DNA probes and genetic screeningAQA A-Level Biology: Revision notes

Individuals of the same species have almost identical DNA, but there are differences in base sequence, for example different alleles of a gene, mutated alleles and differences in non-coding DNA. These differences can be used to identify individuals and to diagnose heritable conditions, for example cystic fibrosis, Huntington's disease and some cancers.

A DNA probe is a short, single-stranded piece of DNA with a base sequence complementary to part of a target allele. It is labelled so it can be detected: a radioactive label (detected by darkening of x-ray film) or a fluorescent label (detected by fluorescence). Probes can be made for any allele whose sequence is known.

Probes are used to locate specific alleles of genes, including mutated alleles that cause disease.

1. Extract DNA from the patient's cells (for example blood or cheek cells) and, if needed, make copies with PCR and cut it into fragments.
2. Heat to break the hydrogen bonds between the strands, giving single-stranded DNA.
3. Add the labelled probe. If the target allele is present, the probe forms hydrogen bonds with its complementary sequence: DNA hybridisation.
4. Wash off unbound probe.
5. Detect the label. A signal means the allele is present.

Labelled probes are used to screen patients for:

• Heritable conditions, for example to find carriers of a recessive allele such as cystic fibrosis, or to test an embryo or fetus.
• Drug responses: alleles that change how a person absorbs, activates or breaks down a drug.
• Health risks: alleles that raise the risk of diseases such as breast cancer (BRCA1 and BRCA2).

A positive result shows that the allele is present. It does not always mean the person will develop the condition.

Genetic counselling gives people information and support. A counsellor explains what a result means, calculates the probability that children will inherit an allele (for two carriers of a recessive allele, 1/4 affected, 1/2 carrier), describes options, and helps people make their own informed decisions.

Personalised medicine uses a patient's genotype to choose the drug and dose most likely to work, so treatment is more effective and side effects are reduced.

Worked example: two carriers (Ff × Ff). Probability of an affected child = 0.25; both of two children affected = 0.25 × 0.25 = 0.0625.

Benefits: earlier diagnosis and treatment, preventive action, informed family planning, and better drug choice.

Drawbacks: anxiety; a positive result is not certainty; a negative result may give false reassurance; cost, especially if few people carry the allele; privacy, insurance and employment concerns; implications for relatives; and difficult decisions about pregnancy.

When given data, quote and compare the figures, for example the risk with and without the allele, and the proportion of people who carry it. End with a justified conclusion.