Genomics

Q1. (6 marks) — 2 marks each

• (a) Genome — the complete set of genetic material (DNA) of an organism, including all genes and non-coding sequences. (1 for "complete DNA/genetic material", 1 for "all genes + non-coding")
• (b) Proteome — the complete set of proteins expressed by a genome/cell/organism at a given time. (1 for "set of proteins", 1 for "expressed by genome / time-specific")
• (c) Transcriptome — the complete set of RNA transcripts (especially mRNA) produced by a genome under specific conditions. (1 for "set of RNA transcripts", 1 for "produced/expressed under conditions")

Q2. (3 marks)

• Any two aims (1 mark each): to determine the complete DNA sequence of the human genome; to identify and map all human genes; to store data in databases; to develop tools for analysis; address ethical issues (ELSI).
• Number of protein-coding genes ≈ 20,000–25,000 (1 mark). Why: HGP surprisingly found far fewer genes than expected.

Q3. (5 marks)

• Uses DNA polymerase to synthesise new strands from a template primer (1).
• Reaction mixture contains normal dNTPs plus a small proportion of dideoxynucleotides (ddNTPs) (1).
• ddNTPs lack the 3'-OH group, so when incorporated they terminate chain elongation (1) — the "why": no 3'-OH means no phosphodiester bond can form.
• This produces DNA fragments of varying lengths, each ending in a specific ddNTP (1).
• Fragments are separated by size (gel/capillary electrophoresis) and the sequence read from the ordered fragments; ddNTPs are fluorescently labelled by base (1).

Q4. (3 marks) — any three, 1 mark each

• NGS is massively parallel (millions of reads simultaneously) vs Sanger sequences one fragment at a time.
• NGS is faster and higher throughput.
• NGS is cheaper per base.
• Sanger gives longer, more accurate individual read lengths.
• NGS requires bioinformatic assembly of short reads.

Q5. (5 marks)

• Whole-genome sequencing (WGS): sequencing the entire genome — both coding and non-coding DNA (1).
• Exome sequencing: sequencing only the protein-coding regions (exons) of the genome (1).
• Key distinction: WGS covers ~100% of genome; exome covers ~1–2% but captures most disease-causing mutations (1).
• Calculation: $0.015 \times 3.2\times10^9 = 4.8\times10^7$ (1).
• Exome ≈ 48 million base pairs (48 Mb) (1).

Q6. (4 marks)

• (a) Genome annotation — the process of identifying the locations and functions of genes and other features within a genome sequence (2).
• (b) Any two (1 each): protein-coding genes/ORFs; exon–intron boundaries; regulatory sequences (promoters, enhancers); non-coding RNA genes; repetitive elements.

Q7. (5 marks)

• (a) A SNP is a variation in a single nucleotide base at a specific position in the genome that occurs in a population (2). (1 for "single base change", 1 for "at defined position / in population")
• (b) In GWAS, the genomes of many individuals with and without a trait/disease are scanned for SNPs (1); SNPs occurring more frequently in affected individuals are identified (1); these are statistically associated with the trait, pointing to genomic regions linked to disease risk (1).

Q8. (3 marks)

• Comparative genomics — the study that compares the genome sequences of different species (or organisms) to identify similarities and differences (2).
• One application (1): identifying conserved (functional) regions; studying evolutionary relationships; finding disease-related genes using model organisms.

Q9. (3 marks)

• ENCODE (Encyclopedia of DNA Elements) found that a large proportion of non-coding DNA is functional/biochemically active (1) — despite not coding for proteins (1).
• Much non-coding DNA acts as regulatory elements (promoters, enhancers) or is transcribed into functional non-coding RNAs, challenging the idea of "junk DNA" (1).

Q10. (4 marks)

• (a) Pharmacogenomics — the study of how an individual's genome/genetic makeup affects their response to drugs (2).
• (b) It allows selection of drugs and doses tailored to a patient's genotype (1), improving efficacy and reducing adverse reactions — a key part of personalized/precision medicine (1).

[
  {"claim": "Exome size = 1.5% of 3.2 billion bp = 48 million bp", "code": "exome = Rational(15,1000)*3.2e9; result = abs(exome - 48e6) < 1"},
  {"claim": "Exome as fraction gives 4.8e7", "code": "val = 0.015*3.2*10**9; result = abs(val - 4.8*10**7) < 1"},
  {"claim": "Human protein-coding gene count midpoint ~22500 lies in 20000-25000 range", "code": "lo,hi=20000,25000; mid=(lo+hi)/2; result = lo <= mid <= hi"}
]