CONTROL OF GENE EXPRESSION

• GENE MUTATIONS

  Explain how a single base substitution causes a change in the structure of

  this polypeptide. (3)

  1.

  Change in (sequence of) amino acid(s)/primary structure;

  Reject amino acids are formed. Reject amino acids code.

  2. Change in hydrogen/ionic/disulfide bonds;

  3. Alters tertiary/30 structure;

  Reject active site. Ignore quaternary. Ignore 3D.
• • The males in Group T had thymine at nucleotide position 16 519

  • The males in Group C had a mutation resulting in cytosine at nucleotide

  position 16 519

  (a) The control regions of Group T and Group C were the same length.

  Name the type of gene mutation that is most likely to have occurred at

  nucleotide position 16 519 (1)

  Substitution
• The mutation affecting NL3 in these mice was a substitution in the

  neuroligin-3 gene.

  What is a substitution mutation? (1)


  Replacement of a base by a different base (in DNA);
• CANCER

  Scientists have found that a chemical in green tea, called EGCG, is a

  competitive inhibitor of DNMT. EGCG enables daughter cells to produce

  messenger RNA (mRNA) from the tumour suppressor gene.

  (b) Suggest how EGCG allows the production of mRNA in daughter cells. (3)

  Accept answers not rounded

  (EGCG) binds to active site of DNMT;

  2. (DNMT) cannot methylate (promoter region of tumour suppressor gene);

  3. Transcription(al) factor(s) can bind (to promoter region);

  4. RNA polymerase (stimulated/activated);

  Accept less methylation (of promoter region/tumour suppressor gene)
• A reporter who reviewed all of this work concluded that drinking green tea

  could be a cure for cancer.

  Suggest three reasons why his conclusion might not be valid. (3)

  Only investigated in throat cancer

  OR

  Might not work for other types of cancer;

  2. Not all cancers are caused by (increased) methylation (of a tumour suppressor gene)

  OR

  There are other causes of cancer;

  3. Only a significant reduction with 20/50/above 10 (μmol)

  Allow converse, ie no significant effect with 5/10 (μmol)
• Describe how alterations to tumour suppressor genes can lead to the

  development of tumours. (3)

  (Increased) methylation (of tumour suppressor genes);

  Accept abnormal methylation or hypermethylation Ignore decreased acetylation of histones

  1

  2. Mutation (in tumour suppressor genes);

  3. Tumour suppressor genes are not transcribed/expressed
• Sometimes, a mutagenic agent causes DNA to break. A different enzyme

  called ATM binds to the broken DNA. This leads to the activation of a

  protein coded for by a tumour suppressor gene. The effect of ATM binding

  is to stop cell division until DNA is repaired.

  A mutation could result in a person having non-functional forms of the gene

  that produces ATM.

  What can you predict about the possible effects of having a non-functional

  form of ATM? (3)

  1. ATM will not bind to (broken) DNA;

  2. DNA not repaired/ cell still has broken DNA;

  3. Cell division continues/tumour forms;

  4. Tumour suppressor (gene) not effective/ not

  activated;

  5. May have no effect in diploid/heterozygous

  (organism);

  6. (Which) still has a functional ATM/ATM gene;
• Define what is meant by epigenetics. (2)

  1. Heritable changes in gene function;

  2. Without changes to the base sequence of DNA;
• Explain how increased methylation could lead to cancer. (3)

  1. Methyl groups (could be) added to (both copies of) a tumour suppressor gene;

  2. The transcription of tumour suppressor genes is inhibited;

  3. Leading to uncontrolled cell division.
• Give one way in which benign tumours differ from malignant tumours. (1)

  Cells of benign tumours cannot spread to other parts of the body/metastasise

  OR

  Cells of benign tumours cannot invade neighbouring tissues;
• Explain how the methylation of tumour suppressor genes can lead to

  cancer (3)

  1. Methylation prevents transcription of gene;

  2. Protein not produced that prevents cell division / causes cell death / apoptosis;

  3. No control of mitosis.
• The doctors compared median survival times for patients in each group.

  How would you find the median survival time for a group of patients? (2)

  1. Rank all STs in ascending order;

  2. Find value with same number (of people) above and below.

  Accept find middle value
• In many trials of new drugs, a control group of patients is given a placebo

  that does not contain any drug.

