Molecular Biology and Genomics Practice Questions

Q: Analyze the following pedigree and give the mode of inheritance:

Mitochondrial inheritance. ***Mitochondrial inheritance*** - Shows **maternal transmission** to all offspring regardless of sex, as mitochondrial DNA is inherited exclusively from the mother through the **cytoplasm of the ovum**. - Affects **both males and females equally** with no paternal transmission, which is characteristic of **extranuclear inheritance** patterns. *Autosomal recessive* - Would show **horizontal pattern** with affected siblings having unaffected parents, and **consanguinity** increasing risk. - Requires **two mutated copies** of the gene, showing **25% recurrence risk** in each pregnancy from carrier parents. *Autosomal dominant* - Would demonstrate **vertical transmission** through generations with **affected parent** typically having affected offspring. - Shows **50% recurrence risk** and affects **both sexes equally**, but with paternal transmission possible. *X-linked dominant* - Would show **affected males** passing the trait to **all daughters** but **no sons**, creating a distinctive pattern. - **Affected females** would have a **50% chance** of passing the trait to children of both sexes, with more severe manifestation in males.

Q: Which of the following enzymes is part of DNA dependent RNA polymerase?

Primase. **Explanation:** The correct answer is **Primase**. **Why Primase is the correct answer:** DNA replication cannot be initiated *de novo* because DNA polymerases require a free 3'-OH group to add nucleotides. To overcome this, the enzyme **Primase** (specifically DnaG in prokaryotes) synthesizes a short stretch of RNA (approximately 10 nucleotides) called a **primer**. Since Primase uses a DNA template to synthesize an RNA strand, it is biochemically classified as a **DNA-dependent RNA polymerase**. Once the primer is in place, DNA polymerase III can begin elongation. **Analysis of Incorrect Options:** * **DNA ligase:** This enzyme joins DNA fragments (like Okazaki fragments) by catalyzing the formation of phosphodiester bonds. It does not synthesize RNA. * **DNA polymerase III:** This is a DNA-dependent **DNA** polymerase. It synthesizes DNA by adding deoxyribonucleotides, but it cannot initiate synthesis without a primer. * **RNA transcriptase:** This term is often confused with RNA polymerase used in transcription. While RNA polymerase is also a DNA-dependent RNA polymerase, "Primase" is the specific enzyme integrated into the replisome during DNA replication. **Clinical Pearls & High-Yield Facts for NEET-PG:** * **Prokaryotes vs. Eukaryotes:** In eukaryotes, the primase activity is associated with **DNA Polymerase α** (alpha). * **Directionality:** Primase synthesizes the primer in the **5' to 3'** direction. * **Requirement:** The leading strand requires only one primer, whereas the lagging strand requires multiple primers (one for each Okazaki fragment). * **Removal:** In prokaryotes, RNA primers are removed by **DNA Polymerase I** (via its 5' to 3' exonuclease activity), not by Primase.

Q: Which of the following is a protein that is rich in basic amino acids and that functions in the packaging of DNA in chromosomes?

Histone. **Explanation:** **Histones** are the correct answer because they are specialized proteins responsible for the first level of DNA organization. DNA is negatively charged due to its phosphate backbone. To package this long molecule into the compact nucleus, it wraps around histones, which are highly **basic proteins** rich in **Arginine and Lysine**. These basic amino acids carry positive charges at physiological pH, allowing for high-affinity ionic bonding with the negatively charged DNA. This DNA-protein complex forms the **nucleosome**, the fundamental repeating unit of chromatin. **Analysis of Incorrect Options:** * **Collagen:** This is the most abundant structural protein in the extracellular matrix (ECM). While it is rich in Glycine, Proline, and Hydroxyproline, it does not bind DNA or function in genomic packaging. * **Fibrinogen:** A high-molecular-weight plasma glycoprotein synthesized in the liver. It is a clotting factor (Factor I) converted to fibrin during the coagulation cascade; it has no role in nuclear organization. * **Hyaluronic acid binding protein:** These are proteins (like CD44) that interact with hyaluronan in the ECM to regulate cell adhesion and signaling, rather than DNA packaging. **High-Yield NEET-PG Pearls:** * **Nucleosome Core:** Consists of an octamer of two molecules each of **H2A, H2B, H3, and H4**. * **Linker Histone:** **H1** is the "linker histone" that binds the entry/exit sites of DNA on the nucleosome to stabilize higher-order chromatin structures. * **Epigenetics:** Histone tails undergo post-translational modifications (Acetylation, Methylation, Phosphorylation). **Acetylation** (by HATs) neutralizes the positive charge, relaxing chromatin (Euchromatin) and increasing transcription.

