Gene Therapy Approaches — MCQs
The mechanism of genetic transfer where a phage serves as a vehicle is:
Gene not involved in SCID:
Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
Which of the following statements about gene therapy is false?
Phenotypic expression of a gene depending on the parent of origin is referred to as:
When a gene is expressed exclusively from the allele inherited from one parent while the allele from the other parent is silenced, what is this phenomenon known as?
Gene amplification is achieved through
What is the technique for accurate quantification of gene expression?
Which type of mutation can act as a suppressor to restore the wild-type phenotype in organisms carrying a mutant gene?
Which type of mutation results in the reversal to the wild type of phenotype when the mutant gene is suppressed?
Gene Therapy Approaches Indian Medical PG Practice Questions and MCQs
Question 1: The mechanism of genetic transfer where a phage serves as a vehicle is:
- A. Transformation
- B. Lysogeny
- C. Transduction (Correct Answer)
- D. Conjugation
Explanation: ***Transduction*** - This is the correct answer as **transduction** is the process of genetic transfer where a **bacteriophage** (a virus that infects bacteria) serves as a vehicle to transfer **bacterial DNA** from one bacterium to another. - This process can be **generalized transduction**, where any bacterial gene can be transferred, or **specialized transduction**, where only specific genes near the prophage integration site are transferred. *Transformation* - **Transformation** is a type of horizontal gene transfer where bacteria take up **naked DNA** from their environment. - This process does **not involve a phage** and is especially common in naturally competent bacteria like Streptococcus pneumoniae and Haemophilus influenzae. *Conjugation* - **Conjugation** is the process where genetic material is directly transferred between two bacterial cells through a **pilus** (sex pilus). - This typically involves the transfer of **plasmids** and does not involve a viral vehicle. *Lysogeny* - **Lysogeny** refers to a cycle in which a **bacteriophage** integrates its **genome** into the host bacterium's chromosome as a **prophage** without immediately causing lysis. - While it involves a phage, it describes the *state* of the phage-host relationship rather than a method of gene transfer *between different bacteria* via a phage vehicle.
Question 2: Gene not involved in SCID:
- A. BTK (Correct Answer)
- B. ZAP70
- C. IL2RG
- D. JAK3
Explanation: ***BTK*** - **Bruton's tyrosine kinase (BTK)** is associated with **X-linked agammaglobulinemia (XLA)**, a primary immunodeficiency characterized by the absence of mature B cells and significantly reduced antibody production. While it causes severe immune deficiency, it is not a direct cause of **SCID**. - XLA results in recurrent bacterial infections due to an inability to produce antibodies, rather than the severe combined T and B cell dysfunction seen in SCID. *ZAP70* - **ZAP70** deficiency is a cause of **SCID**. It leads to impaired T-cell receptor signaling, resulting in profound functional T-cell lymphopenia. - Patients with ZAP70 deficiency have normal numbers of CD4 T cells but very low or absent CD8 T cells, and their T cells are functionally impaired, leading to severe immunodeficiency. *IL2RG* - The **IL2RG** gene encodes the common gamma chain (γc), a crucial component of several **interleukin receptors (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21)**. [1] - Mutations in IL2RG cause **X-linked SCID (X-SCID)**, the most common form of SCID, leading to a block in T-cell and NK-cell development due to defective cytokine signaling. [1] *JAK3* - **Janus kinase 3 (JAK3)** is a tyrosine kinase that associates with the **common gamma chain (γc)** and is essential for cytokine signaling downstream of the γc-containing receptors. [1] - **JAK3 deficiency** results in an **autosomal recessive form of SCID**, clinically indistinguishable from X-SCID, with impaired T-cell and NK-cell development due to defective cytokine signaling. [1] **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 247-248.
