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

Sickle cell anemia is a disease caused by certain mutations of 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 what type of mutations are seen in sickle cell anemia. 

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

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

Figure 1

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

One mutation causing sickle cell anemia was originally only found in one population in central Africa. It is now found in many different populations across Asia and Africa. Suggest how the spread of this mutation may have occurred.

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 that can cause a characteristic facial appearance, developmental delays and hyperactivity. FG syndrome is more prevalent in males, suggest why.

Describe what is meant by an inversion mutation.

Suggest the effect of an inversion mutation on the functionality of the protein produced.

Gene mutations occur spontaneously. State the part of the cell cycle when gene mutations are most likely to occur and give an explanation for your answer. 

The Mormon faith was founded in 1840 by Lynman Hinman. The mormon community are highly polygamous, with most men having at least three wives. 80% of the current population in Shortcreek, USA are blood descendants of the town’s founders Joseph Jessop and John Barlow. The community is also very secular with interbreeding only occurring within the community. 

One small Morman town in Hildale, Utah was recently reported to have 20 cases of a rare genetic condition caused by fumarase deficiency leading to severe neurological problems. The disease is recessive and extremely rare with the usual risk being 1 in 400 million. The risk of inheriting the disease in Utah is 1 in 500. 

Use the information provided to calculate the current Mormon population of Hildale, Utah. 

The faulty allele that causes fumarase deficiency is the result of a mutation of a gene called FH. This mutation leads to the production of a protein that is missing one amino acid compared to individuals without the mutation.

Suggest how the mutation leads to the production of a protein that has one amino acid missing.

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

Suggest how producing a fumarase protein with one less amino acid may lead to a disease such as the one found in the Mormon community of Hilldale.

Mutations such as the one seen in fumase deficient patients are usually caused by an error during DNA replication. Name the enzyme that is responsible for ensuring the DNA sequence is correct. 

Fetal haemoglobin is the dominant form of haemoglobin used and produced by a fetus as it grows within its mothers womb. Fetal haemoglobin is made from two alpha chains, the same as those in adult haemoglobin, and two gamma chains unique to this protein.

The genes for gamma and beta haemoglobin are both found close to each other on chromosome 11 in humans. Researchers sequenced the DNA coding for gamma and beta haemoglobin chains and found the sequences were very similar. Both the gamma and beta genes have 438 coding nucleotides. 

Calculate how many amino acids make up a beta or gamma chain.

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 changed 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.

There are several ways in which genes can become mutated.

Which statement(s) in Table 1 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, how many tumour cells will be present after 8 weeks?

Give your answer in standard form.

Give three factors that increase the chances of genetic mutation.

Explain why the effect of a substitution mutation may have less of an impact than a deletion mutation.

Identify the type of mutation that would result in the protein formed in Figure 1, 

Cystic fibrosis is a mutation caused by the deletion of one amino acid from the CFTR protein. The CFTR protein forms a channel which moves negatively charged chloride ions across the cell membrane. Cystic fibrosis sufferers lack these CFTR channels which means chloride ions cannot be transported out of the cell.

A symptom of cystic fibrosis is the production of thick sticky mucus, which blocks airways and causes persistent coughing. Increased mucus also increases susceptibility to infections of the lung.

Explain how this mutation to the CFTR gene would lead to a cystic fibrosis sufferer lacking effective CFTR protein channels.

With reference to water potential gradients, suggest how a mutation of the CFTR gene may lead to the symptoms described in part (c). 

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

Figure 1

A study was completed to compare cigarette consumption to death rates due to lung cancer amongst males and females from 1900 to 2010. The results of this study are represented in the graph in Figure 2. 

Figure 2

The scientist 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 might provide an advantage to organisms.

Look at the base codes in Table 1 and identify the type of mutation shown on the mRNA, provide an explanation for your choice.

Table 1

Table 2 shows the different combinations of bases on the mRNA and the amino acids which they code for. The amino acid names have been abbreviated; for example, ‘Gly’ stands for the amino acid Glycine.

Table 2

Use Table 2 to explain what effect 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 amino acids that will be correct?

The Philadelphia chromosome is a mutated version of chromosome 22, found to contain a gene usually found on chromosome 9 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 BCR gene from chromosome 22. This fusion gene is shown to increase activity of tyrosine kinase, an enzyme which is 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 explain how they might increase the occurrence of genetic mutations.