Mutations & Gene Editing (HL IB Biology)

It is currently believed that about 5% of the human genome has been conserved for more than 200 million years and only 8.2% of the human genome is functional (coding) DNA.

Define a conserved sequence.

Scientists have several different theories about the existence of conserved sequences that are shared between several different species. 

Explain two hypotheses for the existence of highly conserved sequences.

The table below includes estimated mutation rates of different species per generation. 

Identify the DNA with the fastest mutation rate.

[1]

Calculate the percentage difference between the mutation rate of the mtDNA and the Paramecium tetraurelia.

[2]

The human genome DNA mutation rate is quite similar to that of the DNA virus.

Explain why the mutation rate of the virus is considered to be a lot faster than that of human DNA. 

[2]

Human genome mutation rate varies between the types of gametes. It is higher in sperm cells than in egg cells. 

Suggest a reason for this difference. 

[2]

Compare and contrast germ line mutations and somatic cell mutations.  

[3]

Marfan syndrome is an autosomal dominant genetic disorder that affects the connective tissue. This disorder is caused by mutations in the fibrillin 1 gene (FBN1), which is found on chromosome 15. There are 1300 different mutations that are known to alter the expression of this gene. 

The diagram below shows the effects of two different mutations of the DNA on the base sequence of the mRNA. The table shows the mRNA codons for four amino acids.

State the type of gene mutation represented by mutation 2.

Explain how mutation 1 and 2 may affect the fibrillin protein for which this section of DNA is part of the code.

[2]

Scientists have discovered that there are new mutations of the FBN1 gene and that mutagens in the environment may have contributed to these mutations.

List three examples of mutagenic agents that may have caused these mutations.

A study into the genetics of Marfan syndrome found that a nonsense mutation that should have caused a significant shortening of the polypeptide coded for by FBN1 gene actually only had a very small impact due to a self-correcting mechanism in the cell called 'exon skipping', specifically of exon 51. 

Suggest a possible mechanism for 'exon skipping' and explain why this would be useful in the cell. 

Leber Congenital Amaurosis (LCA)  is a term given to a group of diseases that are caused by mutations in at least 25 genes. These diseases are all related to vision loss and blindness as the mutations all affect the functioning of the retina in the eye. It is often expressed in young children.

One of these genes is called CEP290. When functioning, this gene codes for a protein in the retina and helps to transport proteins in photoreceptor cells to aid with vision. If someone inherits two mutated copies of this gene then they are not able to produce this protein, and this causes them to have LCA10 and vision loss which could ultimately result in blindness if left untreated. 

The most common form of mutation in CEP290 is called a splice mutation. 

The way that this mutation works is that an area of non-coding intron DNA is mutated to turn some of that genetic code into a "cryptic" exon. This means that the non-coding DNA is incorrectly translated and the resulting protein has an additional section of amino acids that results in a non-functioning protein. 

A type of therapy for this condition is in clinical trials. This is called EDIT-101 and uses gene editing to cut this section of DNA from the affected cells. 

The gene editing method in EDIT-101 uses CRISPR technology.

Outline the function of the following molecules in this process:

Cas9

[1]

sgRNA (guide RNA)

[1]

Other than the mechanism described above, suggest two other possible outcomes of a mutation at a site on the DNA that controls splicing.

In the EDIT-101 procedure, a virus is loaded with the sgRNA and the Cas9 and then a small amount of this virus is inserted into the back of each of the patient's eyes using a syringe.

Describe the sequence of events that occurs after the patient has been injected with the sample. 

In a 2024 study, 12 adults and 2 children were injected with EDIT-101 in order to test for adverse side-effects and to identify if the treatment worked to improve patient vision. 

Suggest a reason why so few people participated in this trial. 

[2]

Nine participants experienced a "meaningful improvement" in their vision following the trial and zero participants experienced "serious" adverse side-effects from the treatment.

Explain why it may not be the case that the EDIT-101 medicine can immediately be rolled out to a much larger number of patients. 

[3]

One mark is available for clarity of communication throughout this question.

Compare and contrast the X and Y chromosome.

The sex of a foetus is determined by the father.

Explain this statement.

Outline how a substitution mutation can alter the amino acid sequence of a polypeptide by using sickle cell anaemia as an example.

Wilson's disease is a condition caused by a mutation of gene ATP7B located on chromosome 13, which codes for an ion transport enzyme. This enzyme is responsible for transporting copper ions (Cu²⁺) into bile so that it can be removed from the body through the digestive tract. There are several mutations which may lead to Wilson's disease; one of these mutations involves the replacement of the amino acid histidine by glutamine.

