HSC Exam Practice

Sample response. A somatic mutation occurs in a body cell and affects the individual but is not normally inherited by offspring. A germ-line mutation occurs in a gamete or in the gamete-producing cell lineage and can be passed to offspring at fertilisation.

Marking notes. 1 mark for somatic = body cell, not inherited; 1 mark for germ-line = gamete / gamete-producing lineage, inherited.

Sample response. Coding DNA is the part of a gene that is translated into the amino acid sequence of a protein; a mutation in coding DNA can alter codons and so directly change the protein (e.g. silent, missense, nonsense or frameshift changes). Non-coding DNA is not translated into protein but includes regulatory elements such as promoters, enhancers and splice sites; a mutation in non-coding regulatory DNA may not change the protein sequence but can alter when, where or how strongly a gene is expressed.

Marking notes. 1 mark for defining coding DNA + consequence (codon / amino acid change); 1 mark for defining non-coding DNA + naming an example of a regulatory element; 1 mark for identifying that the non-coding consequence is at the level of expression / regulation, not amino acid sequence.

Sample response. A skin cell is a body cell, so a mutation that occurs in it is a somatic mutation. Somatic mutations are confined to the affected tissue (and its derivatives, e.g. metastases) and are not present in the patient's gametes. Because only mutations carried by gametes can be passed at fertilisation, the melanoma's mutations cannot be inherited by the patient's children.

Marking notes. 1 mark for identifying skin cell as a body cell (somatic); 1 mark for stating mutation is not present in gametes; 1 mark for linking lack of inheritance to the requirement that mutations be in the germ-line to be passed to offspring.

Sample response. First, non-coding DNA includes regulatory elements such as promoters and enhancers, and a mutation there may change when, where or how strongly a gene is expressed (gene expression / regulation). Second, non-coding DNA also includes splice sites and regulatory RNA genes; a mutation can disrupt RNA processing or regulatory RNA function. Both routes can change phenotype even though no amino acid sequence has been altered.

Marking notes. 1 mark for naming a non-coding regulatory mechanism (e.g. promoter / enhancer / transcription factor binding) and its effect on expression; 1 mark for a second mechanism (splice site / regulatory RNA / RNA processing); 1 mark for explicitly stating that phenotype can change without altering protein sequence.

Sample response. Where in the body the mutation occurs (somatic vs germ-line) determines whether it can be inherited and so whether it is population-relevant. Where in the genome it occurs (coding vs non-coding) determines whether it changes the amino acid sequence of a protein directly or instead changes how a gene is regulated. Because these two dimensions are independent, the full significance of a mutation requires both questions to be answered together; one mutation can be somatic + coding (affects the individual at protein level), another germ-line + non-coding (heritable, alters regulation), and so on.

Marking notes. 1 mark for the inheritance dimension (somatic vs germ-line) and what it controls; 1 mark for the functional-location dimension (coding vs non-coding) and what it controls; 1 mark for explicitly stating that both dimensions are independent and both required.

Sample response (a). Somatic mutation burden decreases from melanoma (~14 mutations/Mb), to lung in smokers (~8), to colorectal (~3), to childhood ALL (~0.6). There is roughly a 23-fold difference between the highest and lowest cancer types.

Sample response (b). Melanoma develops in skin cells that are directly exposed to UV radiation; UV is a strong mutagen that produces pyrimidine dimers and characteristic C→T substitutions, so somatic mutations accumulate at a high rate. Childhood ALL arises in blood-cell precursors that have undergone relatively few divisions and very little mutagen exposure, so the somatic burden is much smaller. The difference reflects exposure to mutagens, not a difference in heritability.

Sample response (c). The mutations in the melanoma are somatic — they occur in skin cells (body cells), not in the patient's gametes. Only germ-line mutations are passed to offspring at fertilisation. Therefore the tumour's mutations cannot be inherited by the patient's children, and testing for "the same mutations" in children is misdirected. Separate, inherited risk variants (e.g. germ-line CDKN2A) are a different test for a different question.

