Genetics and Personalised Medicine

• A. 23
• B. 46 ✓
• C. 64
• D. 92

Why: Human somatic cells are diploid, containing 23 pairs of chromosomes, which totals 46 chromosomes. Gametes (sperm and egg) carry only 23 chromosomes each.

• A. Chromosome
• B. Nucleotide
• C. Gene ✓
• D. Protein

Why: A gene is a segment of DNA that encodes the instructions for a particular trait or for making a functional product such as a protein. Chromosomes are structures that carry many genes, while nucleotides are the building blocks of DNA.

• A. A single strand of nucleotides folded into a loop
• B. Two strands forming a double helix held together by base pairing ✓
• C. Three strands wound around a central protein core
• D. A chain of amino acids joined by peptide bonds

Why: DNA consists of two complementary strands forming a double helix. The strands are held together by hydrogen bonds between base pairs: adenine pairs with thymine, and guanine pairs with cytosine.

• A. Phenotype
• B. Genome ✓
• C. Proteome
• D. Allele

Why: The genome is the complete set of genetic material in an organism. The phenotype refers to observable traits, the proteome is the full set of proteins, and an allele is one of several variant forms of a gene.

• A. Heterozygous
• B. Hemizygous
• C. Homozygous recessive ✓
• D. Homozygous dominant

Why: Homozygous recessive means both copies of the gene are the same recessive allele, so the recessive trait is expressed. Heterozygous means two different alleles are present, and homozygous dominant means two copies of the dominant allele.

• A. The three-dimensional shape of a protein
• B. The exact order of nucleotide bases in a DNA molecule ✓
• C. The number of chromosomes in a cell
• D. The rate at which cells divide

Why: DNA sequencing identifies the order of the four nucleotide bases (A, T, C, G) along a DNA strand, which encodes genetic information.

• A. Adenine, guanine, uracil, cytosine
• B. Adenine, thymine, guanine, cytosine ✓
• C. Adenine, thymine, uracil, glycine
• D. Guanine, cytosine, serine, thymine

Why: DNA is composed of adenine (A), thymine (T), guanine (G), and cytosine (C). Uracil replaces thymine in RNA, not DNA.

• A. Measuring light emitted by single molecules in real time
• B. Using chain-terminating dideoxynucleotides to produce DNA fragments of different lengths ✓
• C. Detecting pH changes caused by hydrogen ions released during nucleotide incorporation
• D. Separating DNA strands by their electrical charge alone

Why: Sanger sequencing incorporates dideoxynucleotides (ddNTPs) that halt DNA synthesis at specific bases. The resulting fragments of varying lengths are separated to read the sequence.

• A. Sequencing only a single gene at a time with higher accuracy
• B. Sequencing millions of DNA fragments in parallel, producing far more data at lower cost per base ✓
• C. Sequencing only RNA molecules rather than DNA
• D. Eliminating the need for any sample preparation

Why: NGS platforms sequence massively parallel reactions, enabling whole genomes or large gene panels to be sequenced quickly and at much lower cost per base than Sanger methods.

• A. It replaces the need for all clinical diagnosis
• B. It identifies genetic variants that can guide choice of treatment and assess disease risk for an individual ✓
• C. It determines a person's blood type only
• D. It converts DNA into proteins for therapy

Why: By revealing an individual's genetic variants, sequencing helps clinicians predict drug responses, identify hereditary risks, and tailor treatments to each patient.

• A. A large deletion of several genes on a chromosome
• B. A variation in a single DNA base position that occurs in a meaningful proportion of the population ✓
• C. A rearrangement of entire chromosome segments
• D. A protein that binds to a specific DNA sequence

Why: A SNP is a variation at a single base pair position in the genome that is common enough to be found in at least about 1% of the population. Large deletions and chromosomal rearrangements are structural variants, not SNPs.

• A. Silent mutation
• B. Nonsense mutation
• C. Missense mutation ✓
• D. Frameshift mutation

Why: A missense mutation alters a single base so that the codon specifies a different amino acid. Silent mutations keep the same amino acid, nonsense mutations create a stop codon, and frameshifts shift the reading frame.