Describe the type of mutation that could have led to this disease.

Based on the information provided in part a), explain the effect this mutation would have on the transport of copper ions.

In most cases of Wilson's disease, a sufferer must have two copies of the mutated ATP7B allele before the disease is present.

Suggest what this may indicate about the dominance of the ATP7B allele.

People suffering from Wilson's disease have high levels of free copper in their bloodstream which have been shown to cause damage to the cell membranes of red blood cells.

Explain the consequences of this to the sufferer.

The following diagram shows a section of mRNA containing five codons. 

The triplets of bases in a DNA molecule that codes for some of the amino acids are listed in the table below.

Identify the amino acid sequence on this section of the mRNA molecule, using the information in the diagram and table.

The five codons in the diagram at part a) are near the start of the sequence coding for a polypeptide. A mutation led to the deletion of one of the bases from codon 3.

Explain the possible consequences of this mutation.

Guanine (G) in codon 4 changed to adenine (A) due to a mutation.

Describe the effect this mutation would have on the amino acid sequence in the diagram of part a).

[1]

Explain your answer.

[1]

The following diagram shows a section of a polypeptide, indicating the polarity of the amino acid R-groups.

Describe the possible interactions that could contribute to the tertiary structure of this polypeptide, by using the information in the diagram.

Duchenne muscular dystrophy (DMD) is a genetic disorder that leads to the degeneration of muscle tissue over time due to changes in a protein called dystrophin.

Dystrophin is a rod-shaped protein that acts as a link connecting actin filaments in muscle fibres to the extracellular matrix by attaching to a protein complex (DAPC) located in the sarcolemma.

Dystrophin is coded for by the DMD gene, and the complete protein consists of four domains (N-terminal, Rod, Cys-domain and C-terminal), as shown in the diagram below.

The following diagram shows the regions of the DMD gene that codes for the different domains of dystrophin.

One of the causes of Duchenne muscular dystrophy is a substitution mutation that leads to the formation of a stop codon in the rod domain of the DMD gene.

Explain the impact this mutation would have on the resulting dystrophin protein by using the information in the diagrams.

After transcription of the DMD gene, the pre-mRNA measures about 2.1 megabases (Mb) while the mature mRNA consists of about 14 kilobases (kb). Note that 1 Mb = 10³ kb.

Calculate the percentage decrease in size of the mRNA molecule after modification. Show your working and give your answer to three significant figures.

Dystrophin contains many hydrophobic regions that plays an important role in maintaining its structure. Some of the mutations leading to DMD replaces amino acids within the hydrophobic regions with ones containing polar or charged R-groups.

Suggest the effect that this would have on the structure of dystrophin.

Hereditary transthyretin (hATTR) amyloidosis is an inherited condition that is caused by a mutation of a gene that codes for the blood protein transthyretin.

This mutation results in the protein forming clumps in different areas of the body, such as the cardiovascular system, digestive system and around nerve fibres.

Certain drugs that are designed to bind to mRNA molecules are used as treatment for this condition.

Suggest why these drugs could be used as a treatment for hATTR.

The table below shows the genetic code and the amino acids that it codes for.

Use the information in the diagram and table to describe the effect the mutation would have on transthyretin.

Mitochondrial diseases (MD) are a group of genetic disorders where body cells cannot aerobically respire properly.

One example of an MD is caused by the mutation of a mitochondrial gene that codes for a tRNA molecule. The mutation leads to the replacement of a guanine base with adenine in the anticodon of the tRNA molecule. This results in the formation of a non-functional protein in the mitochondrion.

Suggest how the change in the anticodon of a tRNA molecule leads to an MD.

Explain the role of ATP in translation.

Edwards syndrome is a rare but serious condition that influences birth weight and development. Death rates during infancy are high. The image below shows the karyogram of an individual with Edwards syndrome.

Use the karyogram to suggest the cause of Edwards syndrome.

[1]

Describe the events that have led to the feature noted in part i).

[2]

Edwards syndrome affects every cell in the body.

Explain why this is the case.

One of the life-threatening complications that babies with Edwards syndrome can be born with is a structural abnormality in the heart. The image below shows a heart abnormality that can be seen in babies born with Edwards syndrome.

Explain why the abnormality shown in the image can be life-threatening.

The graph below shows the number of pregnancies affected by Edwards syndrome between 1985 and 2008.

In the year marked X there were 1 100 000 pregnancies, and in the year marked Y there were 700 000 pregnancies.

Calculate the number of affected pregnancies at the times marked X and Y.

[2]

Suggest one reason for the difference in affected pregnancies between times X and Y.

[1]