STP Genomics & Molecular Biology 2 — Questions and Answers
Question 1: A genome-wide association study (GWAS) is designed primarily to:
- Sequence every coding exon in an individual's genome
- Identify statistical associations between common genetic variants and specific traits or diseases (Correct answer)
- Detect de novo mutations arising in a single generation
- Determine the three-dimensional structure of the genome
Correct answer: Identify statistical associations between common genetic variants and specific traits or diseases
GWAS scans the genomes of large populations to identify SNPs or other variants that are statistically associated with a phenotype or disease, without a prior hypothesis about specific genes.
Question 2: Copy number variations (CNVs) refer to:
- Point mutations that alter a single amino acid in a protein
- Segments of DNA ≥1 kb present in a variable number of copies relative to a reference genome (Correct answer)
- Epigenetic modifications that alter gene expression without changing the DNA sequence
- Chromosomal translocations between non-homologous chromosomes
Correct answer: Segments of DNA ≥1 kb present in a variable number of copies relative to a reference genome
CNVs are structural variants typically ≥1 kb in size where the number of copies of a genomic segment differs between individuals, contributing to phenotypic diversity and disease susceptibility.
Question 3: RNA sequencing (RNA-seq) is used in clinical and research genomics to:
- Amplify specific RNA targets using reverse-transcribed cDNA only
- Quantify and characterise the transcriptome, including expression levels and splicing variants (Correct answer)
- Edit specific RNA sequences using base-editing enzymes
- Detect chromosomal aneuploidies from cell-free RNA in plasma
Correct answer: Quantify and characterise the transcriptome, including expression levels and splicing variants
RNA-seq converts the transcriptome to cDNA and sequences it using NGS, providing quantitative gene expression data and revealing transcript isoforms and fusion genes.
Question 4: CRISPR-Cas9 gene editing works by:
- Using restriction enzymes to make blunt-end cuts at random genomic locations
- Guided RNA directing the Cas9 endonuclease to a specific genomic sequence where it introduces a double-strand break (Correct answer)
- Inserting foreign DNA via retroviral integration at semi-random sites
- Methylating specific promoter regions to silence targeted genes
Correct answer: Guided RNA directing the Cas9 endonuclease to a specific genomic sequence where it introduces a double-strand break
A single guide RNA (sgRNA) complementary to the target sequence directs Cas9 to that locus where it creates a site-specific double-strand break, triggering repair pathways that can be exploited for editing.
Question 5: In genomic medicine, a 'variant of uncertain significance' (VUS) means that:
- The variant is confirmed to cause the patient's disease
- The variant is benign and can be dismissed from clinical consideration
- Insufficient evidence exists to classify the variant as pathogenic or benign (Correct answer)
- The variant has been found only in population databases, never in patients
Correct answer: Insufficient evidence exists to classify the variant as pathogenic or benign
VUS designates variants where current evidence is insufficient to determine pathogenicity, requiring follow-up studies, familial segregation analysis, or functional data before clinical action is taken.
Question 6: Pharmacogenomics is primarily concerned with:
- Developing new drugs using recombinant DNA technology
- How genetic variation influences an individual's response to drugs, including efficacy and adverse reactions (Correct answer)
- Measuring drug concentrations in plasma using mass spectrometry
- Screening drug candidates for mutagenic potential
Correct answer: How genetic variation influences an individual's response to drugs, including efficacy and adverse reactions
Pharmacogenomics examines how inherited genetic differences in drug-metabolising enzymes, transporters, and targets affect drug response, enabling personalised medicine approaches.
Question 7: Whole exome sequencing (WES) targets approximately what proportion of the human genome?
- ~50% of the genome, including all repetitive elements
- ~1–2% of the genome, encompassing protein-coding exons (Correct answer)
- ~10% of the genome, including all regulatory regions
- ~0.01% of the genome, covering only known pathogenic variants
Correct answer: ~1–2% of the genome, encompassing protein-coding exons
The exome constitutes roughly 1–2% of the genome (~30 Mb) but contains the majority of currently known disease-causing variants, making WES an efficient diagnostic strategy.
STP Genomics & Molecular Biology 2
A genome-wide association study (GWAS) is designed primarily to: