Alteration of the sequence of bases in DNA can alter the structure of proteins (A-level only)
Pearson-like Pancytopenia (PLP) is a rare, recessive, inherited condition.
PLP is caused by a mutation in any one of several genes involved in mitochondrial translation.
In 75%75\%75% of people with PLP, these mutations occur in nuclear DNA. In 25%25\%25% of people with PLP, these mutations occur in mitochondrial DNA (mtDNA).
15%15\%15% of the nuclear DNA mutations that cause PLP occur in the MRPL12 gene. A mutated MRPL12 gene codes for a shorter polypeptide than a non-mutated MRPL12 gene.
Name one type of MRPL12 gene mutation and explain how this mutation could lead to the production of a shorter polypeptide.
Globally, the frequency of PLP is 1 in 60,000. In a specific isolated valley community, the population is 80,000 and the frequency of PLP is 1 in 1,000.
Estimate the number of people in this valley community with PLP caused by a mutation in the MRPL12 gene. Show your working.
The frequency of PLP is higher in this valley community than globally. Suggest and explain one reason why.
Chloroplast DNA (cpDNA) is a circular DNA molecule found in chloroplasts. In a certain crop plant, it is 135,000 base pairs long and contains genes as well as non-coding control regions.
Plant physiologists investigated whether a single nucleotide mutation in a control region of cpDNA in soybean plants affected their resilience to drought stress.
- Plant Group A\textbf{A}A had Adenine at nucleotide position 45,200.
- Plant Group G\textbf{G}G had a mutation resulting in Guanine at nucleotide position 45,200.
The control regions of Group A\textbf{A}A and Group G\textbf{G}G were the same length.
Name the type of gene mutation that is most likely to have occurred at nucleotide position 45,200.
Group A\textbf{A}A and Group G\textbf{G}G were subjected to a 4-week water-deficit (drought) treatment. The scientists measured:
- Net photosynthetic rate (PnP_nPn).
- D1 protein abundance (a chloroplast-encoded polypeptide essential for Photosystem II function).
They calculated the percentage decrease in these measurements for both groups at the end of the 4 weeks compared to the start.
Figure 1 and Figure 2 show their results.
A student concluded from Figure 1 and Figure 2 that drought stress has a more severe damaging impact on Photosystem II and photosynthesis in Group G\textbf{G}G than in Group A\textbf{A}A.
Evaluate the student's conclusion.
The cpDNA control region is non-coding but stimulates both cpDNA replication and the transcription of chloroplast messenger RNA (mRNA).
Use this information to suggest two reasons why the mutation at position 45,200 in Group G\textbf{G}G could lead to the larger decrease in D1 protein level seen in Figure 2.
Chronic granulomatous disease (CGD) is an inherited immunodeficiency disorder. Patients with CGD have a defective NADPH oxidase enzyme complex in their phagocytic cells (such as neutrophils), preventing them from producing reactive oxygen species to kill engulfed pathogens.
A single base substitution mutation in the CYBB CYBB\,CYBB gene (which codes for the gp91-phox subunit of the NADPH oxidase complex) can lead to CGD by altering the structure of this polypeptide.
Explain how a single base substitution in the CYBB CYBB\,CYBB gene leads to a change in the tertiary structure of the gp91-phox subunit. Do not include details of transcription and translation in your answer.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a long-term treatment for CGD. In this procedure, the patient receives healthy hematopoietic stem cells from the bone marrow of a matched compatible donor. Prior to transplantation, the patient undergoes myeloablative conditioning, where chemotherapy or radiation is used to completely destroy their own faulty bone marrow cells.
Explain how HSCT acts as an effective, long-term treatment for CGD.
An alternative treatment under development is autologous ex vivo gene therapy using a modified lentiviral vector to insert a functional copy of the CYBB CYBB\,CYBB gene.
Some immunologists argue that this lentiviral gene therapy is a superior long-term treatment for CGD compared to allogeneic HSCT. Evaluate this claim using the provided information and your biological knowledge.
Colorectal cancer is a malignancy of the large intestine. Tigatuzumab is a monoclonal antibody drug designed to treat colorectal cancer by binding specifically to a cell-surface death receptor called DR5, which initiates apoptosis (programmed cell death).
A mutation in the gene SMAD4SMAD4SMAD4 leads to a non-functional transcription factor, which significantly reduces the expression of DR5 on the surface of colorectal cancer cells. Scientists measured the median percentage of cancer cells destroyed by Tigatuzumab in patients who had the SMAD4SMAD4SMAD4 mutation and those who did not.
The scientists' results are shown in Table 1.
Table 1
| Patient Group | Median percentage of cancer cells destroyed by Tigatuzumab |
|---|---|
| In patients with SMAD4SMAD4SMAD4 mutation | 14 |
| In patients without SMAD4SMAD4SMAD4 mutation | 42 |
Patients with this colorectal cancer subtype have approximately 7.5×1077.5 \times 10^77.5×107 cancer cells per cm3\text{cm}^3cm3 of tumor tissue.
Use the median values in Table 1 to calculate the difference between the number of cancer cells per cm3\text{cm}^3cm3 destroyed by Tigatuzumab in patients with the wild-type gene (without the mutation) and those with the mutant SMAD4SMAD4SMAD4 gene.
Express your answer in standard form. Show your working.
Beta-thalassemia is an inherited blood disorder. People with severe beta-thalassemia produce abnormal β\betaβ-globin polypeptide chains, resulting in unstable hemoglobin and severe anemia. A single base substitution mutation in the HBB gene on chromosome 11 is a common cause of this disorder.