Q: Prenatal diagnosis of Hemophilia is best done by?

PCR. **Explanation:** **Hemophilia A and B** are X-linked recessive disorders caused by mutations in the Factor VIII and Factor IX genes, respectively. **Why PCR is the Correct Answer:** Polymerase Chain Reaction (PCR) is the gold standard for prenatal diagnosis because it allows for the **rapid amplification of fetal DNA** obtained via Chorionic Villus Sampling (CVS) or amniocentesis. Once amplified, specific techniques like **Reverse Transcriptase-PCR (RT-PCR)** or **Direct Mutation Analysis** can identify the exact genetic defect (e.g., the common Intron 22 inversion in Hemophilia A). It is preferred due to its high sensitivity, specificity, and the small amount of fetal sample required. **Analysis of Other Options:** * **Linkage Analysis:** This was historically used when the specific mutation was unknown. It tracks the disease gene using polymorphic markers (RFLPs). However, it requires DNA from multiple family members and is prone to errors due to genetic recombination. * **Cytometry (Flow Cytometry):** This is used for analyzing physical and chemical characteristics of cells (e.g., immunophenotyping in leukemia). It cannot detect single-gene mutations required for hemophilia diagnosis. * **Microarray:** While useful for detecting chromosomal imbalances (Copy Number Variations), it is not the primary tool for the point mutations or inversions typically seen in Hemophilia. **Clinical Pearls for NEET-PG:** * **Most common mutation in severe Hemophilia A:** Intron 22 inversion. * **Gold standard for carrier detection:** DNA analysis (PCR-based). * **Prenatal sampling timing:** CVS is usually done at 10–12 weeks; Amniocentesis at 15–18 weeks. * **Factor levels:** Prenatal diagnosis via fetal blood sampling (cordocentesis) to check factor levels is rarely done now due to the high risk of fetal loss compared to PCR.

Q: Where does miRNA typically bind to facilitate gene knockdown?

3' untranslated region. ### Explanation **1. Why Option A is Correct:** MicroRNAs (miRNAs) are small, non-coding RNA molecules (typically 21–25 nucleotides) that play a crucial role in post-transcriptional gene regulation. To facilitate gene knockdown, the miRNA incorporates into the **RNA-induced silencing complex (RISC)**. The "seed sequence" (nucleotides 2–7) of the miRNA then undergoes complementary base pairing primarily with the **3' Untranslated Region (3' UTR)** of the target messenger RNA (mRNA). This binding leads to either **translational repression** (if binding is partially complementary) or **mRNA degradation** (if binding is perfectly complementary), effectively silencing the gene. **2. Why Other Options are Incorrect:** * **Option B (5' UTR):** While some rare interactions occur here, the 5' UTR is primarily involved in the initiation of translation (ribosome loading). miRNA binding here is not the standard mechanism for gene knockdown. * **Option C (Introns):** Introns are non-coding sequences removed during splicing in the nucleus. miRNA-mediated silencing occurs in the **cytoplasm** on mature, processed mRNA. * **Option D:** Although experimental evidence shows occasional binding at the 5' UTR, the **canonical and most efficient site** for miRNA-mediated regulation in humans is the 3' UTR. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **Origin:** miRNAs are transcribed by **RNA Polymerase II** as primary-miRNA (pri-miRNA). * **Processing Enzymes:** **Drosha** (in the nucleus) and **Dicer** (in the cytoplasm) are the key endonucleases that process miRNA. * **OncomiRs:** miRNAs that regulate oncogenes or tumor suppressor genes. For example, a decrease in **miRNA-15 and miRNA-16** is associated with Chronic Lymphocytic Leukemia (CLL). * **Therapeutic Potential:** miRNA mimics and antagomirs (inhibitors) are being researched as targeted therapies for cancer and viral infections (e.g., Hepatitis C).

