Genetic Technology Applied to Medicine (CIE A Level Biology)

BRCA1 and BRCA2 are genes that code for proteins involved with the repair of DNA mutations

State how mutations occur in DNA.

[1]

Suggest how mutations in BRCA1 and BRCA2 genes could increase the likelihood of tumour development.

[3]

Individuals with a family history of breast cancer will often have genetic screening to identify mutations in the BRCA1 and BRCA2 genes.

Outline how genetic screening can reduce the risk of breast cancer in high risk individuals.

Fig. 1 shows a genetic screening technique.

Fig. 1

Use Fig. 1 to suggest how a DNA probe can be used to show the presence of a particular allele.

Screening for BRCA1 and BRCA2 is carried out in adults, but some other genetic traits are tested for in foetuses prior to birth. In either case the results can bring up difficult decisions and individuals considering or undergoing such screening will often receive help from a genetic counsellor to help them think through ethical and social issues.

Outline the social and ethical issues around genetic screening.

Adult haemoglobin is a protein made up of four polypeptide chains; two alpha chains and two beta chains. 

Beta thalassemia is a genetic condition in which a mutation in the gene for the beta chain of adult haemoglobin either reduces or prevents its production.

Suggest three symptoms of beta thalassemia.

A form of gene therapy is being trialled for use in the treatment of beta thalassemia. The treatment involves harvesting stem cells from the bone marrow of patients before altering them in the lab and infusing the cells back into the patient's body. 

Describe the stem cells found in bone marrow.

[2]

Outline the process by which the stem cells can be altered.

[3]

One difficulty with carrying out safe and effective gene therapy is of ensuring that any new DNA is inserted into the right part of a patient's DNA.

Suggest why the insertion of DNA in the wrong location could be a problem.

Give three other concerns related to gene therapy.

Adenosine deaminase (ADA) is an enzyme involved with multiple chemical reactions inside cells. One effect of ADA deficiency is a lack of lymphocyte maturation.

Outline how ADA deficiency can lead to severe combined immune deficiency (SCID).

Treatment options for SCID caused by an ADA deficiency include:

• Enzyme replacement therapy (ERT), in which patients receive injections of recombinant ADA enzymes.
• Haemoatopoietic stem cell transplant (HSCT), in which patients receive a bone marrow transplant from a donor.

Complete the table below by suggesting an advantage and a disadvantage of each of these treatment types.

More recent treatment for ADA SCID involves the use of gene therapy.

Describe the process of gene therapy for ADA SCID.

Human Factor VIII is a protein required for the process of blood clotting. Recombinant human clotting factor VIII (rhFVIII) can be produced in the kidney or ovary cells of hamsters.

Suggest how rhFVIII can be produced using hamster cells.

Before the production of rhFVIII, factor VIII protein was extracted from the blood of human donors.

State two advantages of producing rhFVIII rather than extracting factor VIII from human blood.

Recent research has shown that it is possible to produce rhFVIII using human embryonic kidney (HEK) cells. Scientists believe that this could be advantageous because the post-translational modifications that take place in hamster cells are different to those that occur in human cells. rhVIII produced in human cells would therefore be identical to factor VIII produced by fully developed humans.

Suggest what might happen to proteins during post-translational modification.

[2]

Suggest why it is preferable to produce factor VIII that is identical to that produced by fully developed humans.

[1]

rhFVIII is essential for the treatment of haemophilia, a genetic condition in which non-functioning factor VIII means that blood does not clot.

Haemophilia is caused by a mutation in a gene located on the X chromosome. The dominant F allele codes for normal factor VIII while the mutated f allele codes for non-functioning factor VIII.

A male with haemophilia has a child with a heterozygous woman. Give the phenotype probabilities for their children.

The polymerase chain reaction (PCR) is used to produce large quantities of DNA from a very small original sample. The main steps of one PCR method are shown in Fig. 1.

Fig. 1

Explain why it is necessary to heat the mixture to 95 °C (step 1).

[2]

(ii)

Explain why primers are included in the mixture.

[2]

(iii)

Explain why the enzyme Taq polymerase, rather than any other type of DNA polymerase, is used in PCR.

[2]

The presence of a faulty allele of the gene BRCA2 can lead to an increased chance of developing breast cancer. There are many different faulty alleles of the gene BRCA2.

People who are considered to be at risk of breast cancer may choose to be tested for the presence of these alleles in their genomes.

A microarray can be used to test blood samples for the presence of these alleles. The microarray contains DNA probes for different faulty alleles of the BRCA2 gene.

(i)

State the meaning of the term genome.

 [1]

(ii)

Suggest which type of cell from a blood sample is suitable for testing for the presence of these faulty alleles.

   Give a reason for your choice.

[1]

(iii)

Outline how faulty alleles of the BRCA2 gene can be detected using the microarray.

[4]

(iv)

Outline the advantages of screening for faulty alleles of the BRCA2 gene.

[4]

Huntington's disease is an inherited condition that affects brain function. It is described as a progressive disease as it gets worse over time. The mutation that causes Huntington's disease involves a DNA segment known as a CAG trinucleotide repeat. Normally, the CAG segment is repeated 10 to 35 times within the gene. In a person who has inherited the allele for Huntington's disease there can be 30 to 180 repeats within the gene. 

Scientists studied the allelic profile of CAG repeats in 65 individuals affected by Huntington's disease. There results are shown in the graph below.

Fig. 1

Individuals can be tested to see if they have an allele for the gene carrying more than 35 CAG repeats. The scientists suggest that their data can be used to predict the age that the individual will develop Huntington's disease. 

Use the information provided in the question and the graph in Fig. 1 to evaluate this suggestion. 

The allele for Huntington's disease is inherited from parent to offspring. Huntington's disease is always fatal.  

Use the data from the graph in Fig. 1 to suggest why Huntington's is present in the population despite its fatality. 

Huntington's disease is caused by a single faulty gene (HTT) that codes for the protein Huntingtin. The repeated CAG segments leads to the production of an abnormally long version of the huntingtin protein which is cut into smaller, toxic fragments that bind together in neurones called medium spiny neurones, disrupting the normal functions of these cells. In vivo gene therapy has shown promise as a possible treatment for Huntington's disease.

Outline how in vivo gene therapy may be used to treat Huntington's disease. 

A couple are planning to start a family and wants to undergo genetic screening to assess their risk of passing on Huntington's disease to their unborn children.

Discuss the benefits of genetic screening in the context of Huntington's disease.