC AUC GGU GUU-3’
Write out the amino acid sequence using the codon table, and label the N and C termini. (HINT: use the
first 3 nucleotides of the mRNA for the first codon—there is no start codon because this sequence in is
from the middle of the gene.)
N- Ile-Ile-Gly-Val -C
Compare the amino acid sequence from the non-diseased individual to Jacob’s sequence to determine if
there are any differences. If you do detect a difference, please describe the result in complete sentences:
A deletion in the nucleotide sequence leads to a polypeptide sequence that is missing Phe
3. As you have discovered, the results of the genetic test show that a mutation in Jacob’s CFTR gene
alters the amino acid sequence of the CFTR protein. Using the information in your packet, write a brief
explanation of how these amino acid changes affect the CFTR protein structure.
When Phe is deleted from the CFTR protein, the protein does not fold correctly. Normally when
the CFTR protein is synthesized, it is transported to the ER and the Golgi, before being inserted in
the plasma membrane. When the CFTR protein is misfolded, the ER recognizes that there is a
problem with the protein structure and the protein is targeted for degradation. As a consequence
the misfolded CFTR protein does not reach the plasma membrane.
4. Next, describe some of the common symptoms found in patients with cystic fibrosis. How do the
structural changes in the CFTR protein lead to these symptoms?
Patients that have cystic fibrosis have excess amounts of salt in their sweat and accumulation of
mucus in various organs. CF patients show these symptoms because the CFTR protein, which
plays an important role in transporting chloride ions across the membrane, is no longer present in
the plasma membrane of cells. The loss of Cl- ion transport disrupts the sodium and chloride
balanced needed to maintain a thin mucus layer around organs such as the lungs. In CFTR
patients, a thick mucus layer surrounds organs, which can trap bacteria and lead to chronic
infections.
5. Jacob’s father is worried that his other child named Sarah may also have cystic fibrosis so he insists
that she have the test as well. Her DNA sequence for the non-template strand of the CFTR gene is:
5’- A T C A T C T T C G G T G T T-3’
Does Sarah also have a mutation that affects the CFTR protein structure? Explain your answer (please
show the sequence for the template strand, mRNA, and polypeptide, and label the 5’ and 3’ ends and the
N and C termini).
Template strand: 3’-TAG TAG AAG CCA CAA-5’
mRNA: 5’-AUC AUC UUC GGU GUU-3’
Polypeptide: N- Ile-Ile-Phe-Gly-Val -C
Sarah’s mutation does not affect the CFTR protein structure because the mutation is silent
Name:_______Hereditary Hemochromatosis Key___________________________
Imagine that you are a family practice physician. One day, an older woman named Chris comes
into your office. Chris is post-menopausal, is suffering from joint pain, and says that she now feels
tired all the time. Because it is a common disorder, you suspect that Chris may have hereditary
hemochromatosis. In order to determine this, you order a genetic test to compare Chris’ DNA to
the known sequence of normal (non-disease) DNA. Specifically, the genetic test is used to look for
abnormalities in a portion of the hemochromatosis gene, a gene that is associated with hereditary
hemochromatosis. Examine the results (below) from the DNA test to determine if there are any
changes in Chris’ hemochromatosis gene.
1. First look at the control nucleotide sequence from an individual that has a normal hemochromatosis
gene. Note that this is a sequence from the middle of the gene.
DNA sequence for the non-template strand:
5’- A G A T A T A C G T G C C A G G T G G A G-3’
Write out the DNA sequence for the template strand. Label the 5’ and 3’ ends.
3’-TCT ATA TGC ACG GTC CAC CTC-5’
Write out the mRNA sequence. Label the 5’ and 3’ ends.
5’- AGA UAU ACG UGC CAG GUG GAG-3’
Write out the amino acid sequence using the codon table, and label the N and C termini. (HINT: use the
first 3 nucleotides of the mRNA for the first codon—there is no start codon because this sequence in is
from the middle of the gene.)