Q: Which DNA polymerase is/are involved in the repair of mammalian DNA?

beta. In mammalian cells, DNA polymerases are categorized by their specific roles in replication and repair. **Correct Answer: B. beta (β)** DNA Polymerase beta is the primary enzyme involved in **Base Excision Repair (BER)**. It is a low-fidelity polymerase that lacks 3' to 5' exonuclease (proofreading) activity. Its main function is to fill short gaps (usually a single nucleotide) created during the repair of damaged bases caused by alkylation or oxidation. Because it handles "gap-filling" rather than long-strand synthesis, it is the classic "repair polymerase." **Explanation of Incorrect Options:** * **A. alpha (α):** This enzyme is responsible for **initiating** DNA replication. It possesses primase activity and synthesizes short RNA-DNA primers (i.e., the "iDNA"). It does not have proofreading activity and is not primarily a repair enzyme. * **C. gamma (γ):** This is the exclusive polymerase for **mitochondrial DNA replication** and repair. While it does repair, it is specific to the mitochondria, whereas the question refers to general mammalian (nuclear) DNA repair. * **D. epsilon (ε):** This is a high-fidelity enzyme responsible for the synthesis of the **leading strand** during nuclear DNA replication. It has 3' to 5' exonuclease activity for proofreading. **High-Yield Clinical Pearls for NEET-PG:** * **Polymerase Delta (δ):** Primarily synthesizes the **lagging strand** (Okazaki fragments). * **Mnemonic for Eukaryotic Pols:** * **α (Alpha):** Starts (Primer). * **β (Beta):** Bad (Low fidelity/Repair). * **γ (Gamma):** Global (Mitochondria). * **δ (Delta):** Delay (Lagging strand). * **ε (Epsilon):** Early (Leading strand). * **PCNA (Proliferating Cell Nuclear Antigen):** Acts as a "sliding clamp" for Pol δ and ε to increase processivity; it is a common marker for cell proliferation in pathology.

Q: Base substitution of GAC (Asp) to GAG (Glu) is an example of which type of mutation?

Point mutation. ### Explanation **1. Why Point Mutation is Correct:** A **point mutation** is a type of mutation where a single nucleotide base is changed, inserted, or deleted from a DNA or RNA sequence. In this case, the codon **GAC** (Aspartate) changes to **GAG** (Glutamate). Since only the third base (C → G) is substituted, it is a classic example of a point mutation. Specifically, this is a **missense mutation**, a sub-type of point mutation where the base substitution results in a different amino acid being incorporated into the protein. **2. Why Other Options are Incorrect:** * **B. Silent Mutation:** This occurs when a base substitution changes the codon but, due to the degeneracy of the genetic code, the **same amino acid** is produced. Since Aspartate changed to Glutamate, it is not silent. * **C. Non-sense Mutation:** This occurs when a base substitution results in a **stop codon** (UAA, UAG, or UGA), leading to premature termination of the polypeptide chain. GAG codes for Glutamate, not a stop signal. **3. NEET-PG High-Yield Clinical Pearls:** * **Transitions vs. Transversions:** A change from Purine to Purine (A↔G) or Pyrimidine to Pyrimidine (C↔T) is a **Transition**. A change from Purine to Pyrimidine (or vice versa) is a **Transversion**. (In this question, C → G is a Transversion). * **Sickle Cell Anemia:** The most high-yield clinical example of a point (missense) mutation. A single base change (GAG → GTG) leads to the substitution of **Glutamate by Valine** at the 6th position of the β-globin chain. * **Degeneracy/Wobble Hypothesis:** Most silent mutations occur at the 3rd position of the codon (the "wobble" position).

Q: Which snRNA is not a part of the spliceosome?

