Genetic Mutations (A Level only) (AQA A Level Biology)

Sickle cell anemia is a disease caused by mutations in the gene coding for β-haemoglobin. Table 1 shows part of the DNA base sequence coding for β-haemoglobin and two mutations of this sequence.

Table 1

Complete Table 1 with the DNA sequences that are transcribed to produce β-haemoglobin, mutant 1 and mutant 2.

Table 2 shows some examples of amino acids, their structures and the mRNA codons that code for them. 

Table 2

i) Assuming that the sequence in Table 1 is given in-frame, state the type of mutation seen in sickle cell anaemia. 

ii) Explain the effect of mutation 1 and mutation 2 on the protein that is produced in each case. 

Sickle cell anaemia causes aggregation of the mutated haemoglobin proteins which changes the shape of red blood cells, as seen in Figure 1. This affects red blood cell function. 

Figure 1

State the function of red blood cells that would be affected by sickle cell anaemia and explain why the shape of white blood cells is not affected by the disease. 

FG syndrome is a rare genetic disorder caused by an inversion mutation in the MED12 gene on the X chromosome. FG syndrome is a recessive disorder.

FG syndrome is more prevalent in males. Explain why this is the case.

Define the term inversion mutation.

Suggest the effect of an inversion mutation on the functionality of the protein for which the affected gene codes.

Gene mutations occur spontaneously.

State the part of the cell cycle during which gene mutations are most likely to occur and explain your answer. 

Fumarase deficiency is caused by a mutation in a gene called FH. This mutation leads to the production of a protein that is missing one amino acid.

Suggest how the mutation could result in production of a protein that has one amino acid missing.

Fumarase is an enzyme that converts fumarate (4C) into malate (4C) in the Krebs cycle. 

Suggest how a shortened fumarase protein, as described in a), may cause an individual to show symptoms of a genetic disorder.

Mutations, such as the one seen in fumerase-deficient patients, are usually caused by an error during DNA replication.

Name the enzyme that is responsible for ensuring that the new DNA sequence is correct.

The protein haemoglobin is made up of polypeptide chains known as globin chains. Adult haemoglobin contains two alpha chains and two beta chains.

Researchers sequenced the DNA coding for beta globin chains and found that it contains 438 coding nucleotides. 

Calculate the number of amino acids that make up a beta chain.

Fetal haemoglobin is the dominant form of haemoglobin present in a fetus as it grows. Fetal haemoglobin contains two alpha chains, as well as two gamma globin chains that are unique to this protein.

The genes for gamma and beta globin are found close to each other on chromosome 11 in humans.

Originally humans only had one haemoglobin gene on chromosome 11. Suggest how a fetal version of the gene evolved.

β-thalassemia is a genetic disease caused by a mutation in the beta haemoglobin gene. One of the causes of β-thalassemia is two adenine nucleotides being removed from codon 8 of the beta hemoglobin gene. One of the major effects of this deletion is that codon 21 changes from CAG to UAG.

 Figure 1

Using Figure 1 and your knowledge of deletion mutations, suggest how this mutation affects the protein that is produced.

For someone to suffer with β-thalassemia they must have two mutated beta haemoglobin alleles. State the type of the genotype that causes the β-thalassemia phenotype.

Different mutations have different effects on an organism.

Give the letter that corresponds to the statement(s) in Table 1 that correctly describes the effect of a mutation in the exon of a gene.

Table 1

Chronic myeloid leukemia (CML) is a type of cancer that affects white blood cells. CML is caused when a section of chromosome 9 breaks off and fuses with chromosome 22.

Name the type of mutation that occurs in chronic myeloid leukemia.

A type of malignant tumour cell divides every 6 hours.

Starting with one malignant tumour cell, and assuming none die, calculate the number of tumour cells that will be present after 8 weeks. Give your answer in standard form.

Give three factors that increase the chances of genetic mutation.

Explain why a substitution mutation may have less of an impact on phenotype than a deletion mutation.

Figure 1 shows a normal protein (left) and a protein synthesised from a mutated form of a gene (right).

Describe the mutation that would result in the protein formed from the mutated gene.

Figure 1

Cystic fibrosis is a disorder caused by the deletion of one amino acid from the CFTR protein. The functional CFTR protein forms a channel which allows the movement of negatively charged chloride ions across cell membranes.

Explain how this mutation in the CFTR gene leads to the development of disorder symptoms.

A symptom of cystic fibrosis is the production of thick, sticky mucus which blocks airways and causes persistent coughing.

With reference to water potential gradients, suggest how mutated CFTR proteins in the membranes of cells lining the airways may lead to the symptoms described. 

Identify the type of mutation shown in Figure 1 and explain its effect on the resulting protein.

Figure 1

A study compared cigarette consumption to death rates from lung cancer amongst males and females between 1900 - 2010. The results of this study are presented in Figure 2. 

Figure 2

A student concluded that cigarette consumption was a key factor influencing death rates due to lung cancer over this period.

Use Figure 2 to evaluate this claim.

In a second study it was found that, on average, there is one DNA mutation per lung cell for every 50 cigarettes smoked. 

The analysis found that people who smoke a pack of 20 a day for a year generate 160 mutations per lung cell, 110 per larynx cell, 45 per pharynx cell, 25 per bladder cell and 5 per liver cell.

Calculate the number of mutations a person would experience per year if they reduced the number of cigarettes they smoked by 20%.

Explain how a carcinogen, such as tobacco, can lead to the formation of lung cancers.

Explain why the degeneracy of the genetic code provides an advantage to organisms.

Look at the base codes in Table 1 and identify the type of mutation shown on the mRNA. Explain your choice.

Table 1

Table 2 shows the different combinations of mRNA bases and the amino acids for which they code.

Table 2

Use Table 2 to explain the effect that the mutation identified in part (b) would have on the protein formed.

You have an RNA transcript that is 135 nucleotides long. A frameshift mutation occurs at the 101st nucleotide. 

Calculate the number of correct amino acids that will be present in the mutated protein.

The Philadelphia chromosome is a mutated version of chromosome 22 that contains a gene usually located on chromosome 9. The gene is called the ABL gene. 

Figure 1

Identify the type of mutation which forms the Philadelphia chromosome and suggest why it may have a significant impact on the phenotype of the organism.

The Philadelphia mutation creates a fusion gene which is a combination of the ABL gene from chromosome 9 and the BCR gene from chromosome 22. This fusion gene has been shown to increase activity of tyrosine kinase, an enzyme involved in the switching on and off of many cellular functions, including cell division.

Suggest how the Philadelphia mutation could result in the production of a large number of immature lymphocytes.

In America 0.5 % of all cancer cases are diagnosed as acute lymphoblastic leukemia. 80 % of those cases are in children. In 2019 there were 1,762,400 diagnosed cancer cases in America. 

Calculate the number of children diagnosed with acute lymphoblastic leukemia in 2019.

Identify two mutagenic agents and suggest how they might increase the rate of genetic mutation.