N-Arg-Tyr-Thr-Cys-Gln-Val-Glu-C
2. Now examine the sequence of the non-template strand of Chris’ hemochromatosis gene. Note that
this is a sequence from the middle of the gene.
DNA sequence for the non-template strand:
5’- A G A T A T A C G T A C C A G G T G G A G-3’
Write out the DNA sequence for the template strand. Label the 5’ and 3’ ends.
3’-TCT ATA TGC ATG GTC CAC CTC-5’
Write out the mRNA sequence. Label the 5’ and 3’ ends.
5’- AGA UAU ACG UAC CAG GUG GAG-3’
Write out the amino acid sequence using the codon table, and label the N and C termini:
(use the first 3 nucleotides of the mRNA for the first codon—there is no start codon because this
sequence in is from the middle of the gene).
N- Arg-Tyr-Thr-Tyr-Gln-Val-Glu- C
Compare the amino acid sequence from the non-diseased individual to Chris’ sequence to determine if
there are any differences. If you do detect a difference, please describe the result in complete sentences:
A single base pair change in the nucleotide sequence leads to a polypeptide sequence in which Tyr
replaces Cys
3. As you have discovered, the results of the genetic test showed that a mutation in Chris’
hemochromatosis gene alters the amino acid sequence of the hemochromatosis protein. Using the
information in your packet, write a brief explanation of how these amino acid changes affect the
hemochromatosis protein structure.
When tyrosine is substituted for cysteine, a disulfide bond that normally forms a loop in a domain
of the hemochromatosis protein is disrupted. Consequently, this domain is not properly formed
and the hemochromatosis protein can no longer complex with a stabilization factor known as beta2-microglobulin. Without the stabilization factor, the hemochromatosis protein is degraded
before it reaches the cell membrane.
4. Next, describe some of the common symptoms found in patients with hereditary hemochromatosis.
How do the structural changes in the hemochromatosis protein lead to these symptoms?
Patients with hereditary hemochromatosis have joint problems and may have fatigue, a lack of
energy, abdominal pain, loss of sex drive, and heart problems. Normally the hemochromatosis
protein is incorporated into the plasma membrane where its job is to regulate iron flow into the
cell’s cytoplasm. However, when the hemochromatosis protein is improperly folded, it is not
incorporated in the plasma membrane and can no longer limit the about of iron getting into the
cell. Iron overload in cells can damage tissues and organs.
5. Chris is worried that her younger sister named Eve may also have hereditary hemochromatosis, so
she insists that her sister have the test as well. Eve’s DNA sequence for the non-template strand of the
hemochromatosis gene is:
5’- A G A T A T A C G T G T C A G G T G G A G-3’
Does Eve also have a mutation that affects the hemochromatosis protein structure? Explain your answer
(please show the sequence for the template strand, mRNA, and polypeptide, and label the 5’ and 3’ ends
and the N and C termini).
Template strand: 3’-TCT ATA TGC ACA GTC CAC CTC-5’
mRNA:
5’- AGA UAU ACG UGU CAG GUG GAG-3’
Polypeptide: N- Arg-Tyr-Thr-Cys-Gln-Val-Glu -C
Eve’s mutation does not affect the hemochromatosis protein structure because the mutation is
silent
Name:_______ Sickle Cell Anemia Key___________________________
Imagine that you are a hematologist and one day a boy named Jason comes into your office. Jason is having
episodes of intense pain and initial laboratory tests show that he is anemic. You suspect that Jason may have
sickle cell anemia. In order to determine this, you order a genetic test to compare Jason’s DNA to the known
sequence of normal (non-disease) DNA. Specifically, the genetic test is used to look for abnormalities in a
portion of the hemoglobin gene, a gene that when mutant may lead to sickle cell anemia. Examine the results
(below) from the DNA test to determine if there are any nucleotide changes in Jason’s hemoglobin .
1. First look at the control nucleotide sequence from an individual that has a normal hemoglobin gene.
Note that this is a sequence from the middle of the hemoglobin gene.
