PBS unit 3
Why is sickle cell anemia classified as a recessive disorder?
its caused by a recessive gene. That means that both parents need to be a carrier, which they have the gene but don't show it, or the parents have the disease and pass it on
Can a genetic disease such as sickle cell anemia be diagnosed with a karyotype? Why or why not?
no because sickle cell disease is a point mutation with DNA, and a karyotype wouldn't be able to detect that specific mutation
Why does the sickling of red blood cells cause health problems?
oxygen isn't supplied to the body because of the blockages of blood vessels so it causes health issues like pain, fatigue, and delayed growth
can changing just one nucleotide in a gene change the shape of a protein
yes, the changing nucleotide will change the codon and therefore change the amino acid in the chain which changes the protein made
What does the map of the prevalence of hemoglobin disorders worldwide indicate about the disease?
it's most common in Africa
what determines the shape of a protein
the sequence and structure of amino acids
Explain how a genetics counselor or a doctor could use these calculations of probability to counsel prospective parents.
they could figure out the genotypes of the parents to do punnett squares to find out where the disease will be present in their children
How are traits passed through the generations?
when organisms reproduce , traits are passed from parent to offspring through DNA
how is dna passed to new cells during cell division
with the use of chromosomes
Explain why being able to view chromosomes from an individual is a useful tool for scientists and medical professionals.
how the chromosome is shaped will determine if something is wrong. For example, the 21st chromosome has 3 instead of 2 chromatids and we know that because of the karytope
What type of mutation is the sickle hemoglobin mutation?
A point mutation (substitution) because thymine is substituted for adenine and only one amino acid is changed.
what are some symptoms of sickle cell disease
-Anemia and Fatigue -Episodes of Pain -Frequent Infections and Fever -Vision Problems -Delayed Growth -Hand-foot syndrome/Dactylitis (swollen hands and feet) -Jaundice and Icteritus (yellow skin) -Acute chest syndrome -Dizziness, blue/gray fingernails, coldness in hands and feet, pale skin
what are the only "cures" for sickle cell disease
-Bone marrow transplant -Antibiotics -Folic acid tablets -hydroxyurea -red blood cell transfusion
What is the difference between normal and sickle hemoglobin at the DNA, RNA, and protein (amino acid) level?
-Healthy DNA: C A C G T G G A C T G A G G A C T C C T C -DNA with Sickle Mutation: C A C G T G G A C T G A G G A C A C C T C (point mutation where adenine replaces thymine) -Healthy RNA: G U G C A C C U G A C U C C U G A G G A G -RNA with Sickle Mutation: G U G C A C C U G A C U C C U G U G G A G -Healthy Protein: VAL HIS LEU THR PRO GLU GLU (sixth amino acid is changed from glutamic acid to valine) -Protein with Sickle Mutation: VAL HIS LEU THR PRO VAL GLU
People with sickle cell anemia often experience episodes of severe pain in their joints, chest, and abdomen and swelling in their hands and feet. Using what you know about the function of blood, why do you think the abnormal shape of sickled red blood cells causes these symptoms?
The misshapen cells can clog the blood vessels, keeping the oxygenated red blood cells from reaching those areas of the body.
Why do all the normal cells in the human body have the same number of chromosomes?
because we get 23 chromosomes from each parent
is the shape of a protein affected by its surrounded
yes, if the protein is under the effect of denaturing agents, its the shape will be changed and loses function
What do you think "allele frequency" means?
common allele that is prevalent in a population
Describe three ways daily life is affected for those who have sickle cell anemia.
1. Make and keep regular appointments with the SCD doctor or medical team 2. Deal with chronic pain 3. Deal with feelings of sadness or depression
What is the property of alanine (the amino acid that makes up this polymer chain) that helps explain its reaction to water and oil?
Alanine has no charge (is neutral), is non-polar and hydrophobic. So in water, alanine amino acids fold into a ball. They look as though they are trying to stick to each other. In oil, the alanine amino acids spread out.
Explain why the change in the way that molecules of b-globin interact with each other lead to the sickling of the red blood cells in sickle cell anemia
As more and more hemoglobin molecules begin to stick together, they start to form long fibers. These fibers push on the membrane of the red blood cell (remember that hemoglobins are the molecules that carry oxygen in red blood cells) and this causes the blood cell to change from the healthy disc shape to the crescent/sickled shape.
Why is it important that the end result of the process of meiosis is sex cells that contain half the amount of DNA that is in body cells?
Because the sex cells (egg and sperm) fuse in fertilization, they each need to have half the amount of DNA needed. This allows them together to provide the 46 chromosomes that make up the first body (somatic) cell at fertilization.
Based on what you know about blood, why would having a sickle cell anemia crisis result in a reduced red blood cell count, an elevated white blood cell count, and a reduced hematocrit?
