Molecular Biology and Genomics — MCQs

Molecular Biology and Genomics Indian Medical PG Practice Questions and MCQs

Question 491: Which of the following techniques can be used to differentiate the chromosomal abnormalities between normal and cancer cells?

A. Polymerase Chain Reaction (PCR)
B. Comparative Genomic Hybridization (CGH) (Correct Answer)
C. Karyotyping
D. Western Blotting

Explanation: **Explanation:** The correct answer is **Comparative Genomic Hybridization (CGH)**. **1. Why CGH is the correct answer:** CGH is a molecular cytogenetic technique used to detect **copy number variations (CNVs)**—specifically gains (amplifications) or losses (deletions) of whole chromosomes or specific chromosomal regions. In this method, DNA from a "test" sample (cancer cell) and a "reference" sample (normal cell) are labeled with different fluorescent dyes (usually green and red) and hybridized to a normal metaphase spread or a microarray. By comparing the fluorescence ratio, clinicians can identify unbalanced chromosomal abnormalities characteristic of malignancies, such as oncogene amplification or tumor suppressor gene deletion. **2. Why other options are incorrect:** * **PCR:** Primarily used to amplify specific DNA sequences. While it can detect point mutations or small indels, it is not the standard tool for global chromosomal differentiation between cell types. * **Karyotyping:** While it visualizes chromosomes, it has low resolution (5–10 Mb) and requires living, dividing cells in metaphase. CGH provides much higher resolution and can be performed on archived or non-dividing tissue. * **Western Blotting:** This technique detects and quantifies specific **proteins**, not chromosomal or genomic DNA abnormalities. **Clinical Pearls for NEET-PG:** * **Array-CGH (aCGH):** The modern version using microarrays; it is the first-line investigation for children with developmental delays and multiple congenital anomalies. * **Limitation of CGH:** It cannot detect **balanced** chromosomal abnormalities like reciprocal translocations, inversions, or polyploidy, as there is no net change in the amount of DNA. * **FISH vs. CGH:** FISH requires a specific suspected probe; CGH scans the entire genome without prior knowledge of the specific abnormality.

Question 492: True about RNA Polymerase is:

A. Requires primers
B. RNA dependent DNA Polymerase
C. No proofreading activity (Correct Answer)
D. Recognizes Shine-Dalgarno sequence

Explanation: **Explanation:** The correct answer is **C. No proofreading activity.** Unlike DNA Polymerase, **RNA Polymerase (RNAP)** lacks the 3'→5' exonuclease activity required for proofreading. While RNAP has a very limited ability to pause and remove mismatched bases, it is significantly less efficient than DNA Polymerase. This results in a much higher error rate (approx. 1 in $10^4$ to $10^5$ nucleotides), which is evolutionarily tolerable because RNA is transient and not the permanent repository of genetic information. **Analysis of Incorrect Options:** * **A. Requires primers:** RNA Polymerase is capable of **de novo** synthesis. It can initiate the formation of a phosphodiester bond between two free nucleotides without a pre-existing 3'-OH primer, unlike DNA Polymerase. * **B. RNA dependent DNA Polymerase:** This describes **Reverse Transcriptase** (found in retroviruses like HIV). RNA Polymerase is a **DNA-dependent RNA polymerase**, as it uses a DNA template to synthesize RNA. * **D. Recognizes Shine-Dalgarno sequence:** The Shine-Dalgarno sequence is recognized by the **16S rRNA of the 30S ribosomal subunit** during the initiation of translation (protein synthesis), not by RNA polymerase during transcription. **High-Yield Clinical Pearls for NEET-PG:** * **Rifampicin:** Inhibits bacterial RNA Polymerase by binding to the $\beta$-subunit; used in Tuberculosis. * **$\alpha$-Amanitin:** Found in *Amanita phalloides* (death cap mushroom); it specifically inhibits **RNA Polymerase II**, leading to severe hepatotoxicity. * **Sigma ($\sigma$) Factor:** A subunit of prokaryotic RNAP holoenzyme required for **initiation** and recognition of the promoter site (Pribnow box). * **Eukaryotic RNAP Types:** * I: rRNA (except 5S) * II: mRNA (most sensitive to $\alpha$-amanitin) * III: tRNA and 5S rRNA.