DNA sequence for the non-template strand:
5’- C T G A C T C C T G A G G A G A A G T C T-3’
Write out the DNA sequence for the template strand. Label the 5’ and 3’ ends.
3’-GAC TGA GGA CTC CTC TTC AGA-5’
Write out the mRNA sequence. Label the 5’ and 3’ ends.
5’- CUG ACU CCU GAG GAG AAG UCU-3’
Write out the amino acid sequence using the codon table, and label the N and C termini. (HINT: use the
first 3 nucleotides of the mRNA for the first codon—there is no start codon because this sequence in is
from the middle of the gene.)
N- Leu Thr Pro Glu Glu Lys Ser- C
2. Now examine the sequence for the non-template strand of Jason’s hemoglobin gene:
5’- C T G A C T C C T G T G G A G A A G T C T-3’
Write out the DNA sequence for the template strand. Label the 5’ and 3’ ends.
3’-GAC TGA GGA CAC CTC TTC AGA-5’
Write out the mRNA sequence. Label the 5’ and 3’ ends.
5’- CUG ACU CCU GUG GAG AAG UCU-3’
Write out the amino acid sequence using the codon table, and label the N and C termini. (HINT: use the
first 3 nucleotides of the mRNA for the first codon—there is no start codon because this sequence in is
from the middle of the gene.)
N- Leu Thr Pro Val Glu Lys Ser -C
Compare the amino acid sequence from the non-diseased individual to Jason’s sequence to determine if
there are any differences. If you do detect a difference, please describe the result in complete sentences:
A single base pair change in the nucleotide sequence leads to a polypeptide sequence in which Val
replaces Glu
3. As you have discovered, the results of the genetic test show that a mutation in Jason’s hemoglobin
gene alters the amino acid sequence. Using the information in your packet, write a brief explanation of
how these amino acid changes affect the hemoglobin protein structure.
When valine is substituted for glutamic acid, a hydrophobic amino acid takes the place of a
hydrophilic one. This change leads to a hydrophobic spot on the outside of the hemoglobin
protein. These hydrophobic spots stick to hydrophobic spots on other hemoglobin molecules,
resulting in the clumping together of hemoglobin molecules into rigid structures. These rigid
structures cause the sickling of red blood cells.
4. Next, describe some of the common symptoms found in patients with sickle cell anemia. How do the
structural changes in the hemoglobin protein lead to these symptoms?
Sickle cell anemia patients have chronic anemia and periodic episodes of pain. These symptoms
are caused by red blood cells with rigid cell membranes. The rigid cell membranes form because
the hemoglobin protein in sickle cell anemia patients fluctuates between polymerized and
depolymerized states. More specifically, after red blood cells release oxygen to tissues, hemoglobin
proteins in sickle cell anemia patients clump together (polymerization). When the cells return to
the lungs to bind oxygen, the long polymers of hemoglobin break apart (depolymerization).
Overtime, the cycling between the polymerized and depolymerized hemoglobin protein causes red
blood cell membrane rigidity. In sickle cell anemia patients, rigid red blood cells in combination
with the distorted sickle shape when they are not carrying oxygen, results in blockage of small
blood vessels. This blockage can cause pain and damage organs.
5. Because sickle cell anemia is a genetic disorder, you are worried that Jason’s baby sister Amy may
also have the disease. You decide to do a genetic test on her also. Her DNA sequence for the nontemplate strand of the hemoglobin gene is:
5’- C T G A C T C C T G A A G A G A A G T C T-3’
Does Amy also have a mutation that affects the hemoglobin protein structure? Explain your answer
(please show the sequence for the template strand, mRNA, and polypeptide, and label the 5’ and 3’ ends
and the N and C termini).
Template strand: 3’-GAC TGA GGA CTT CTC TTC AGA-5’
mRNA: 5’- CUG ACU CCU GAA GAG AAG UCU-3’
Polypeptide: N- Leu Thr Pro Glu Glu Lys Ser -C
The mutation in Amy’s nucleotide sequence does not affect the hemoglobin protein structure
because the mutation is silent