• A. Insulin
• B. Haemoglobin beta chain ✓
• C. Collagen
• D. Dystrophin

Why: Sickle cell anaemia results from a single base change in the HBB gene, which encodes the beta-globin chain of haemoglobin. This substitution replaces glutamic acid with valine, causing haemoglobin to polymerise under low oxygen.

• A. The recessive allele is deleted in all body cells
• B. The second, normal allele produces enough functional protein to maintain normal function ✓
• C. The recessive allele only functions in adulthood
• D. The allele is silenced by methylation in every cell

Why: Carriers have one functional copy of the gene, which is typically sufficient to produce enough working protein. Disease appears in recessive conditions only when both copies are non-functional.

• A. Mutation
• B. Polymorphism ✓
• C. Pathogenic variant
• D. Deletion syndrome

Why: A polymorphism is a variant that is present in a population at a frequency generally above 1%. Pathogenic variants cause disease, and mutation is a broader term that does not imply prevalence.

• A. The study of how drugs are manufactured on an industrial scale
• B. The study of how an individual's genetic makeup affects their response to drugs ✓
• C. The study of how environmental toxins alter DNA sequences
• D. The study of bacterial resistance to antibiotics

Why: Pharmacogenomics examines how genetic variation influences drug efficacy and toxicity, enabling more personalised prescribing.

• A. Cytochrome P450 (CYP) ✓
• B. Hemoglobin
• C. Lactate dehydrogenase
• D. Collagenase

Why: The cytochrome P450 enzyme family, especially CYP2D6, CYP2C19 and CYP2C9, metabolises a large proportion of clinically used drugs, so variants in these genes strongly affect drug levels.

• A. Rapid conversion to morphine causing toxicity
• B. Reduced conversion to morphine, leading to little pain relief ✓
• C. Complete absorption failure in the gut
• D. Increased excretion by the kidneys with no clinical effect

Why: Codeine is a prodrug activated by CYP2D6 into morphine. Poor metabolisers produce little active morphine, so analgesia is reduced, whereas ultra-rapid metabolisers risk morphine toxicity.

• A. The individual has no functional copies of the drug-metabolising gene
• B. The individual metabolises a drug much faster than average, often due to gene duplication ✓
• C. The individual cannot absorb the drug through the intestine
• D. The individual has an allergy to the drug's active ingredient

Why: Ultra-rapid metabolisers often carry extra functional copies of a gene such as CYP2D6, clearing drugs quickly so standard doses may be ineffective.

• A. Clopidogrel is only effective in patients with a specific blood type
• B. Clopidogrel is a prodrug activated by CYP2C19, and carriers of loss-of-function variants have reduced antiplatelet effect ✓
• C. Clopidogrel must be matched to the patient's HLA type to avoid rash
• D. Clopidogrel is excreted unchanged so kidney function must be tested

Why: Clopidogrel requires activation by CYP2C19. Patients with loss-of-function alleles get less protection against clotting events, so genotyping can guide alternative therapy.

• A. The aligned positions of reads on a reference genome
• B. Raw sequencing reads along with their per-base quality scores ✓
• C. Annotated variant calls with clinical significance
• D. Gene expression counts for each transcript

Why: FASTQ files contain the raw nucleotide sequences produced by a sequencer, with a quality score for each base. Alignment and variant calling happen in later steps.

• A. To determine where each read most likely originated in the genome ✓
• B. To compress the file size of the sequencing data
• C. To remove low-quality bases from the reads
• D. To translate DNA sequences into protein sequences

Why: Alignment (mapping) places each read at its most likely genomic location, which is the foundation for detecting variants and measuring coverage.

• A. A large deletion spanning many thousands of bases
• B. A single base position that differs between individuals in a population ✓
• C. A copy number gain of an entire chromosome
• D. A type of RNA molecule involved in splicing

Why: A single nucleotide polymorphism (SNP) is a variation at one base position that occurs in a meaningful fraction of the population.

• A. The percentage of the genome that contains genes
• B. The average number of reads covering a given genomic position ✓
• C. The length of the longest read in the dataset
• D. The number of samples sequenced in one run

Why: Coverage describes how many reads overlap a typical base. Higher coverage gives more confidence when calling variants.