Question 493: A young boy presents with difficulty in rising from a sitting position, and is diagnosed with Duchenne's muscular dystrophy. Which statement is true regarding mutations in the promoter region of the dystrophin gene?

A. Initiation of transcription of the dystrophin gene would be affected. (Correct Answer)
B. Capping of the mRNA of the dystrophin gene would be affected.
C. Tailing of the mRNA of the dystrophin gene would be affected.
D. Premature termination of translation would occur.

Explanation: ### Explanation **1. Why Option A is Correct:** The **promoter** is a specific regulatory sequence of DNA located upstream (5') of a gene. Its primary function is to serve as the binding site for RNA polymerase II and general transcription factors (like the TATA box binding protein). Because the promoter is responsible for the assembly of the transcription initiation complex, any mutation in this region directly impairs the **initiation of transcription**. If the promoter is defective, the RNA polymerase cannot bind or orient itself correctly, leading to a failure in synthesizing the primary mRNA transcript. **2. Why the Other Options are Incorrect:** * **Option B (Capping):** Capping involves adding a 7-methylguanosine to the 5' end of the nascent mRNA. This is a post-transcriptional modification governed by capping enzymes, not the DNA promoter. * **Option C (Tailing):** Polyadenylation (tailing) occurs at the 3' end of the mRNA and is directed by the polyadenylation signal sequence (AAUAAA) at the end of the gene, not the promoter at the beginning. * **Option D (Premature Translation Termination):** This is typically caused by **nonsense mutations** (a point mutation creating a UAG, UAA, or UGA stop codon) within the coding exons, or frameshift mutations. The promoter regulates transcription (DNA to RNA), whereas termination is a process of translation (RNA to Protein). **3. High-Yield Clinical Pearls for NEET-PG:** * **DMD Genetics:** The dystrophin gene is the **largest known human gene**, making it highly susceptible to spontaneous mutations. * **Common Mutation in DMD:** While promoter mutations can occur, the most common cause of Duchenne Muscular Dystrophy is **large deletions** (65%) leading to a **frameshift mutation**. * **Becker MD:** Caused by **in-frame mutations**, resulting in a truncated but partially functional protein (milder phenotype). * **Promoter Sequences:** Remember the **TATA box** (Hogness box) in eukaryotes and the **Pribnow box** (TATAAT) in prokaryotes are key promoter elements.

Question 494: In which type of RNA is the anticodon found?

A. Transfer RNA (t-RNA) (Correct Answer)
B. Messenger RNA (m-RNA)
C. Ribosomal RNA (r-RNA)
D. None of the above

Explanation: ### Explanation **Correct Answer: A. Transfer RNA (t-RNA)** The **anticodon** is a specific sequence of three nucleotides located on the anticodon loop of **t-RNA**. Its primary function is to recognize and base-pair with a complementary sequence of three nucleotides, known as the **codon**, found on the m-RNA. This interaction ensures that the correct amino acid (carried at the 3' end of the t-RNA) is incorporated into the growing polypeptide chain during translation. **Why other options are incorrect:** * **B. Messenger RNA (m-RNA):** m-RNA contains the **codon**, not the anticodon. It serves as the template that carries genetic information from DNA to the ribosome. * **C. Ribosomal RNA (r-RNA):** r-RNA is a structural and catalytic component of ribosomes. It facilitates the alignment of m-RNA and t-RNA and catalyzes peptide bond formation (peptidyl transferase activity) but does not contain anticodons. --- ### High-Yield Facts for NEET-PG: * **Wobble Hypothesis:** Proposed by Francis Crick, it states that the base pairing between the 3rd base of the codon and the 1st base of the anticodon is less stringent, allowing one t-RNA to recognize multiple codons. * **t-RNA Structure:** * **Secondary structure:** Cloverleaf model. * **Tertiary structure:** L-shaped. * **Acceptor Arm:** The 3' end of t-RNA always ends in the sequence **CCA**, where the amino acid attaches to the terminal Adenosine. * **DHU Loop:** Contains dihydrouridine; responsible for recognition by the enzyme *aminoacyl t-RNA synthetase*. * **TψC Loop:** Contains pseudouridine; involved in binding the t-RNA to the ribosomal surface.

