DNA probes & genetic screening

Cystic fibrosis (CF) is a recessive inherited disorder caused by a defective CFTR gene.

Table 6 shows the number of people with CF and the estimated population of the UK in 2020 and 2022.

Calculate how many more people had CF than was expected in 2022.

You can assume the relative frequency of CF in a population remains constant.

Show your working.

Additional number of people

CF can be caused by a three-base deletion mutation in the CFTR gene. This deletion

creates a recessive allele called F508del.

DNA probes and gel electrophoresis were used to screen two parents and their two children for the F508del allele. One of the children was diagnosed with CF.

Figure 5 shows the results.

What is a DNA probe?

The identity of each family member can be determined from the relative position of the bands shown in Figure 5.

Use information in Figure 5 to:

• complete Table 7

• explain how you identified the child with CF.

You can use F to represent the dominant CFTR allele and f to represent the recessive F508del CFTR allele.

Leigh syndrome (LS) is a rare, recessive, inherited condition.

LS is caused by a mutation in any one of more than 75 different genes coding for proteins involved in oxidative phosphorylation.

In 80% of people with LS, these mutations occur in nuclear DNA. In 20% of people with LS, these mutations occur in mitochondrial DNA (mtDNA).

15% of the nuclear DNA mutations that cause LS occur in the SURF1 gene. A mutated SURF1 gene codes for a shorter polypeptide than a non-mutated SURF1 gene.

Name one type of SURF1 gene mutation and explain how this mutation could lead to production of a shorter polypeptide.

Globally, the frequency of LS is 1 in 40 000

In the Faroe Islands, which are 18 isolated islands, the frequency of LS is 1 in 1700

The population of the Faroe Islands is 49 053

Estimate the number of people in the Faroe Islands with LS caused by a mutation in the SURF1 gene.

Use information in this question and the information on page 12.

Give your answer to the nearest whole number.

Show your working.

The frequency of LS is higher in the Faroe Islands than globally.

Suggest and explain one reason why.

LS usually causes death within the first three years of life.

Using all the information in this question, evaluate whether all people should be genetically screened for LS.

BRCA1 and BRCA2 are human genes that code for tumour suppressor proteins. Mutations in BRCA1 and BRCA2 can cause cancer (lines 1–2). Explain how.

Genetic testing, using DNA from saliva, can screen for all known harmful mutations in both genes (lines 5–6). Describe how this DNA could be screened for all known harmful mutations in both genes.

Effective treatment of ER-positive breast cancers often involves the use of drugs which have a similar structure to oestrogen (lines 9–10).

Suggest and explain how these drugs are an effective treatment of ER-positive breast cancers.

Blood tests can be used to test for cancers (line 11). However, the results of blood tests may not be conclusive when testing for prostate cancer. Explain why.

Treatment with drugs might be able to reverse the epigenetic changes that cause cancers (lines 16–17). Suggest and explain how.

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.

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.

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.

The scientists hypothesised that lower rates of sucrose transport from leaves would cause reduced growth.

To test this hypothesis, the scientists provided leaves of type A and type B plants with labelled carbon dioxide (¹⁴CO₂). To estimate sucrose transport out of leaves, they measured the percentage of¹⁴C remaining in the leaves for 16 hours.

Figure 5 shows their results.

Calculate the ratio of percentage of¹⁴C remaining in leaves of type B to type A plants 16 hours after providing¹⁴CO₂

In type B plants, the percentage of¹⁴C remaining in the leaves does not reach zero per cent, as shown in Figure 5.

Suggest two reasons why.

1

2

The scientists measured physiological differences between type A plants and

type B plants.

Table 3 shows the scientists’ results as they presented them.

Sucrose is able to inhibit the production and activity of rubisco in leaves of a plant. Type A plants have decreased dry mass compared with type B plants.

Use all the information to suggest and explain how the physiological factors in Table 3 would contribute to the decreased dry mass observed in type A plants.

Turn over for Section B

Section B

one question.

You are advised to spend no more than 45 minutes on this section.

What is a DNA probe?

DNA probes are used to detect specific base sequences of DNA.

The process is shown in Figure 6.

Describe how the DNA is broken down into smaller fragments.

The DNA on the nylon membrane is treated to form single strands. Explain why.

A scientist used DNA probes and electrophoresis to screen four volunteers for five different viral DNA fragments.

Figure 7 shows the results the scientist obtained. The lanes numbered 2 to 5 represent the four volunteers.

Lane 1 of Figure 7 enabled the size of the different viral fragments to be determined.

Suggest and explain how.

The lengths of the viral DNA fragments were:

• 600 base pairs

• 250 base pairs

• 535 base pairs

• 300 base pairs

• 500 base pairs.

Which volunteers had at least one of the viral DNA fragments with 250 base pairs or 535 base pairs?

Alzheimer’s disease (AD) is a non-reversible brain disorder that develops over a number of years. At the start of 2014 the number of Americans with AD was estimated to be 5.4 million. Every 30 seconds another person in America develops AD.

In the brain of a person with AD there is a lower concentration of acetylcholine. 5 This affects communication between nerve cells and initially results in memory loss and confusion. Some of the symptoms of AD that are associated with communication between nerve cells are reduced by taking the drug donepezil. Donepezil inhibits the enzyme acetylcholinesterase.

A gene mutation called E280A found on chromosome 14 causes early-onset AD 10 at a mean age of 49 years. The age at which the E280A mutation is expressed to cause AD varies.

Yaramul is a town in a historically isolated region of the Andes Mountains. The population of this town has the highest frequency of the E280A mutation in the world. The origin of the E280A mutation in this population has been traced back 15 to a common ancestor in the 17th century. Natural selection has not reduced the frequency of the E280A mutation in the population.

This autosomal dominant mutation involves a change in triplet 280 from GAA to GCA. Scientists analysed chromosome 14 from 102 individuals from Yaramul. They recorded a sample size of 204 and detected 75 E280A mutations but only 20 74 potential AD cases. The scientists identified individuals with the mutation by whole genome sequencing. They had decided that a DNA probe would not be a suitable method to detect the E280A mutation.

Assuming no one with AD died in 2014, calculate the annual percentage increase in AD cases in America for 2014 (lines 2–4).

Explain how donepezil could improve communication between nerve cells (lines 7–9).

Suggest and explain two reasons why there is a high frequency of the E280A mutation in Yaramul (lines 13–15).

Explain why natural selection has not reduced the frequency of the E280A mutation in the population (lines 16–17).

The age at which the E280A mutation is expressed to cause AD can vary (lines 11 – 12).

Suggest and explain one reason for this.

One scientific study which analysed chromosome 14 involved 102 individuals. The scientists recorded a sample size of 204. In this sample they detected 75 E280A mutations but only 74 potential AD cases (lines 19 – 21).

Suggest explanations for the figures the scientists recorded.

Suggest why a DNA probe for the mutated triplet was not considered a suitable method for detection of the E280A mutation (lines 22–23).