Differences in DNA between individuals of the same species can be exploited
AQA
A-Level
A DNA probe is a short, single-stranded DNA fragment with a base sequence complementary to the target allele. It carries a label, such as a radioactive phosphorus-32 tag detected on X-ray film, or a fluorescent tag visible under UV light. To locate an allele, the sample DNA is first amplified by PCR. It is then heated to break hydrogen bonds, making it single-stranded. The labelled probe is added and the mixture cooled. If the target allele is present, the probe binds to its complementary sequence via hydrogen bonding—this is DNA hybridisation. Finally, unbound probes are washed away, and the label's presence is detected to locate the specific allele.
13
Objectives
10
Exam Tips
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Pitfalls
21
Key Terms
21
Mark Points
Subtopics in this area
The use of labelled DNA probes and DNA hybridisation to locate specific alleles of genes.
The use of labelled DNA probes that can be used to screen patients for heritable conditions, drug responses or health risks.
The use of this information in genetic counselling and personalised medicine.
Students should be able to evaluate information relating to screening individuals for genetically determined conditions and drug responses.
Differences in DNA between individuals of the same species can be exploited Revision Guide
Learning Objectives
What you need to know and understand
- Describe, in order, how a labelled DNA probe is used to locate a specific allele in a sample of DNA.
- Explain why the sample DNA must be amplified and made single-stranded before hybridisation.
- Describe how a bound probe is detected, naming a suitable label and the method used to see it.
- Describe how labelled DNA probes are used to screen a patient's fixed DNA for specific alleles.
- Explain why a separate complementary probe is needed for each allele, and what a negative result therefore does and does not prove.
- Describe one use of screening for each of a heritable condition, a drug response and a health risk, naming a specific example for each.
- Explain what a genetic counsellor provides to a couple who both carry a recessive allele, including how risk is calculated.
- Describe how knowing a patient's alleles changes the choice of drug or dose prescribed.
- Distinguish personalised medicine from gene therapy by stating what each one changes.
- Evaluate a screening programme for genetically determined conditions by giving benefits, limitations and a justified conclusion.
- Evaluate the use of screening for drug responses to improve treatment efficacy and reduce adverse reactions.
- Explain why a positive screening result may be a false positive and why a negative result does not guarantee absence of risk.
- Suggest an ethical consequence of genetic screening and state who is affected by it.
Marking Points
Key points examiners look for in your answers
- one mark for using PCR to amplify the DNA sample before testing
- one mark for heating the DNA to break hydrogen bonds and make it single-stranded
- one mark for adding a labelled DNA probe that binds to the target allele by complementary base pairing
- one mark for washing away unbound probes so only hybridised probes remain
- one mark for detecting the allele using fluorescence under UV light or radioactivity on X-ray film
- State that a DNA probe is a short, single-stranded DNA sequence labelled with a fluorescent or radioactive tag.
- Explain that a probe is complementary to a specific allele and binds to it by complementary base pairing.
- Describe that patient DNA is amplified by PCR, made single-stranded, and fixed to a membrane before labelled probes are added.
- Explain that unbound probes are washed off, and a signal shows the patient carries the allele detected by the bound probe.
- Give a named application for each category: identifying carriers of a heritable condition such as cystic fibrosis; detecting a drug-response allele such as a CYP2C19 variant affecting clopidogrel activation; and detecting a health-risk allele such as BRCA1.
- Explain that a separate complementary probe is needed for each allele, so a negative result shows only that the tested alleles were not detected.
- one mark for genetic counselling providing information about the risk of passing on a condition to enable an informed decision
- one mark for calculating the probability of an affected child using a pedigree or genetic diagram
- one mark for personalised medicine matching a specific drug or dose to an individual's DNA genotype
- one mark for explaining that this prevents harmful side effects or avoids prescribing ineffective treatments
- one mark for a valid DNA-based example, such as testing TPMT alleles to adjust azathioprine dosage
- One mark for a benefit of screening, such as early detection allowing preventative treatment or increased monitoring before symptoms develop.
- One mark for explaining that screening for inherited alleles affecting drug responses can guide effective dosages and reduce adverse reactions.
- One mark for stating that screening detects only known mutations, so a negative result does not completely rule out the condition.
- One mark for explaining that in multifactorial conditions a risk allele raises probability rather than guaranteeing disease, because environmental factors contribute.
- One mark for recognising that false positives cause unnecessary anxiety or treatment, and false negatives give false reassurance.
Examiner Tips
Expert advice for maximising your marks
- 💡Always name the label and how it is detected: fluorescence under UV light or radioactivity on X-ray film.
- 💡Use the term 'hybridisation' explicitly when describing the probe binding to the target DNA.
- 💡Use the specification wording 'labelled DNA probes': state that the probe carries the label and binds to fixed patient DNA.
- 💡Always link the screening result to its application, such as choosing the correct drug dose or identifying a carrier.
- 💡For a negative result, state what it does and does not prove: only the alleles tested were not detected, not that no mutation exists.
- 💡When asked for a drug-response example, name a specific gene variant and the drug it affects, rather than describing drug response in general terms.
- 💡Use the phrase 'informed decision'—counselling questions focus on providing information, not dictating choices.
- 💡For personalised medicine, explicitly mention how differing alleles affect drug metabolism or enzyme shape.
- 💡Structure evaluation answers with points for, points against, and a justified conclusion tied to the provided data.
- 💡Use the words probability and risk rather than cause when writing about multifactorial conditions.
Common Mistakes
Pitfalls to avoid in your exam answers
- stating the probe is just 'complementary' without explicitly saying it binds or hybridises to the DNA
- forgetting that the sample DNA must be heated to become single-stranded before the probe can bind
- leaving the probe unlabelled in descriptions, meaning there is no way to detect where it has bound
- Stating that the patient DNA is labelled when describing the use of labelled DNA probes. Correction: the specification refers to labelled DNA probes, so describe the probes as carrying the label and binding to fixed patient DNA.
- Treating a positive result for a health-risk allele such as a BRCA1 mutation as a definite diagnosis of cancer. Correction: state that it indicates increased probability, not certainty.
- Assuming one probe detects all mutations. Correction: state that each allele requires its own complementary probe, so a negative result only rules out the alleles tested.
- Confusing a drug-response allele with a health-risk allele. Correction: a drug-response allele affects how a patient metabolises or responds to a medicine, whereas a health-risk allele is associated with increased probability of a condition.
- stating the counsellor makes medical decisions for the patient, rather than providing information for an informed choice
- using protein-level tests (like ER-positive breast cancer) as examples of DNA-based personalised medicine, instead of specific alleles
- confusing personalised medicine with gene therapy; personalised medicine selects treatments based on alleles, while gene therapy alters them
- Listing only advantages when the command word is evaluate; marks for limitations must also be included to access full credit.
- Writing that a screening test 'tells you whether you will get the disease' for multifactorial conditions, instead of stating it increases risk or probability.
- Using somatic tumour markers (like HER2) as examples of screening individuals for inherited genetic conditions, rather than inherited alleles like TPMT or BRCA1.