Question 495: Which enzymatic mutation is responsible for immortality of cancer cells?

A. DNA reverse transcriptase
B. RNA polymerase
C. Telomerase (Correct Answer)
D. DNA polymerase

Explanation: **Explanation:** The correct answer is **Telomerase**. **1. Why Telomerase is Correct:** Normal somatic cells have a finite lifespan (the **Hayflick limit**) because their linear chromosomes shorten with every cell division. This occurs because DNA polymerase cannot replicate the 3' ends of linear DNA (the "end-replication problem"). **Telomeres** are repetitive DNA sequences (TTAGGG) at chromosome ends that protect genomic integrity. In cancer cells, the enzyme **Telomerase** (a specialized ribonucleoprotein) is pathologically reactivated. Telomerase acts as a **reverse transcriptase**, using its own RNA template to add telomeric repeats to the 3' ends, thereby maintaining chromosome length indefinitely. This prevents senescence and apoptosis, granting cancer cells **replicative immortality**. **2. Why Other Options are Incorrect:** * **DNA reverse transcriptase (A):** While telomerase is a type of reverse transcriptase, this general term usually refers to viral enzymes (like in HIV) that convert viral RNA into DNA. It is not the specific driver of cellular immortality. * **RNA polymerase (B):** This enzyme is responsible for transcription (DNA to RNA). While upregulated in many cancers to support growth, it does not prevent the shortening of chromosomes. * **DNA polymerase (D):** This is the primary enzyme for DNA replication. Although essential for cell division, it cannot solve the end-replication problem on its own; without telomerase, DNA polymerase would still result in progressive telomere shortening. **3. High-Yield Clinical Pearls for NEET-PG:** * **Telomerase Components:** It consists of **TERT** (Telomerase Reverse Transcriptase - the catalytic subunit) and **TERC** (Telomerase RNA - the template). * **Cancer Association:** Telomerase activity is detected in **85-90%** of human cancers. * **Alternative Lengthening of Telomeres (ALT):** A small percentage of cancers maintain telomeres via homologous recombination rather than telomerase. * **Stem Cells:** Normal germ cells and embryonic stem cells naturally express high telomerase, unlike differentiated somatic cells.

Question 496: For karyotyping, the dividing cells are arrested by the addition of colchicines in which mitotic phase?

A. Telophase
B. Metaphase (Correct Answer)
C. Anaphase
D. Prophase

Explanation: ### Explanation **Correct Option: B. Metaphase** The primary goal of karyotyping is to visualize chromosomes clearly to detect numerical or structural abnormalities. During the **metaphase** of mitosis, chromosomes reach their maximum level of condensation, making them thick, distinct, and easily identifiable under a light microscope. **Colchicine** (or its synthetic analog, colcemid) is a spindle poison that acts by inhibiting **microtubule polymerization**. By preventing the formation of the mitotic spindle apparatus, the cell cannot transition from metaphase to anaphase. Consequently, the dividing cells are "arrested" in metaphase, allowing for the collection of a large population of cells with visible, paired sister chromatids. **Why other options are incorrect:** * **Prophase (D):** Chromosomes are just beginning to condense and are still surrounded by the nuclear envelope, making them too thin and tangled for clear analysis. * **Anaphase (C):** Once the cell enters anaphase, sister chromatids separate and move toward opposite poles. Karyotyping requires the chromosomes to be intact (paired chromatids) for proper identification. * **Telophase (A):** Chromosomes begin to de-condense back into chromatin and the nuclear envelope reforms, making individual chromosome identification impossible. ### High-Yield Clinical Pearls for NEET-PG * **Sample Collection:** For a postnatal karyotype, **peripheral blood T-lymphocytes** are most commonly used. They are stimulated to divide using a mitogen like **Phytohemagglutinin (PHA)**. * **Giemsa Stain (G-banding):** This is the most common staining technique used after metaphase arrest to create the characteristic light and dark band patterns. * **Colchicine in Medicine:** Beyond the lab, colchicine is used clinically to treat **Gout** (by inhibiting neutrophil migration) and **Familial Mediterranean Fever**. * **Aneuploidy Detection:** Karyotyping is the gold standard for diagnosing conditions like Down Syndrome (Trisomy 21), Turner Syndrome (45, XO), and Klinefelter Syndrome (47, XXY).