Because the sickled red blood cells stick to arteries and veins they die quicker which lowers their numbers. White blood cells also start attacking the sickle cells because they are a different form which leads to a higher count of white blood cells and lower count of red blood cells. The elevated number of white blood cells could also be caused by physical stress from the sickle cell anemia which causes more white blood cells to be produced. Hematocrit is a measure of red blood cell values so lower numbers of red blood cells lead to reduced hematocrit.
Why do you think switching the hemoglobin gene's sixth amino acid from glutamic acid to valine would affect the hemoglobin protein?
Because valine is hydrophobic whereas glutamic acid is hydrophilic. With glutamic acid (healthy hemoglobin), the hemoglobin proteins do not sick together because they want as much surface area exposed to water as possible. With valine (the sickled hemoglobin), the hemoglobins sick together because they want to minimize the amount of surface area exposed to water. This causes fibers to form which push on the membranes of the red blood cells and cause them to take on a crescent or sickled shape.
how does the sequence of nucleotides in DNA determine the sequence of amino acids in a protein
DNA turns into mRNA and this determines the amino acid sequence
Was the mutational effect greater in a substitution or a deletion?
Deletion mutations (frameshift mutations, which also include insertion mutations) usually have a much greater effect on proteins as they change every amino acid from the point of the mutation to the end of the DNA/RNA strand.
Explain how DNA, chromosomes, and genes are related.
Genes make up DNA which makes up chromosomes
How are the properties of glutamic acid and valine different?
Glutamic acid is hydrophilic and negatively charged, whereas valine is hydrophobic and neutral
Explain how just a change of one amino acid has such an effect on SCD
Glutamic acid is hydrophilic so it spreads out to increase the amount of surface area exposed to water whereas the valine is hydrophobic so it folds inward to avoid contact with water. Since the polypeptide is a chain of amino acids, when valine folds inward, it brings the other amino acids inward with it.
What is the function of hemoglobin in the body?
Hemoglobin is a red protein found in the red blood cells of vertebrates that carries oxygen from the lungs to body tissues. Hemoglobin also carries carbon dioxide from body tissues back to the lungs.
Explain why more males are afflicted with hemophilia than females.
More males are afflicted with hemophilia than females because they only need to inherit one recessive allele for the disease (h), whereas females need to inherit two recessive alleles for the disease.
You fall down and scrape your hand - describe what each component of blood would be doing at the injury site.
PLATELETS clump to the sides of the torn blood vessels and make a plug to stop the bleeding. Clotting proteins build a protective layer to stop the bleeding and becomes a scab. WHITE BLOOD CELLS prevent infection after bleeding stops and destroy foreign objects. Fibroblasts produce collagen and fill in the wound and create new capillaries to bring RED BLOOD CELLS to recover the wound
Describe (in words) the effect of the mutation.
Point mutations (substitution) mutations only change one nucleotide. Therefore, only one amino acid is changed or may not change it at all. This can have little to no effect on the protein or it can change it greatly, as is the case with sickle cell disease.
How is the RNA molecule a "script" for the protein production process?
RNA is a "script" for the protein production process because the mRNA code determines which amino acids the tRNA brings to the ribosome for the rRNA to assemble into a protein.
Describe the difference between how sickle cell anemia is inherited versus how Best disease is inherited. What causes this difference?
Sickle cell anemia is an autosomal recessive disorder, which means that a child can only inherit the disease if both parents pass on a recessive allele for the disease (s). Best disease, however, is an autosomal dominant disease. This means that a child will inherit the disease if either parent passes on a dominant allele for the disease (B).
How does the abnormal shape of a sickled red blood cell affect its movement through blood vessels?
Sickle-shaped cells stick to the walls of small blood vessels and have difficulty passing through them.
Explain why the replacement of the glutamic acid by valine changes the way that molecules of b-globin interact with each other.
Since the valine is hydrophobic, it is attracted to the hydrophobic regions of other b-globins. This causes the hemoglobin molecules to "stick together."
Describe how the DNA code is translated into messenger RNA.
Steps of transcription (DNA gets copied into an mRNA strand in the nucleus): A gene's protein building instructions are transcribed to messenger RNA (mRNA). 1. RNA polymerase binds to DNA at a specific sequence of nucleotides called the promoter, which is where transcription begins. 2. RNA polymerase then unwinds the DNA. 3. Nucleotides are added using the rules of base pairing (remember that the A in DNA pairs with U in RNA) 4. When a specific sequence of nucleotides is reached, transcription ends. 5. The mRNA (copy of the DNA) leaves the nucleus of the cell and travels to the ribosome in the cytoplasm for translation Steps of translation (RNA is used to make a protein in the ribosome): 1. The ribosome binds to mRNA at a specific area. 2. The ribosome starts matching tRNA anticodon sequences to the mRNA codon sequence. 3. Each time a new tRNA comes into the ribosome, the amino acid that it was carrying gets added to the elongating polypeptide chain. 4. The ribosome continues until it hits a stop sequence, then it releases the polypeptide and the mRNA. 5. The polypeptide forms into its native shape and starts acting as a functional protein in the cell
Why do you think scientists call a substitution a "point mutation"? Why do you think scientists call a deletion (or an insertion) a "frameshift mutation"?
