HSC Exam Practice

Sample response. Genetic screening is testing carried out to identify a genetic condition or a raised risk of one before symptoms appear. It is detection rather than genetic engineering because it only reads existing genetic or biochemical information: no DNA sequence is added, removed or altered, so the genotype remains exactly as it was and is still heritable.

Marking notes. 1 mark for defining screening as identifying a condition or risk before symptoms. 1 mark for the explicit contrast that no DNA is altered. Do not award the second mark for "it does not treat the patient", which is a different point.

Sample response. In phenylketonuria a mutation in the PAH gene leaves phenylalanine hydroxylase missing or non-functional, so phenylalanine from dietary protein cannot be converted to tyrosine and accumulates in the blood and brain, where high concentrations damage developing neurons. A low-phenylalanine diet started in the first weeks removes the substrate the broken pathway cannot handle, keeping blood phenylalanine below the toxic range so the child develops normally. The DNA is untouched: both faulty alleles remain and are still passed on. What has been prevented is the phenotype, not the genotype.

Marking notes. 1 mark for the mechanism, that phenylalanine accumulates because the enzyme is inactive, and is neurotoxic. 1 mark for explaining that the diet removes the substrate so the toxic accumulation does not occur. 1 mark for the explicit genotype-versus-phenotype distinction, that the allele is unchanged and still heritable.

Sample response. PGT is selection because embryos created through IVF are biopsied at the blastocyst stage, around day 5, using cells from the trophectoderm, and their DNA is tested; embryos without the variant are then identified and transferred. No embryo's DNA is altered at any point, so the technique chooses between existing genotypes rather than changing one. Two limitations: the family's exact variant must already be known in advance, so PGT cannot help with an unidentified or de novo variant; and it requires a full IVF cycle with its cost and physical burden, producing a limited number of embryos which may all be affected. Accept also the ethical limitation about which conditions justify selection.

Marking notes. 1 mark for the selection-not-modification point, ideally with the biopsy or transfer detail. 1 mark per valid limitation (maximum 2).

Sample response. Somatic editing changes DNA in body cells such as liver, retina or blood stem cells. Those cells are not the ones that become sperm or eggs, so nothing changed can be inherited: the patient may be cured while their children face exactly the same risk they always did. It is legally permitted in Australia, and approved somatic therapies include Casgevy, Luxturna and Zolgensma. Germline editing changes DNA in gametes or a very early embryo, so the change appears in every cell of the resulting person, including their own gametes, which makes it heritable and passes it permanently into the population. It is the only genetic intervention that could remove an allele from a family line, and it is illegal in Australia: the Prohibition of Human Cloning for Reproduction Act 2002 makes it an offence to implant a genetically modified embryo.

Marking notes. 1 mark for the cells changed in each case, correctly contrasted. 1 mark for heritability correctly assigned to each. 1 mark for legal status of both, permitted versus prohibited. 1 mark for the consequence that somatic editing is treatment rather than prevention of inheritance, or for naming the 2002 Act.

Sample response. Carriers of a recessive allele are heterozygous, and one working copy of the gene is enough to produce sufficient functional protein, so carriers are perfectly healthy and show no phenotype. An affected child appears only when two carriers of the same allele have children together, which gives a one in four chance in every pregnancy. Because the allele can therefore pass silently through many generations without producing an affected individual, most carriers have no family history at all. The implication is that family history is an unreliable way to identify who is at risk, so reproductive carrier screening must be offered to prospective parents generally rather than only to those with a known family history. In Mackenzie's Mission roughly one in twenty people screened carried a variant for at least one of cystic fibrosis, spinal muscular atrophy or fragile X syndrome.

Marking notes. 1 mark for explaining that one functional copy is sufficient, so carriers are unaffected. 1 mark for the consequence that the allele passes silently, so family history misses most carriers. 1 mark for the screening implication, that screening should be offered generally rather than targeted by family history.