• A. It stores raw fluorescence images from the sequencer
• B. It standardly records genetic variants and their genotypes across samples ✓
• C. It stores protein structures predicted from DNA
• D. It holds the phenotype records of patients

Why: The Variant Call Format (VCF) is a standard text format for describing variants, their positions, and sample genotypes, making it central to downstream analysis.

• A. Beneficence
• B. Informed consent ✓
• C. Justice
• D. Non-maleficence

Why: Informed consent requires that patients receive clear, understandable information about a genetic test, including its purpose, risks, benefits, and limitations, before voluntarily agreeing to it.

• A. The right to choose which genetic tests are performed on a family member
• B. Protecting an individual's genetic information from unauthorised access, use, or disclosure ✓
• C. The requirement that all genetic data be stored in a public database
• D. The ability of researchers to freely share patient DNA samples

Why: Genetic privacy concerns safeguarding a person's genetic information so it is not accessed, used, or shared without their permission, since genetic data can reveal sensitive information about health and relatives.

• A. Offering different treatments based on a patient's ethnicity
• B. Treating individuals unfavourably in employment or insurance because of their genetic information ✓
• C. Refusing to perform a genetic test because it is expensive
• D. Limiting access to research studies based on age

Why: Genetic discrimination occurs when people are treated unfairly, such as being denied employment or insurance coverage, because of genetic predispositions or test results.

• A. To guarantee that the test result will be positive
• B. To help individuals understand results, their implications, and available choices ✓
• C. To determine the price the patient will pay for the test
• D. To replace the need for a physician's diagnosis

Why: Genetic counselling supports patients in understanding the meaning of test results, the implications for themselves and their families, and the options available to them, both emotionally and medically.

• A. The right to refuse treatment
• B. The duty of confidentiality, and the question of whether relatives should be informed ✓
• C. The obligation to publish research findings
• D. The cost of testing for multiple family members

Why: Genetic results can affect blood relatives who share the same variants, creating tension between a patient's confidentiality and relatives' interest in knowing information that may be relevant to their own health.

• A. To develop one standard treatment that works for all patients with a given disease
• B. To tailor medical decisions and treatments to an individual's genetic, environmental, and lifestyle characteristics ✓
• C. To reduce the cost of hospital care by limiting diagnostic testing
• D. To replace physicians with automated diagnostic software

Why: Personalised medicine uses information about an individual's genes, environment, and lifestyle to guide prevention, diagnosis, and treatment, rather than applying a one-size-fits-all approach.

• A. Using genetic testing to check for TPMT variants before prescribing thiopurine drugs such as azathioprine ✓
• B. Using blood pressure readings to diagnose hypertension
• C. Using X-rays to diagnose bone fractures
• D. Using body mass index to estimate body fat percentage

Why: TPMT genotyping helps identify patients at risk of severe myelosuppression from thiopurines, allowing dose adjustment. This is a classic pharmacogenomic application.

• A. A diagnostic test used to identify patients who are likely to benefit from a specific targeted therapy ✓
• B. A second opinion provided by a family doctor
• C. A diagnostic tool that monitors a patient's mental wellbeing at home
• D. A generic blood test ordered for all hospital admissions

Why: Companion diagnostics are tests, often genetic or biomarker-based, that are developed alongside a drug to determine which patients should receive it, such as HER2 testing before trastuzumab in breast cancer.

• A. HER2 status determines whether a patient will respond to trastuzumab, a targeted therapy ✓
• B. HER2 testing measures the patient's cholesterol level
• C. HER2 is a bacterium that causes breast infections
• D. HER2 testing is only used to determine the patient's age

Why: Tumours overexpressing or amplifying HER2 respond well to HER2-targeted drugs such as trastuzumab, so testing guides treatment selection.

• A. It guarantees that a person will develop a disease if a risk variant is found
• B. It estimates the likelihood of developing a condition and can guide screening and preventive measures ✓
• C. It is only useful for diseases with no known treatment
• D. It replaces the need for family history taking

Why: Genetic risk assessment estimates probability rather than certainty. Results can inform surveillance, screening intensity, and preventive strategies, such as BRCA1/2 testing guiding enhanced breast cancer surveillance.