  The control group in this investigation had been treated with dacarbazine.

  Suggest why they had not been given a placebo. (1)

  Not ethical to fail to treat cancer
• MM is caused by a faulty receptor protein in cell-surface membranes.

  Cells in MM tumours can be destroyed by the immune system.

  Suggest why they can be destroyed by the immune system. (3)

  1. Faulty protein recognised as an antigen / as a 'foreign' protein;

  2. T cells will bind to faulty protein / to (this) 'foreign' protein;

  3. (Sensitised) T cells will stimulate clonal selection of B cells;

  4. (Resulting in) release of antibodies against faulty protein.
• EPIGENETICS AND RNA INTERFERENCE

  One method of transferring RNAi molecules into cells involves combining

  these molecules with a lipid. Suggest why this increases uptake of RNAi

  molecules into cells(1)

  Cell/membrane has a) phospholipid bilayer
• Steroid hormones are hydrophobic.

  Explain why steroid hormones can rapidly enter a cell by passing through

  its cell-surface membrane. (2)

  1. Lipid soluble

  2. Diffuse through phospholipid bilayer
• In the cytoplasm, testosterone binds to a specific androgen receptor (AR).

  An AR is a protein.

  Suggest and explain why testosterone binds to a specific AR. (2)

  1. Has a (specific) tertiary structure/shape;

  2. (Structures are) complementary;
• Plants transport sucrose from leaves to other tissues for growth and storage.

  SUT1 is a sucrose co-transporter protein.

  Scientists investigated whether the cells of tobacco plant leaves used SUT1 to

  transport sucrose to other tissues.

  (b) To study the role of SUT1 in tobacco plants, scientists reduced the

  expression of the SUT1 gene.

  When the SUT1 gene is transcribed, the SUT1 mRNA produced is called

  'sense' SUT1 mRNA. The scientists genetically modified plants by inserting

  an extra gene so that this also allowed the production of 'antisense' SUT1

  mRNA.

  The scientists had two types of tobacco plants:

  • type A - plants that were genetically modified

  • type B - plants that were not genetically modified.

  Suggest how the production of 'antisense' SUT1 mRNA in type A plants

  would reduce the expression of the SUT1 gene. (4)


  b) 1. Antisense mRNA is complementary to 'sense' mRNA;

  2. Antisense mRNA would bind/base pair to (sense) mRNA; OR

  Double stranded (m)RNA forms;

  3. Ribosomes would not be able to bind;

  4. Preventing/less translation (of mRNA)

  OR

  Preventing/less production of SUT1 (protein);
• Scientists from the first successful drug trial to reduce concentrations of

  huntingtin (lines 9-11) reported that the drug is not a cure for Huntington's

  disease.

  Suggest two reasons why the drug should not be considered a cure.

  Do not include repeats of the drug trial in your answer. (2)

  Small sample size

  Only four-months
• Suggest and explain one way epigenetics may affect the age when symptoms of Huntington's disease start (2)

  1. (Increased) methylation of DNA/gene/allele;

  2. Inhibits/prevents transcription;

  OR

  3. Decreased methylation of DNA/gene/allele;

  4. Stimulates/allows transcription;

  OR

  5. Decreased acetylation of histone(s);

  6. Inhibits transcription;

  OR

  7. Increased acetylation of histone(s); 8. Stimulates/allows transcription;
• Scientists investigated the role of a protein called CENP-W in mitosis. Their method involved cell fractionation and ultracentrifugation.

  (a) The scientists began by lysing (breaking open) cells and organelles using a detergent that dissolves lipids in water.