Explain how a single base substitution in the HBB gene causes a change in the tertiary structure of the β\betaβ-globin polypeptide. Do not include details of transcription and translation in your answer.
Hematopoietic stem cell transplantation (HSCT) is a long-term treatment for beta-thalassemia. In standard HSCT, the patient receives blood-forming stem cells from the bone marrow of a healthy, compatible donor (such as a sibling). Before the transplant, the patient's own faulty bone marrow stem cells must be completely destroyed using high-dose chemotherapy (myeloablation). Use this information to explain how HSCT is an effective long-term treatment for beta-thalassemia.
A newer treatment option for beta-thalassemia involves the use of ex vivo gene therapy, as shown in the diagram below.
Some scientists have concluded that this method of gene therapy is a more effective long-term treatment for beta-thalassemia than traditional HSCT. Use all the information provided to evaluate this conclusion.
Multiple myeloma is a cancer of plasma cells (a type of white blood cell). Daratumumab is a monoclonal antibody drug used to treat multiple myeloma by binding to a surface protein called CD38 and initiating cell destruction.
A mutation in the gene XBP1XBP1XBP1 leads to a non-functional transcription factor, which reduces the production of CD38 on plasma cells. Scientists determined the median percentage of plasma cells destroyed by Daratumumab in multiple myeloma patients who had the XBP1XBP1XBP1 mutation and those who did not.
The scientists' results are shown in Table 1.
Table 1
| Patient Group | Median percentage of plasma cells destroyed by Daratumumab |
|---|---|
| In patients with XBP1XBP1XBP1 mutation | 8 |
| In patients without XBP1XBP1XBP1 mutation | 33 |
Multiple myeloma patients have approximately 4.0×1084.0 \times 10^84.0×108 plasma cells per dm3\text{dm}^3dm3 of blood.
Use the median values in Table 1 to calculate the difference between the number of plasma cells per dm3\text{dm}^3dm3 destroyed by Daratumumab in patients with the wild-type gene (without the mutation) and those with the mutant XBP1XBP1XBP1 gene.
Express your answer in standard form. Show your working.
In a species of Antarctic icefish (Chaenocephalus aceratus), tolerance to extreme cold is enhanced by an antifreeze glycoprotein. A mutant allele, FMF^MFM, is formed due to a 48 base-pair deletion from the wild-type allele, FWF^WFW. The glycoprotein coded for by the mutant allele FMF^MFM is 312 amino acids long.
Calculate the percentage reduction in the size (number of amino acids) of the protein coded for by the mutant allele FMF^MFM compared with the protein coded for by the wild-type allele FWF^WFW. Give your answer to 3 significant figures and show your working.
Pyruvate kinase deficiency is an inherited metabolic disorder in humans caused by mutations in the PKLR PKLR\,PKLR gene. This gene encodes the enzyme pyruvate kinase, which is vital for maintaining ATP production via glycolysis in red blood cells.
Define the term gene mutation and explain how a mutation in the PKLR PKLR\,PKLR gene can:
- have no effect on the primary structure of the encoded pyruvate kinase polypeptide
- lead to a non-functional enzyme that reduces the survival rate of red blood cells.
Laroque syndrome (LS) is a rare, recessive, inherited condition.
LS is caused by a mutation in any one of several genes involved in peroxisome biogenesis.
In 75%75\%75% of people with LS, these mutations occur in nuclear DNA. In 25%25\%25% of people with LS, these mutations occur in mitochondrial DNA (mtDNA).
15%15\%15% of the nuclear DNA mutations that cause LS occur in the PEX11B gene. A mutated PEX11B gene codes for a shorter polypeptide than a non-mutated PEX11B gene.
Name one type of PEX11B gene mutation and explain how this mutation could lead to the production of a shorter polypeptide.
Globally, the frequency of LS is 1 in 100,000. In a specific isolated fjord community, the population is 64,000 and the frequency of LS is 1 in 800.
Estimate the number of people in this fjord community with LS caused by a mutation in the PEX11B gene. Give your answer to the nearest whole number. Show your working.
The frequency of LS is higher in this fjord community than globally. Suggest and explain one reason why.
Sena syndrome (SS) is a rare, recessive, inherited condition.
SS is caused by a mutation in any one of several genes involved in mitochondrial translation.
In 80%80\%80% of people with SS, these mutations occur in nuclear DNA. In 20%20\%20% of people with SS, these mutations occur in mitochondrial DNA (mtDNA).
12%12\%12% of the nuclear DNA mutations that cause SS occur in the MRPS16 gene. A mutated MRPS16 gene codes for a shorter polypeptide than a non-mutated MRPS16 gene.
Name one type of MRPS16 gene mutation and explain how this mutation could lead to the production of a shorter polypeptide.
Globally, the frequency of SS is 1 in 50,000. In a specific isolated island group, the population is 54,000 and the frequency of SS is 1 in 1,600.
Estimate the number of people in this island group with SS caused by a mutation in the MRPS16 gene. Give your answer to the nearest whole number. Show your working.
The frequency of SS is higher in this island group than globally. Suggest and explain one reason why.
Alteration of the sequence of bases in DNA can alter the structure of proteins (A-level only) Questions
Practise AQA A Level Biology Alteration of the sequence of bases in DNA can alter the structure of proteins (A-level only) with exam-style questions for A Level Biology. 17 questions covering Alteration of the sequence of bases in DNA can alter the structure of proteins (A-level only), matched to the AQA A Level Biology (7402) specification and written in Paper 1, Paper 2 and Paper 3 style. Every question includes a full worked solution and mark scheme, so you can see where marks are awarded rather than just whether you got the answer right.