MCQ Corner - Genetics

How does the structure of DNA contribute to its stability and replication fidelity? The phosphodiester bonds provide stability, and the complementary base pairing ensures replication fidelity The hydrogen bonds between bases provide stability, and the sugar-phosphate backbone ensures replication fidelity The phosphodiester bonds provide stability, and the hydrogen bonds between bases ensure replication fidelity The sugar-phosphate backbone provides stability, and the complementary base pairing ensures replication fidelity. Answer: a. The phosphodiester bonds provide stability, and the complementary base pairing ensures replication fidelity.[1-3] Explanation The phosphodiester bonds making the phosphate-sugar backbone (3′-OH of one sugar to 5′-OH of another sugar through a phosphate group) give structural stability to the DNA. The nitrogenous bases jotting inward bind to their complementary bases on both strands by either two hydrogen bonds if they are A and T and three hydrogen bonds if it is between G and C. Replication fidelity depends on many factors. As already noted, Escherichia coli polymerase I has 3′ to 5′ as well as 5′ to 3′ exonuclease activity. The 5′ to 3′ exonuclease operates in the direction of DNA synthesis and helps remove RNA primers from Okazaki fragments. The 3′ to 5′ exonuclease operates in the reverse direction of DNA synthesis and participates in proofreading of newly synthesized DNA. Proofreading is effective because DNA polymerase requires a primer and is not able to initiate synthesis de novo. Primers that are hydrogen-bonded to the template are preferentially used, so when an incorrect base is incorporated, it is likely to be removed by the 3′ to 5′ exonuclease activity rather than being used to continue synthesis. 2. Histone acetylation is associated with what change in chromatin structure? Chromatin condensation and gene repression Chromatin decondensation and gene activation DNA methylation and gene silencing Chromatin stability and genome integrity. Answer: b. Chromatin decondensation and gene activation. Explanation Histone acetylation is a crucial posttranslational modification of histone proteins, which are key components of chromatin in eukaryotic cells. This process involves the addition of acetyl groups to lysine residues on histone tails, primarily by enzymes known as histone acetyltransferases. Histone acetylation typically correlates with transcriptional activation. The addition of acetyl groups neutralizes the positive charge on lysine residues, reducing the affinity between histones and the negatively charged DNA. This relaxed chromatin structure allows for easier access of transcriptional machinery to DNA, facilitating gene expression.[4] 3. Among the following which is false about depurination? It can be spontaneously produced Depurination can be done by adding 0.2M hydrochloric acid Depurination can be done by adding 2N sodium hydroxide Depurination may lead to cancer. Answer: c. Depurination can be done by adding 2N sodium hydroxide. Explanation By adding sodium hydroxide, denaturation of DNA is done. Depurination can be spontaneous and achieved in vitro by adding 0.2M hydrochloric acid.[5] At apurinic sites caused by depurination, the covalent structure of DNA becomes more susceptible to damage, which induces spontaneous mutagenesis, carcinogenesis, and cellular aging. 4. What is the primary function of piRNAs in the germline cells? They regulate gene expression at the transcriptional level They protect the genome from transposable elements They are involved in RNA splicing They guide DNA methylation. Answer: b. They protect the genome from transposable elements. Explanation PiRNAs, or Piwi-interacting RNAs, are a class of small noncoding RNA molecules that play crucial roles in the regulation of gene expression, particularly in germline cells (sperm and egg cells). PiRNAs are primarily involved in silencing the activity of transposable elements (TEs), also known as jumping genes, within the genome. TEs are sequences of DNA that can move or copy themselves to different positions within the genome, potentially causing mutations or disrupting gene function. PiRNAs help maintain genome stability by suppressing the expression of these TEs. In addition to their role in transposon silencing, piRNAs have also been implicated in epigenetic regulation, influencing chromatin structure and gene expression patterns in germline cells.[6] 5. In the case of mitochondrial inheritance, if a mother is affected by a mitochondrial disorder, what is the probability that her child will inherit the disorder? 0% 25% 50% 100%. Answer: d. 100%. Explanation All children of a mother with a mitochondrial disorder will inherit the disorder because mitochondria are inherited maternally.