Pharmacogenomics: gene mapping and disease gene cloning MCQs With Answer

Pharmacogenomics: gene mapping and disease gene cloning MCQs With Answer is designed for M.Pharm students to bridge molecular genetics and personalized therapeutics. This collection focuses on genetic mapping approaches, positional cloning strategies, molecular markers, and modern association methods that identify loci affecting drug response and disease susceptibility. Questions emphasize analytical concepts such as linkage analysis, LOD scores, recombination, homozygosity mapping, SNPs, GWAS, and physical mapping techniques, as well as practical cloning workflows and interpretative challenges. The aim is to strengthen conceptual understanding and problem-solving skills needed for research, clinical pharmacogenomics, and advanced coursework in cellular and molecular pharmacology.

Q1. What is the primary objective of gene mapping in pharmacogenomics?

• To determine dosing regimens for existing drugs based solely on weight
• To identify genomic loci associated with drug response and adverse effects
• To sequence the entire transcriptome of a cell under drug treatment
• To create transgenic animals for drug testing

Correct Answer: To identify genomic loci associated with drug response and adverse effects

Q2. Which feature best distinguishes linkage analysis from population-based association studies?

• Linkage analysis uses unrelated individuals to detect common variants
• Linkage analysis examines co-segregation of markers with disease in families
• Linkage analysis requires whole-genome sequencing of all subjects
• Linkage analysis is optimized to detect very small effect common variants

Correct Answer: Linkage analysis examines co-segregation of markers with disease in families

Q3. In human genetics, what LOD (logarithm of odds) score is commonly accepted as evidence for significant linkage?

• LOD ≥ 1.0
• LOD ≥ 2.0
• LOD ≥ 3.0
• LOD ≥ 4.5

Correct Answer: LOD ≥ 3.0

Q4. The recombination fraction (theta) between two loci represents:

• The number of base pairs between the loci on the chromosome
• The proportion of meioses in which a recombination event occurs between the loci
• The mutation rate per generation at the loci
• The probability of both loci being expressed in the same tissue

Correct Answer: The proportion of meioses in which a recombination event occurs between the loci

Q5. What is typically the first experimental step in positional cloning of a disease gene?

• Performing high-throughput drug screens on patient cells
• Mapping the disease locus using linkage analysis in families
• Conducting proteomic profiling of diseased tissue
• Knocking out candidate genes in animal models

Correct Answer: Mapping the disease locus using linkage analysis in families

Q6. Which class of molecular marker became the standard for high-resolution genome-wide association studies (GWAS)?

• Restriction fragment length polymorphisms (RFLPs)
• Short tandem repeats (STRs)
• Single nucleotide polymorphisms (SNPs)
• Variable number tandem repeats (VNTRs)

Correct Answer: Single nucleotide polymorphisms (SNPs)

Q7. Homozygosity mapping is most powerful for identifying disease loci in which scenario?

• Late-onset dominant disorders in outbred populations
• Recessive disorders in consanguineous families
• Complex traits influenced by many common variants
• Somatic mutations in cancer tissues

Correct Answer: Recessive disorders in consanguineous families

Q8. Which physical mapping technique is commonly used to order overlapping genomic clones during map-based cloning?

• Chromosome walking using overlapping clones
• RNA interference knockdown mapping
• CRISPR-Cas9 target mapping
• Mass spectrometry peptide mapping

Correct Answer: Chromosome walking using overlapping clones

Q9. The founder effect in a population most directly results in which genetic observation?

• Rapid increase in recombination rate across the genome
• High prevalence of a specific pathogenic allele due to descent from a common ancestor
• Complete elimination of deleterious alleles from the population
• Uniform heterozygosity across all loci

Correct Answer: High prevalence of a specific pathogenic allele due to descent from a common ancestor

Q10. The candidate gene approach to finding genotype-phenotype associations primarily depends on:

• Genome-wide unbiased scanning of millions of markers
• Prior biological knowledge about a gene’s function and pathway
• Random selection of genes for sequencing
• Only family-based linkage without any functional rationale

Correct Answer: Prior biological knowledge about a gene’s function and pathway

Q11. A major limitation of GWAS in pharmacogenomics is that it:

• Only identifies rare variants with large effect sizes
• Requires very small sample sizes to detect associations
• Primarily detects common variants of small effect and needs large cohorts
• Directly proves causality for identified loci without further study

Correct Answer: Primarily detects common variants of small effect and needs large cohorts

Q12. Positional cloning is characterized by which defining principle?

• Discovery of genes based exclusively on known protein function
• Identification of disease genes by mapping location without prior functional knowledge
• Immediate generation of animal models before gene identification
• Reliance solely on expression differences between tissues

Correct Answer: Identification of disease genes by mapping location without prior functional knowledge

Q13. What does a LOD score of -2 indicate in linkage analysis?

• Strong evidence for linkage
• Ambiguous evidence, requiring more data
• Evidence against linkage, allowing exclusion of linkage
• Proof that the trait is polygenic

Correct Answer: Evidence against linkage, allowing exclusion of linkage

Q14. Which method is routinely used to detect copy number variations (CNVs) across the genome?

• Comparative genomic hybridization (CGH) arrays
• Western blotting
• Methylation-specific PCR for promoter regions
• Sanger sequencing of exons only

Correct Answer: Comparative genomic hybridization (CGH) arrays

Q15. A haplotype is best described as:

• A single nucleotide polymorphism at one locus
• A combination of alleles or SNPs at adjacent loci transmitted together
• A type of copy number variant
• An RNA splice variant

Correct Answer: A combination of alleles or SNPs at adjacent loci transmitted together

Q16. Allelic heterogeneity refers to which genetic phenomenon?

• Different mutations in the same gene producing similar clinical phenotypes
• Mutations in different genes causing the same disorder
• Multiple genes combining to produce a single phenotype
• Environmental factors modifying gene expression

Correct Answer: Different mutations in the same gene producing similar clinical phenotypes

Q17. Locus heterogeneity implies that:

• A single mutation causes multiple unrelated diseases
• Mutations in different genes can lead to a similar clinical phenotype
• Only one locus controls a complex trait
• All affected individuals share an identical mutation

Correct Answer: Mutations in different genes can lead to a similar clinical phenotype

Q18. Which of the following is NOT a standard step in classical map-based (positional) cloning?

• Refining the linkage region by genotyping additional markers
• Generating a physical contig and identifying candidate genes
• Performing in vitro drug assays unrelated to gene identification
• Sequencing candidate genes and testing for pathogenic variants

Correct Answer: Performing in vitro drug assays unrelated to gene identification

Q19. Expression cloning is a technique that identifies genes based on:

• Their chromosomal position determined by linkage only
• Functional activity of expressed cDNA in a heterologous assay or pattern of expression
• Whole-genome association p-values exclusively
• Protein tertiary structure predictions alone

Correct Answer: Functional activity of expressed cDNA in a heterologous assay or pattern of expression

Q20. A key ethical concern specific to pharmacogenomic gene mapping and cloning is:

• The inability to sequence DNA accurately
• Guaranteed therapeutic benefit for all participants
• Potential for genetic discrimination and privacy breaches
• Lack of any need for informed consent

Correct Answer: Potential for genetic discrimination and privacy breaches

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