Sample response. NIPT is a screening test: it analyses cell-free fetal DNA in the mother's blood from about 10 weeks, carries no procedure-related miscarriage risk, and is highly sensitive for trisomy 21, 18 and 13, but it reports a raised chance rather than a diagnosis, so a positive result still needs confirming, and it does not detect most single-gene or structural abnormalities. Amniocentesis is a diagnostic test: fetal cells are sampled from amniotic fluid at about 15 to 20 weeks and karyotyped or sequenced, giving a definitive result for chromosomal and single-gene disorders, but it carries a procedure-related miscarriage risk of about 0.5%. In practice NIPT is done first because it is early and carries no procedural risk, so it can be offered to everyone to flag at-risk pregnancies; amniocentesis then confirms a positive NIPT result or is offered where family history or other indications warrant it. The choice is therefore a trade-off between procedural risk, diagnostic certainty and timing.

Marking notes. 2 marks for NIPT correctly characterised (screening, sample, timing, no procedural risk, needs confirmation). 2 marks for amniocentesis correctly characterised (diagnostic, sample, timing, about 0.5% risk, detects single-gene disorders too). 1 mark for an explicit comparative judgement explaining the sequencing of the two tests as a risk, certainty and timing trade-off. A response that describes both tests without comparing them caps at 4.

Sample response. The claim has two parts and both are flawed, although it contains one legitimate concern.

The 1 in 4 figure is the expected probability that any one child of two carriers of the same autosomal recessive allele is affected. It applies independently to every pregnancy, so it does not mean one child in four of that couple's children will be affected, and a previous unaffected child does not reduce the risk in the next pregnancy. For the 25 couples identified, this is a substantial and lifelong risk of a serious condition, not a marginal one.

The "waste of money" reasoning misunderstands why the yield is low. Carriers of a recessive allele are heterozygous and healthy, because one working copy produces enough functional protein, so the allele passes silently through generations and most carriers have no family history. That is precisely why screening must be offered broadly rather than targeted: there is no way to find the 25 couples without testing the 10,000. About one in twenty individuals screened carried a variant for at least one condition, so the information is far from rare even though both-carrier couples are.

The claim that screening "prevents nothing" confuses detection with modification. It is true that screening alters no DNA. What it enables is an informed decision, supported by non-directive genetic counselling that explains the inheritance pattern, the numerical risk and every available option. Those options may include PGT-M within an IVF cycle to select embryos without the variant, prenatal diagnosis, preparation for early management where effective treatment exists, or a decision to proceed without further testing. The benefit therefore comes from the action the information enables, not from the test itself, which is the same reasoning that applies to any screening program.

A genuine limitation: the screening covers only three specific conditions, so a negative result does not mean no genetic risk of any kind, and this can create false reassurance. Accept also: broad genetic testing returns variants of uncertain significance, which cause anxiety without an actionable decision; the follow-on options such as IVF with PGT are expensive and concentrated in major cities, so equity of access limits who can act on a positive result; or that the modelled figure of 34 cases avoided depends on assumptions about how many couples change their reproductive decisions.

Marking notes. 1 mark for correctly explaining the 1 in 4 as a per-pregnancy probability. 1 mark for stating that it does not mean one in four of a couple's actual children, or that prior children do not change it. 1 mark for explaining why the low yield is unavoidable, that healthy carriers have no family history. 1 mark for rejecting "prevents nothing" by distinguishing detection from modification. 1 mark for identifying at least two concrete options the information enables. 1 mark for naming non-directive counselling as the mechanism that converts a result into a decision. 1 mark for one valid limitation.

Sample response outline. Judgement. The statement is an oversimplification. Prevention is increasingly achievable for specific, known single-gene conditions, but "entirely preventable" ignores multifactorial disease, legal limits, equity barriers and unresolved technical problems.