  Suggest how the detergent releases CENP-W from cells. (2)

  1. Cell membranes made from phospholipid;

  2. (Detergent) dissolves membranes / phospholipid (bilayer);
• Explain how ultracentrifugation separates CENP-W from other molecules. (2)


  1. Spin (liquid / supernatant) at (very) high speed /

  high g;

  2. Molecules / CENP-W separates depending on

  (molecular) mass / size / density;
• Define what is meant by epigenetics. (2)

  1. Heritable changes in gene function;

  2. Without changes to the base sequence of DNA;
• Explain how increased methylation could lead to cancer. (3)

  1. Methyl groups (could be) added to (both copies of) a tumour suppressor gene;

  2. The transcription of tumour suppressor genes is inhibited;

  3. Leading to uncontrolled cell division.
• STEM CELLS

  Myelodysplastic syndromes (MDS) are a group of malignant cancers. In MDS, the bone marrow does not produce healthy blood cells.

  Haematopoietic stem cell transplantation (HSCT) is one treatment for MDS. In HSCT, the patient receives stem cells from the bone marrow of a person who does not have MDS. Before the treatment starts, the patient's faulty bone marrow is destroyed.

  (a) For some patients, HSCT is an effective treatment for MDS. Explain how. (3)


  1. Produce healthy blood cells

  2. No MDS cells

  3. Stem cells divide
• MDS can develop from epigenetic changes to tumour suppressor genes. In some patients, the drug AZA has reduced the effects of MDS. AZA is an inhibitor of DNA methyltransferases. These enzymes add methyl groups to cytosine bases.

  Suggest and explain how AZA can reduce the effects of MDS in some patients. (3)

  1. ( AZA ) reduces methylation ( of DNA / cytosine / gene ) ;

  2. ( Tumour suppressor ) gene is transcribed / expressed ;

  3. Prevents rapid / uncontrollable cell division OR Cell division can be controlled / stopped / slowed ;
• The control patients were treated with conventional drugs. Give two reasons why. (2)

  1. Effect of AZA can be compared;

  2. Unethical not to treat (control group);
• The scientists carried out further work to investigate how the transplanted stem cells developed after transplantation.

  • The scientists transplanted stem cells from wild type male mice into AS female mice.

  • After 20 weeks, they found that the quantity of protein in the urine of these female mice had significantly decreased.

  • They examined cells from glomeruli in the female mice. Some of these cells contained a Y chromosome.

  Suggest how the transplanted stem cells reduce proteinuria. (2)

  2. Reduce loss of protein at the glomerulus

  (Transplanted stem cells) differentiate/specialise;
• Sickle cell disease (SCD) is a group of inherited disorders. People with SCD have sickle-shaped red blood cells. A single base substitution mutation can cause one type of SCD. This mutation causes a change in the structure of the beta polypeptide chains in haemoglobin.

  Haematopoietic stem cell transplantation (HSCT) is a long-term treatment for SCD. In HSCT, the patient receives stem cells from the bone marrow of a person who does not have SCD. The donor is often the patient's brother or sister. Before the treatment starts, the patient's faulty bone marrow cells have to be destroyed.

  (b) Use this information to explain how HSCT is an effective long-term treatment for SCD.

  1.

  2.

  3.

  Produce healthy (red blood) cells

  OR

  Produce (normal) polypeptide/haemoglobin;

  Produce only healthy (red blood) cells is only equivalent to mark point 1.

  Accept produce 'normal'/non-SCD cells. Ignore type of stem cell e.g. pluripotent.

  No sickle/faulty/SCD (red blood) cells (produced)

  OR

  No defective polypeptide/haemoglobin;

  Stem/marrow cells (continuously) divide/replicate

  OR

  Less chance of rejection (from brother/sister);

  Differentiate is not equivalent to divide/replicate. Ignore type of stem cell e.g. pluripotent.
• Some scientists have concluded that this method of gene therapy will be a more effective long-term treatment for SCD than HSCT. Use all the information provided to evaluate this conclusion. (3)

  3 (For gene therapy)

  1. No destruction of bone marrow

  OR

  No destruction of stem cells;

  Accept no destruction of faulty bone marrow unless context indicates this is against gene therapy.