Question 497: The human insulin gene receptor is located on which chromosome?

A. 11 (Correct Answer)
B. 15
C. 19
D. 21

Explanation: **Explanation:** The human **insulin gene (INS)** is located on the **short arm of chromosome 11 (11p15.5)**. This is a high-yield fact in medical biochemistry, as insulin is the primary hormone regulating glucose homeostasis. It is synthesized by the beta cells of the pancreatic islets of Langerhans as preproinsulin, which is then processed into proinsulin and finally active insulin and C-peptide. **Analysis of Options:** * **A. Chromosome 11 (Correct):** Houses the insulin gene (*INS*). Additionally, the gene for the **beta-globin chain** of hemoglobin is also located on chromosome 11, making it a "hotspot" for metabolic and hematologic disorders. * **B. Chromosome 15:** Associated with conditions like Marfan syndrome (Fibrillin-1 gene), Prader-Willi, and Angelman syndromes. * **C. Chromosome 19:** This is a common distractor. While the insulin gene is on chromosome 11, the **Insulin Receptor gene (INSR)** is located on **chromosome 19 (19p13.2)**. Mutations here lead to severe insulin resistance syndromes like Donohue syndrome (Leprechaunism). * **D. Chromosome 21:** Famous for Down Syndrome (Trisomy 21) and the Amyloid Precursor Protein (APP) gene associated with Alzheimer’s disease. **NEET-PG High-Yield Pearls:** * **Insulin Gene:** Chromosome 11. * **Insulin Receptor Gene:** Chromosome 19. * **Glut-4:** The insulin-dependent glucose transporter is primarily found in skeletal muscle and adipose tissue. * **C-peptide:** Secreted in equimolar amounts with insulin; used as a marker for endogenous insulin production (distinguishes Type 1 DM from Type 2 DM or exogenous insulin surreptitious use).

Question 498: Which of the following statements about peptidyl transferase is true?

A. It is used in elongation and causes the attachment of the peptide chain to the A-site of tRNA. (Correct Answer)
B. It is used in elongation and causes the attachment of the peptide chain to the P-site of tRNA.
C. It is used in initiation and causes 43S complex formation.
D. It is used in initiation and causes 48S complex formation.

Explanation: **Peptidyl transferase** is a ribozyme (catalytic RNA) located within the large ribosomal subunit (28S rRNA in eukaryotes, 23S rRNA in prokaryotes). It plays a central role during the **elongation phase** of translation. ### Why Option A is Correct During elongation, the growing polypeptide chain is attached to the tRNA in the **P-site** (Peptidyl site). When a new aminoacyl-tRNA enters the **A-site** (Aminoacyl site), peptidyl transferase catalyzes the formation of a peptide bond. It breaks the bond between the polypeptide and the P-site tRNA and transfers the entire chain onto the amino acid attached to the **A-site tRNA**. Consequently, the peptide chain is momentarily attached to the A-site before translocation occurs. ### Why Other Options are Incorrect * **Option B:** This is the state *before* the enzyme acts. Peptidyl transferase specifically moves the chain *away* from the P-site to the A-site. * **Options C & D:** Peptidyl transferase is not involved in the initiation phase. The **43S pre-initiation complex** (40S subunit + eIFs + Met-tRNA) and the **48S initiation complex** (43S + mRNA) are formed well before the first peptide bond is created. ### High-Yield Clinical Pearls for NEET-PG * **Ribozyme Nature:** Peptidyl transferase is not a protein; it is an integrated part of the rRNA (28S in eukaryotes). * **Antibiotic Target:** Several antibiotics inhibit this enzyme in bacteria (23S rRNA). A classic example is **Chloramphenicol**, which can lead to bone marrow suppression (Gray baby syndrome) due to its effect on mitochondrial ribosomes. * **Direction of Synthesis:** Protein synthesis occurs from the **N-terminal to the C-terminal** end. * **Energy Source:** While peptide bond formation itself is catalyzed by the ribozyme, the overall process of elongation and translocation requires **GTP**.

Question 499: Which of the following is true about telomerase?