Gene therapy and CRISPR. Approved therapies are genuine but narrow. A viral vector, usually an adeno-associated virus, delivers a working gene copy to one accessible tissue: Luxturna injects under the retina for RPE65 retinal dystrophy, and Zolgensma delivers SMN1 intravenously for spinal muscular atrophy, working only if given before motor neurons are lost. CRISPR-Cas9 uses a guide RNA complementary to the target sequence to carry Cas9 to that site, where it cuts both strands and the cell's repair produces the edit. Casgevy, the first approved CRISPR medicine, treats sickle cell disease and beta-thalassaemia by editing the patient's own blood stem cells outside the body to switch fetal haemoglobin back on. Crucially it is somatic, so it does not prevent inheritance: the patient's children face the same risk. Off-target effects, where the guide binds a similar sequence and Cas9 cuts the wrong gene, and mosaicism, where an edited embryo becomes a patchwork of edited and unedited cells, remain unsolved. Costs of roughly 2.5 million dollars per dose confine these to small numbers of patients.

PGT. PGT-M is effective where the family's variant is already known. Within an IVF cycle, trophectoderm cells are biopsied at the blastocyst stage and tested, and unaffected embryos are transferred. It is selection, never modification. Limits: the variant must be known in advance, a full IVF cycle is required with its cost and physical burden, the number of embryos is limited and all may be affected, and there is genuine ethical debate about which conditions justify selection.

Screening programs. These are the most broadly effective element. Newborn bloodspot screening tests for more than twenty conditions at 48 to 72 hours, and works precisely where early treatment succeeds and late treatment does not: PKU is prevented as a phenotype by a low-phenylalanine diet while the genotype is unchanged. Reproductive carrier screening finds couples at one-in-four risk who would be missed by family history, since carriers are healthy. Prenatal NIPT and amniocentesis enable detection but not prevention in themselves; what follows depends on decisions the family makes with non-directive counselling.

Scientific limits. The largest limit is biological rather than technical: Type 2 diabetes, cardiovascular disease and most cancers are multifactorial, with dozens or hundreds of variants each contributing small risk and environment doing much of the rest, so there is no single gene to select against or edit. These conditions, which represent most of the disease burden, remain the territory of prevention campaigns. De novo chromosomal disorders also cannot be addressed by gene therapy. Broad testing frequently returns variants of uncertain significance, producing anxiety without an actionable decision.

Ethical and legal limits. Germline editing is the only intervention that would make a change heritable, and it is prohibited in Australia under the Prohibition of Human Cloning for Reproduction Act 2002, because consent is impossible from a person who does not yet exist, off-target changes would be inherited, and the effects cannot be recalled. The 2018 case in China drew international condemnation and a prison sentence. Further ethical dimensions include reproductive autonomy, which is why counselling is non-directive; disability perspectives on which conditions should be selected against; the risk of genetic discrimination; and equity, since IVF with PGT costs thousands per cycle and gene therapies millions per dose, both concentrated in major cities.

Conclusion. Genetic prevention is real, expanding and specific. It is strongest for known single-gene risks through screening and selection, weaker and narrower through somatic engineering, legally closed for heritable change, and structurally unable to address the multifactorial diseases that dominate the burden. "Entirely preventable" is therefore not supportable.

Marking notes. 2 marks for gene therapy and CRISPR, including at least one named example and the somatic-does-not-prevent-inheritance point. 2 marks for PGT and screening programs correctly characterised as selection and detection with at least one limitation each. 2 marks for scientific limits, requiring the multifactorial argument plus one other. 2 marks for ethical and legal dimensions, requiring the Australian prohibition on germline editing plus at least one substantive ethical issue such as consent, autonomy, discrimination or equity. An explicit judgement is required for full marks in the top band.

Band guidance. Band 6 sustains the detection, selection and modification distinction throughout, uses cautious accurate wording, and qualifies its judgement precisely. Band 5 covers all three technologies with limitations but treats ethics as a separate list. Band 4 describes the technologies without distinguishing what each can biologically achieve, or claims genetic disease will soon be eliminated.