U3. ### Explanation The correct answer is **U3**. **1. Why U3 is the correct answer:** The **spliceosome** is a complex of small nuclear ribonucleoproteins (snRNPs) responsible for removing introns from pre-mRNA. The major spliceosome consists of five snRNAs: **U1, U2, U4, U5, and U6**. **U3** is a small nucleolar RNA (**snoRNA**), not a spliceosomal snRNA. It is located in the **nucleolus** and is primarily involved in the processing and methylation of **pre-ribosomal RNA (rRNA)**, rather than mRNA splicing. **2. Analysis of incorrect options:** * **U1:** This snRNA initiates splicing by binding to the **5' splice site** (GU sequence) of the intron. * **U2:** This snRNA binds to the **branch point sequence** (adenine residue) within the intron, a crucial step in forming the catalytic center. * **U4:** It acts as a chaperone or "masking" agent for U6. It must dissociate from the complex to allow U6 to become catalytically active. **3. NEET-PG Clinical Pearls & High-Yield Facts:** * **Autoimmune Correlation:** Antibodies against snRNPs (specifically **Anti-Smith/Anti-Sm antibodies**) are highly specific for **Systemic Lupus Erythematosus (SLE)**. * **The Splicing Mechanism:** Splicing involves two transesterification reactions, forming a characteristic **"Lariat" structure**. * **Alternative Splicing:** This process allows a single gene to code for multiple proteins (e.g., membrane-bound vs. secreted immunoglobulins), increasing proteomic diversity. * **Rule of Thumb:** All spliceosomal snRNAs are transcribed by RNA Polymerase II, except for **U6**, which is transcribed by **RNA Polymerase III**.

Question 1

Analyze the following pedigree and give the mode of inheritance:

Accepted Answer

Mitochondrial inheritance

Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked dominant

Question 2

Which of the following enzymes is part of DNA dependent RNA polymerase?

Accepted Answer

Primase

Answer

DNA ligase

Answer

DNA polymerase III

Answer

RNA transcriptase

Question 3

Which of the following is a protein that is rich in basic amino acids and that functions in the packaging of DNA in chromosomes?

Accepted Answer

Histone

Answer

Collagen

Answer

Fibrinogen

Answer

Hyaluronic acid binding protein

Question 4

An 8-year-old boy presents with failure to thrive, alopecia totalis, localized scleroderma, a small face and jaw, a "beak" nose, wrinkled skin, and stiff joints. He has a single-point mutation in a nuclear protein that is silent in terms of the protein's primary structure. How could such a mutation lead to a disease?

Accepted Answer

Creating an alternative splice site in the gene

Answer

Altering the tertiary structure of the protein

Answer

Inhibiting DNA replication

Answer

Introducing a premature stop codon into the protein

Question 5

Arrange the cyclins and CDKs in the cell cycle from G1 to S phase progression.

Accepted Answer

CDK6/Cyclin E

Answer

CDK4/Cyclin D

Answer

CDK1/Cyclin B

Answer

CDK2/Cyclin A

Question 6

Prenatal diagnosis of Hemophilia is best done by?

Accepted Answer

PCR

Answer

Linkage analysis

Answer

Cytometry

Answer

Microarray

Question 7

Where does miRNA typically bind to facilitate gene knockdown?

Accepted Answer

3' untranslated region

Answer

5' untranslated region

Answer

Introns

Answer

Both 3' and 5' untranslated regions

Question 8

Which DNA polymerase is/are involved in the repair of mammalian DNA?

Accepted Answer

beta

Answer

alpha

Answer

gamma

Answer

epsilon

Question 9

Base substitution of GAC (Asp) to GAG (Glu) is an example of which type of mutation?

Accepted Answer

Point mutation

Answer

Silent mutation

Answer

Non-sense mutation

Answer

None of the above

Question 10

Which snRNA is not a part of the spliceosome?

Accepted Answer

U3

Answer

U1

Answer

U2

Answer

U4

Molecular Biology and Genomics — MCQs

Molecular Biology and Genomics — MCQs

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