DNA Sequencing and DNA Profiling

Q1 — Sample Band 6 response (7 marks), annotated

DNA sequencing is the determination of the exact order of nucleotide bases in a region of DNA, producing an ordered string of As, Ts, Cs and Gs. [1 — sequencing defined] DNA profiling, by contrast, compares patterns at selected DNA marker regions between samples and produces a band or peak pattern rather than the base order itself. [1 — profiling defined] The two outputs are not interchangeable: sequencing returns the molecule's actual sequence so a specific inherited variant can be named, while profiling returns a similarity pattern at chosen loci and so identifies relatedness rather than cause. [1 — contrasts outputs]

For investigating inheritance patterns in a population, the choice depends on the question. If the program wants to know how often a known disease-linked SNP appears in the population — for example, identifying which families carry the CFTR ΔF508 variant — sequencing is required because the actual base change must be read at that position. [1 — variant identification + 1 — sequencing example] If the question is instead about relatedness — for example, whether several individuals in a community share a recent common ancestor — profiling at multiple STR marker loci is more efficient and is the standard approach. [1 — second criterion: relatedness/profiling example]

Neither technology is universally superior. They answer complementary questions about inheritance patterns: sequencing reveals the precise molecular basis of inherited variation, while profiling efficiently compares samples at selected markers. The most informative population-inheritance programs use both, matched to the specific inference being made. [1 — purpose-dependent judgement]

Marking criteria (7 marks):

• 1 mark — Defines DNA sequencing as the determination of nucleotide base order in DNA.
• 1 mark — Defines DNA profiling as the comparison of patterns at selected DNA marker regions between samples.
• 1 mark — Contrasts the outputs: ordered base string vs marker-pattern profile, with one consequence.
• 1 mark — Compares the two on variant identification: sequencing identifies specific SNPs/mutations directly; profiling indicates similarity but not the underlying base change.
• 1 mark — Compares on a second criterion (e.g. relatedness inference, throughput/cost, novel-variant detection).
• 1 mark — Uses a named example for each technology (sequencing — e.g. CFTR ΔF508 screening; profiling — e.g. STR-marker relatedness comparison).
• 1 mark — Reaches a purpose-dependent judgement linked to investigating inheritance patterns in populations.

Q2 — Sample Band 6 response (8 marks), annotated

Reading the bands directly: M carries one top-position allele and one middle-position allele; F carries one middle-position allele and one bottom-position allele. C1 (affected) has one top allele (from M) and one bottom allele (from F); C2 (unaffected) has one middle allele from M and one middle allele from F. [1 — reads profile correctly] The affected child has inherited the "top + bottom" combination, while the unaffected child has not, which is consistent with the disease being associated with one of these two alleles at this marker in this family. [1 — affected vs unaffected combination]

However, the profile shows an association only. The marker may not itself be the gene that causes the disease — it could simply be physically near the causal gene and co-inherited with it (linkage). [1 — marker association vs cause] Critically, the bands do not show the actual base change responsible: profiling shows fragment-size pattern, not nucleotide order. Without sequencing, the team cannot name the underlying mutation. [1 — no base-order from profile]

Adding sequencing would substantially improve the inference. First, it would reveal the actual variant — for example a specific SNP or small deletion — allowing a direct molecular diagnosis. [1 — criterion 1] Second, the identified variant could be compared with public population databases to estimate its frequency and whether the same variant has been seen in other affected families, supporting inheritance-pattern claims at the population level. [1 — criterion 2] Third, sequencing the whole region would reveal any additional variants in nearby genes that could be modifying severity or risk, which a single profiling marker cannot detect. [1 — criterion 3]

Recommendation: the clinical team should commission sequencing. Profiling at one marker has identified an inheritance pattern worth investigating, but only sequencing can characterise the actual molecular cause and place this family within the wider population-inheritance picture. [1 — justified recommendation tied to inheritance inference]

Marking criteria (8 marks):

• 1 mark — Reads the profile correctly: identifies which parental allele each child has inherited at this marker.
• 1 mark — Identifies that the affected and unaffected children carry different allele combinations at this marker, consistent with disease association in this family.
• 1 mark — Recognises the profile shows an association at this marker, not the actual causal mutation (marker may be near, not within, the causal gene).
• 1 mark — Identifies that profiling does not provide the base order, so the underlying disease-linked variant cannot be named from these bands.
• 1 mark — Evaluates sequencing on criterion 1 (reveals the actual base change for direct molecular diagnosis).
• 1 mark — Evaluates sequencing on criterion 2 (allows comparison with population databases to estimate frequency / inheritance pattern).
• 1 mark — Evaluates sequencing on criterion 3 (detects additional variants in the region not predictable from family inheritance).
• 1 mark — Reaches a justified recommendation linking the choice to inheritance-pattern inference for this family.

Q3 — Sample Band 6 response (6 marks)

The claim is largely incorrect. It conflates DNA profiling with whole-genome sequencing and overstates what either technology can do. [1 — overall judgement]

Central error. DNA profiling does not read every base in the whole genome. Profiling compares patterns at selected marker regions only; the actual base order at most positions is never read. The base-order claim describes sequencing, not profiling. [1 — central error identified]

• "Predicts every disease you will ever develop." Even full whole-genome sequencing identifies risk-associated variants probabilistically. Most diseases have a multifactorial basis (multiple genes plus environment) and cannot be deterministically predicted from DNA alone. [1 — refutes universal prediction]
• "Every relative you have ever had." Relatedness inference from any DNA technology is statistical, depends on the marker set used, and requires reference samples. It can identify likely close relatives within a database, not "every relative ever". [1 — refutes universal relatedness claim]
• "No scientific reason to use sequencing separately." Sequencing is the technology that produces base-order data — it is required for identifying specific inherited variants, characterising novel mutations, and comparing populations at the nucleotide level. Profiling cannot substitute for these tasks. [1 — refutes redundancy claim]

Defensible reformulation: "DNA sequencing and DNA profiling are related but distinct technologies. Sequencing determines the actual order of nucleotide bases in a DNA region, allowing specific inherited variants to be identified directly. Profiling compares patterns at selected DNA marker regions and is used to compare or relate samples — for example, supporting inferences about relatedness. Both technologies inform our understanding of inheritance patterns in populations, but they answer different questions and neither makes the other redundant." [1 — defensible reformulation]

Marking criteria (6 marks):

• 1 mark — States an overall evaluative judgement (claim largely incorrect / conflates sequencing and profiling).
• 1 mark — Identifies the central error: profiling does not read every base in the whole genome — it compares patterns at selected marker regions.
• 1 mark — Refutes "predicts every disease you will ever develop" — even full sequencing identifies risk variants probabilistically; multifactorial disease outcomes depend on multiple genes plus environment.
• 1 mark — Refutes "every relative you have ever had" — relatedness inference is statistical, marker-bounded, and requires reference samples.
• 1 mark — Refutes "no scientific reason to use sequencing separately" — sequencing is required for base-order data and specific-variant identification.
• 1 mark — Reformulates the claim into a defensible statement that distinguishes sequencing from profiling and links each to its inheritance-pattern question.