A. Ribonucleoprotein (Correct Answer)
B. Transcriptional factor activation
C. Membrane receptor
D. DNA binding domain

Explanation: **Explanation:** **Telomerase** is a specialized enzyme responsible for maintaining the length of telomeres (the repetitive TTAGGG sequences at the ends of eukaryotic chromosomes). It functions as a **Ribonucleoprotein (RNP)** complex, meaning it consists of both protein and RNA components. 1. **Why Option A is Correct:** Telomerase contains two essential components: * **TERT (Telomerase Reverse Transcriptase):** The catalytic protein component. * **TERC (Telomerase RNA Component):** An integral RNA molecule that acts as a **template** for synthesizing telomeric DNA. Because it uses its own RNA template to synthesize DNA, telomerase is classified as an **RNA-dependent DNA polymerase**. 2. **Why Other Options are Incorrect:** * **Option B:** Telomerase is an enzyme involved in DNA replication, not a transcription factor. Transcription factors regulate the synthesis of mRNA from DNA. * **Option C:** It is a nuclear enzyme, not a membrane-bound receptor. * **Option D:** While it interacts with DNA, "DNA binding domain" is a structural motif characteristic of transcription factors or histones; telomerase is defined primarily by its catalytic reverse transcriptase activity. **High-Yield Clinical Pearls for NEET-PG:** * **The End-Replication Problem:** DNA polymerase cannot replicate the 3' end of linear chromosomes, leading to progressive shortening. Telomerase solves this. * **Cancer & Aging:** Telomerase activity is high in **germ cells, stem cells, and cancer cells** (conferring "immortality"), but is low or absent in most somatic cells (leading to cellular senescence). * **Prokaryotes:** Do not have telomerase because their DNA is **circular** and lacks ends.

Question 500: Which of the following toxins inhibits the peptidyl transferase?

A. Ricin (Correct Answer)
B. Diphtheria toxin
C. Pertussis toxin
D. Amanitin

Explanation: **Explanation:** The correct answer is **Ricin**. Ricin is a potent toxin derived from the seeds of the castor oil plant (*Ricinus communis*). It acts as a **Type II Ribosome-Inactivating Protein (RIP)**. **1. Why Ricin is correct:** Ricin functions as an **N-glycosidase** that specifically removes a single adenine residue from the 28S ribosomal RNA of the 60S eukaryotic ribosomal subunit. This site is part of the "sarcin/ricin loop," which is critical for the binding of elongation factors. By depurinating this specific adenine, Ricin irreversibly damages the ribosome, preventing it from facilitating **peptidyl transferase activity** and binding elongation factors, thereby halting protein synthesis. **2. Why other options are incorrect:** * **Diphtheria toxin:** Inhibits protein synthesis by catalyzing the ADP-ribosylation of **Elongation Factor-2 (eEF-2)**, not by targeting peptidyl transferase directly. * **Pertussis toxin:** Acts by ADP-ribosylating the **Gi (inhibitory) protein**, leading to increased levels of cAMP; it does not directly inhibit translation. * **Amanitin (α-amanitin):** Found in *Amanita phalloides* (death cap mushroom), it specifically inhibits **RNA Polymerase II**, thereby blocking mRNA synthesis (transcription) rather than translation. **Clinical Pearls for NEET-PG:** * **Shiga Toxin:** Produced by *S. dysenteriae*, it shares the same mechanism as Ricin (cleaving the 28S rRNA). * **Cycloheximide:** A laboratory tool that specifically inhibits eukaryotic peptidyl transferase. * **Chloramphenicol:** Inhibits **prokaryotic** (70S) peptidyl transferase; its side effect is bone marrow suppression due to its effect on mitochondrial ribosomes. * **Mnemonic for Ricin:** **R**icin **R**emoves **R**ibosomal adenine.

Practice by Chapter

DNA Replication and Repair Mechanisms

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Transcription Factors and Gene Regulation

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Epigenetics and DNA Methylation

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RNA Processing and Splicing

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miRNA and RNA Interference

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Protein Synthesis and Post-Translational Modifications

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Genomics and Human Genome Project

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Single Nucleotide Polymorphisms

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Gene Therapy Approaches

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CRISPR-Cas9 and Genome Editing

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DNA Fingerprinting and Forensics

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Molecular Basis of Genetic Diseases

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