Substitution mutations (point mutations) only change one point in the RNA/DNA sequence whereas deletions and insertions (frameshift mutations) change the entire sequence from the mutation on by "shiting" the DNA sequence up (deletion) or down (insertion)
Anna has a condition called sickle cell anemia, a blood disorder. Based on the differences you observed between the normal blood slide and Anna's blood slide, what do you think is a defining feature of this disease?
The crescent shaped (sickled) red blood cells. The shape is caused by a single nucleotide substitution mutation (A to T). The change converts a glutamic acid (Glut) codon (GAG) to a valine (Val) codon (GTG).
What effect do you think the change in amino acid sequence in SCD will have on the structure of the polypeptide?
The end of the polypeptide that is normally spread out when glutamic acid is present begins to fold inward when valine is present.
What is the purpose of mitosis? What would happen if cells did not undergo mitosis?
The purpose of mitosis is cell reproduction, regeneration (healing), and growth. Mitosis is cell division that occurs in the nucleus of a cell. The result of mitosis is the formation of two cells that are genetically identical to the original cell. If cells did not undergo mitosis, there would be no life. Each person would only be the original cell that was formed at fertilization and would not be able to grow into a human.
Tay Sachs disease is caused by a mutation of one nucleotide for a protein that disrupts the activity of an enzyme in the brain. This leads to a toxic level of a substance to build up in neurons in the brain and spinal cord, leading to severe brain damage and eventually death. Why do you think that the change in one nucleotide can cause Tay Sachs disease to be fatal, whereas the change in one nucleotide causes sickle cell disease, a disease in which a person can lead a functional life?
The sickle cell mutation causes red blood cells to have a sickle shape but doesn't directly cause the symptoms associated with sickle cell disease. The blockages of the blood vessels and low number of blood vessels due to the sickled shape of the blood cells cause the symptoms and these can vary from person to person. People do not die directly from sickle cell disease, if the disease is fatal it is due to complications of the disease. The Tay Sachs mutation, however, causes the protein to not be able to do its job which always leads to a buildup of toxic substances in the brain which causes death.
What type of mutation is responsible for sickle cell disease and Tay Sachs disease?
The sickle form of the hemoglobin gene is created when an adenine nucleotide is changed to a thymine, which is a substitution/point mutation. This changes the codon for the sixth amino acid in the b-globin protein from GAG to GUG, which causes the sixth amino acid in the protein to become valine instead of glutamic acid. That single amino acid replacement in the b-globin protein alters the shape and the chemistry of the hemoglobin molecule, causing it to polymerize and distort the red blood cell into the sickle shape. Tay Sachs disease is also caused by a point mutation (one nucleotide gets changed).
Explain why a child can have sickle cell anemia even if neither parent has the disease.
This can only happen if both parents are heterozygous/carriers for the disease, meaning they have one dominant and one recessive allele (Ss). Each parent then has to pass on the recessive allele (s) to the child, giving the child the homozygous recessive genotype (ss) and, therefore, the sickle cell anemia phenotype.
Since few people with sickle cell anemia (ss) are likely to survive to have children of their own, why hasn't the recessive allele been eliminated?
because those children are now carriers
How does sickle cell disease affect daily life?
frequent doctor visits, no traveling, and high intake of water
what is the connection between genes and protein
genes are transcribed in MRNA which undergoes translation and turn into amino acids, which then joins together, to make protein (protein synthesis)
How is anemia diagnosed?
hemocrit
Why is it necessary for DNA to replicate as the first step in mitosis?
if DNA did not replicate, each new cell produced from mitosis would have half the amount of genetic information as the original cell. As the cells divide more and more, there would be less and less DNA in each cell and, very quickly, the body would not have the amount of genetic information (DNA) needed to survive.
how does a change in the DNA code affect the shape of a protein
if the dna is changed, when its transcribed into rna, the pattern will be different or wrong. This will cause the wrong amino acids to be created, which will change the shape of the protein and wont be able to function
Why is the frequency of the sickle cell allele so much lower in the United States than in Africa?
the allele mutant isn't as present in the US as it is in Africa
what is the DNA code?
the dna code/genetic code is simply the sequence of nitrogenous bases that make up the base pairs in the center of the DNA strand. Adenine, cytosine, thymine, and guanine are sequenced letter by letter, strand by strand
What is sickle cell anemia?
the lack of red blood cells
How are allele frequencies related to how a population changes over time?
those alleles may carry a life threatening disease
how are proteins produced in a cell
transcription: 1. dna unwinds, RNA polymerase binds to 1 strand where it reads the gene and makes an RNA copy of it. Pieces of RNA aren't necessary and are cut out and the product is the mRNA 2. mRNA is shipped out of the nucleus to the ribosome where it will read translation 1.ribosomes translate the mRNA into amino acids