[7] 6. What is the primary mechanism of action for proteasome inhibitors in cancer therapy? They inhibit DNA synthesis They induce apoptosis by accumulating pro-apoptotic factors They directly activate death receptors They disrupt the cell cycle. Answer: b. They induce apoptosis by accumulating pro-apoptotic factors. Explanation Proteasome inhibitors are a class of drugs that block the action of proteasomes, which are enzyme complexes responsible for degrading unneeded or damaged proteins by proteolysis. This inhibition can lead to the accumulation of damaged or misfolded proteins within cells, causing stress and ultimately leading to cell death, particularly in rapidly dividing cells such as cancer cells. Proteasome inhibitors have shown effectiveness in treating certain types of cancers, most notably multiple myeloma and some lymphomas.[8] 7. An apparently healthy 14-year-old boy was undergoing tonsillectomy procedure under general anesthesia. He developed muscle rigidity and high-grade temperature and subsequently succumbed to death. The boy’s grandfather had also died during a surgical procedure. The reason of the death of the boy is most likely to be associated with which of the following? Defective Ca2+ - ATPase Defective Nm receptors Defective dihydropyridine receptors Defective ryanodine receptors. Answer: d. Defective ryanodine receptors. Explanation In malignant hyperthermia, an autosomal dominant condition, defective ryanodine receptors (RyRs) respond to certain halogenated anesthetics and open for longer time thus flooding the cytosol with calcium. This increase in calcium concentration causes continuous contraction of the muscles. The result is increased body temperature, muscle rigidity, and increased anaerobic metabolism. In contrast, dihydropyridine receptors are activated by the skeletal muscle fiber action potential, but they are not affected by halogenated anesthetics. Anesthetic agents implicated in malignant hyperthermia are halothane, isoflurane, sevoflurane, and skeletal muscle relaxant succinylcholine. Administration of dantrolene (RyR antagonist) along with other measures are the mainstay of treatment.[9,10] 8. Among 500 patients on anti-tuberculosis therapy, 400 were slow acetylators (a) and 100 were rapid acetylators (b) in a study on N-acetyltransferase (NAT) 2 gene polymorphism. Regarding the development of peripheral neuropathy which of the following sentences is correct? More frequently expected in Group B than in Group A More frequently expected in Group A than in Group B Can be prevented by Vitamin B12 prophylaxis Both A and C. Answer: b. More frequently expected in Group A than Group B. Explanation Metabolism of isoniazid by liver NAT is genetically determined. In slow acetylators, both the average plasma concentration of the drug and plasma half-life are more compared to rapid acetylators. Peripheral neuropathy as an adverse effect to isoniazid is more likely to occur in the slow acetylator group and other predisposing factors are alcohol use, diabetes mellitus, and AIDS. It is mostly due to pyridoxine (Vitamin B6 deficiency).[11,12] 9. The two-hit hypothesis was proposed by which scientist? James Watson Alfred Knudson Francis Crick Robert Weinberg. Answer: b. Alfred Knudson. Explanation The two-hit hypothesis, proposed by Knudson,[13] suggests that cancer is the result of accumulated genetic mutations. In the context of hereditary cancers, the first “hit” is often a germline mutation present in every cell of the body, and the second “hit” is a somatic mutation that occurs in specific cells, leading to cancer development. James Watson and Crick elucidated the double helical structure of DNA. The concept was initially suggested by Rosalind Franklin and Maurice Wilkins. Rosalind Franklin was a skilled X-ray crystallographer and her work was pivotal in elucidating the structure of DNA. Robert Weinberg is widely known for his contribution to cancer research in terms of discovering the first human oncogene and the first tumor suppressor gene. 10. Physical integration with a bacterial replicon is required in replication, in which of the following? Double-stranded DNA bacteriophage Single-stranded DNA bacteriophage Single-stranded RNA bacteriophage Transposon. Answer: d. Transposon. Explanation Transposons are not self-replicating and are dependent on chromosomal or plasmid DNA for replication. A replicon is a region of an organism’s genome which is independently replicated from a single ori or origin of replication. This is a single site for prokaryotes but multiple in cases of eukaryotic genome. Transposons or TEs are the bacterial genes that are capable of intracellular transfer between chromosome to chromosome, plasmid to plasmid, and chromosome to plasmid or vice versa and the process of such intracellular transfer of transposons is called transposition. Noncellular entities such as viruses, viroid, virusoids, plasmids, transposons, and retrotransposons also can behave as replicons. However, transposons differ from primary events and hence can be considered the best option here.[14] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.