Marking notes. Part (a) — 1 mark for stating direction (decreases) AND ranking the cancers correctly; 1 mark for citing at least one specific data value. Part (b) — 1 mark for naming UV as the mutagen and linking to melanoma; 1 mark for contrasting with ALL's low exposure/division rate; 1 mark for emphasising mutagen exposure as the explanation. Part (c) — 1 mark for identifying the tumour mutations as somatic; 1 mark for explaining that only germ-line mutations are inherited and so distinguishing tumour mutations from inherited risk alleles.

Sample response (a). The mutation is in non-coding DNA. The stimulus locates the single base change 60 bp upstream of the gene, inside the promoter, and explicitly states that the coding sequence is unchanged — promoters are regulatory elements that are not translated, so they are by definition non-coding.

Sample response (b). The student's claim is wrong. Although the protein sequence is unchanged, the promoter mutation reduces transcription factor binding to ~25% of normal, which reduces mRNA output to ~25% and therefore reduces the amount of functional protein produced. Phenotype depends on whether enough functional protein is available, not only on its amino acid sequence. This is exactly the lesson's Card 3 point that non-coding regulatory mutations can change when, where or how strongly a gene is expressed and so still be biologically significant.

Marking notes. Part (a) — 1 mark for identifying non-coding; 1 mark for justifying from the stimulus (promoter location + unchanged coding sequence). Part (b) — 1 mark for rejecting the claim; 1 mark for linking reduced binding to reduced mRNA / protein quantity; 1 mark for explaining that phenotype depends on amount of functional protein, not only its sequence, with reference to the regulatory-DNA principle.

Sample response. The claim that mutation significance depends only on whether the amino acid sequence of a protein is changed is false: it captures one important dimension but ignores a second, independent dimension that determines whether a mutation matters at all to the next generation. Mutation significance depends on (i) where in the body the mutation occurs — somatic vs germ-line — and (ii) where in the genome it occurs — coding vs non-coding. The protein-sequence claim only addresses part of (ii). A somatic coding mutation, for example a UV-induced thymine-dimer mutation in a skin-cell tumour-suppressor gene, can drive melanoma in the individual; the amino-acid sequence has changed, the lesion is significant for the patient, but it ends with the individual and is not population-relevant because it is not in the germ-line. A germ-line coding mutation, for example a BRCA1 missense substitution inherited from a parent, also changes amino-acid sequence, but because it is in every cell including gametes it is inherited and enters the gene pool — significance now spans both the individual and the population. The coding/protein-sequence framing breaks down completely when we consider non-coding mutations. A somatic mutation in the TERT promoter (~70% of cutaneous melanomas) does not change a single amino acid in the TERT protein, yet it reactivates telomerase expression in adult skin cells and contributes directly to tumour growth. A germ-line mutation in a non-coding enhancer upstream of the LCT gene (lactase persistence) similarly leaves the lactase protein sequence unchanged, but keeps the gene expressed into adulthood — a heritable, population-spread phenotype. Both refute the claim because both alter phenotype by changing gene expression rather than protein sequence. The defensible position is therefore the lesson's two-dimensional rule: a mutation's significance depends on its inheritability (somatic vs germ-line) and on whether it changes the protein directly or instead changes regulation. The original claim is rejected because it considers only one half of the second dimension and ignores the first dimension entirely.

Marking notes. 1 mark — Explicitly rejects the claim and frames mutation significance as a two-dimensional question (inheritance × functional location). 1 mark — Defines or accurately applies somatic vs germ-line. 1 mark — Defines or accurately applies coding vs non-coding. 1 mark — Provides a valid named coding-mutation example with classification (e.g. UV-induced skin-cell tumour-suppressor mutation; inherited BRCA1 missense). 1 mark — Provides a valid named non-coding-mutation example with classification (e.g. somatic TERT promoter mutation in melanoma; germ-line lactase-persistence enhancer variant). 1 mark — Explains specifically why a non-coding mutation can change phenotype without altering protein sequence (via regulation / expression / promoter / enhancer mechanism). 1 mark — Reaches an explicit evaluative judgement that integrates both dimensions and rejects the protein-only criterion in precise lesson terminology (somatic, germ-line, coding, non-coding, regulation, gene pool, population relevance).