  2. Donors are not required;

  Stating 'only own cells used' is not equivalent.

  3. Less/no chance of rejection (own stem cells);

  (Against gene therapy)

  4. Sickle/faulty (red blood) cells still produced

  5. Immune response against genetically modified cells/virus

  OR

  Long-term effect not known (as is new treatment)

  OR

  Virus could cause side effects;

  Accept 'virus could cause problems' or 'risk(s) with virus'.
• Current research into the treatment of red-green colour blindness involves the use of induced pluripotent stem cells (iPS cells) (lines 17-19).

  Suggest how iPS cells could correct red-green colour blindness. (2)

  1. (iPS cells) divide;

  2.(iPS cells) develop/differentiate into (green

  sensitive) cones;
• The use of iPS cells could have advantages over the use of gene therapy to correct red-green colour blindness (lines 19-20).

  Using the information from the passage, suggest and explain reasons why. (3)

  1 (Use of iPS cells) long-term;

  2. (Use of iPS cells) less chance of

  rejection/immune response;

  3. (Use of iPS cells) single treatment;

  4. Harm/side effects from using viruses (in gene

  therapy);
• GENOME PROJECTS

  In Europe, viruses have infected a large number of frogs of different species. The viruses are closely related and all belong to the Ranavirus group.

  Previously, the viruses infected only one species of frog.

  (a) Suggest and explain how the viruses became able to infect other species of frog. (2)


  1.

  Mutation in the viral DNA/RNA/genome/genetic material;

  Accept named examples mutations

  2. Altered (tertiary structure of the) viral attachment protein;

  Accept 'antigen' for 'attachment protein' Accept causes antigenic variability

  3. Allows it/attachment protein/virus to bind (to receptors of other species);

  Accept descriptions of binding eg is complementary
• Name two techniques the scientists may have used when analysing viral DNA to determine that the viruses were closely related. (1)

  • The polymerase chain reaction

  • Genetic/DNA fingerprinting

  • (Gel) electrophoresis

  • DNA/genome sequencing;
• Determining the genome of the viruses could allow scientists to develop a vaccine.

  Explain how. (2)

  1. (The scientists) could identify proteins (that derive from the genetic code) OR (The scientists) could identify the proteome; 2. (They) could (then) identify potential antigens (to use in the vaccine);
• Describe how the B lymphocytes of a frog would respond to vaccination against Ranavirus.

  You can assume that the B lymphocytes of a frog respond in the same way as B lymphocytes of a human

  Do not include details of the cellular response in your answer. (3)

  1. B cell (antibody) binds to (viral) specific/complementary receptor/antigen;

  2. B cell clones

  OR

  B cell divides by mitosis;

  3. Plasma cells release/produce (monoclonal) antibodies (against the virus);

  4. (B/plasma cells produce/develop) memory cells;
• What is meant by a genome? (1)

  all the DNA in a cell/organism
• Explain why the antibody binds to the transcription factor. (2)


  1. (Transcriptional factor/antibody) has a

  specific/tertiary structure/shape;

  2. Complementary (shape/structure);
• Use the chart to explain what 'precipitated DNA' consists of. (1)

  DNA, transcription factor and antibody;
• DNA PROBE AND GEL ELECTROPHORESIS

  Plants transport sucrose from leaves to other tissues for growth and storage. SUT1 is a sucrose co-transporter protein.

  Scientists investigated whether the cells of tobacco plant leaves used SUT1 to transport sucrose to other tissues.

  (a) The scientists used a radioactively labelled DNA probe to show that the cells of tobacco plant leaves contained the SUT1 gene.

  Describe how they would do this.

  Do not include PCR in your answer. (4)

  1.

  Extract DNA and add restriction endonucleases/restriction enzymes;

  (b) 1.

  2. Separate fragments using electrophoresis;

  3. (Treat DNA to) form single strands

  OR

  (Treat DNA to) expose bases;

  Ignore method used to separate strands

  4. The probe will bind to/hybridise/base pair with the SUT1/gene;

  5. Use autoradiography (to show the bound probe);