Question 3: Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
- A. Gene Knockout
- B. Impaired DNA repair
- C. Genomic Imprinting (Correct Answer)
- D. RNA interference
Explanation: ***Genomic Imprinting*** - **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. - In Prader-Willi syndrome, the disease results from the loss of function of specific genes on chromosome 15 (15q11-q13) inherited from the father, while Angelman syndrome results from the loss of function of a different gene (UBE3A) in the same region, but inherited from the mother. *RNA interference* - **RNA interference** is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. - This process is not directly responsible for the parent-of-origin-specific expression patterns observed in these syndromes. *Gene Knockout* - A **gene knockout** is a genetic technique in which an organism's genes are made inoperative. - While it involves modifying gene function, it does not explain the differential expression based on parental origin. *Impaired DNA repair* - **Impaired DNA repair** refers to defects in the mechanisms that correct DNA damage. - This can lead to increased mutations and conditions like cancer, but it is not the underlying mechanism for Prader-Willi or Angelman syndromes.
Question 4: Which of the following statements about gene therapy is false?
- A. Gene also considered as drug
- B. Gene therapy can be used to treat some cancers.
- C. Has been tried in cystic fibrosis
- D. Gene therapy is only used for genetic disorders. (Correct Answer)
Explanation: ***Gene therapy is only used for genetic disorders.*** - This statement is **false** because gene therapy has applications beyond just genetic disorders. It is also being explored and used in the treatment of acquired diseases such as **cancer** and **infectious diseases**. - While it's a prominent approach for correcting genetic defects, its scope is much broader, involving the introduction or modification of genes to achieve a therapeutic effect in various conditions. *Gene also considered as drug* - This statement is **true**. Gene therapy products are often regulated as **drugs** or **biological products** by regulatory bodies like the FDA. - This is because they involve the delivery of genetic material that acts to modify gene expression or cell function to produce a therapeutic effect, similar to how traditional drugs work. *Has been tried in cystic fibrosis* - This statement is **true**. Gene therapy has been extensively investigated as a potential treatment for **cystic fibrosis (CF)**. - CF is caused by mutations in the **CFTR gene**, and researchers have attempted to deliver functional copies of this gene to the affected cells, particularly in the lungs, to correct the underlying defect. *Gene therapy can be used to treat some cancers.* - This statement is **true**. Gene therapy is an active area of research and treatment for various **cancers** [1]. - Approaches include introducing genes that make cancer cells more susceptible to chemotherapy, enhancing the immune system's ability to fight cancer, or directly killing cancer cells through gene delivery [1].
Question 5: Phenotypic expression of a gene depending on the parent of origin is referred to as:
- A. Genomic imprinting (parent-of-origin gene expression) (Correct Answer)
- B. Mosaic genetic variation
- C. Nonpenetrance of genotype
- D. Genetic anticipation
Explanation: ***Genomic imprinting (parent-of-origin gene expression)*** - **Genomic imprinting** is an epigenetic phenomenon where gene expression is dependent on whether the gene was inherited from the mother or the father. - This results in monoallelic expression of specific genes, with only one copy (maternal or paternal) being active. *Mosaic genetic variation* - **Mosaicism** refers to the presence of two or more populations of genetically different cells in one individual, all derived from a single zygote. - This typically arises from a somatic mutation during development, not from differential expression based on parental origin. *Nonpenetrance of genotype* - **Nonpenetrance** occurs when individuals carrying a disease-causing genotype do not express the associated phenotype. - This concept relates to the presence or absence of a phenotype, not the differential expression based on parental origin. *Genetic anticipation* - **Genetic anticipation** is the phenomenon where the symptoms of a genetic disorder become more severe and/or appear at an earlier age in successive generations. - This is commonly observed in disorders caused by expansions of trinucleotide repeats, such as Huntington's disease, and is distinct from parent-of-origin gene expression.
Question 6: When a gene is expressed exclusively from the allele inherited from one parent while the allele from the other parent is silenced, what is this phenomenon known as?
- A. Genomic imprinting (Correct Answer)
- B. Mosaicism
- C. Alleles
- D. Chimerism
Explanation: ***Genomic imprinting*** - **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. - This means that depending on whether the gene was inherited from the **mother or the father**, only one copy (maternal or paternal) is expressed, while the other is silenced. *Mosaicism* - **Mosaicism** describes the presence of **two or more cell lines** with different genotypes within a single individual, originating from a single zygote. - This typically arises from a **post-zygotic mutation** or chromosomal abnormality during early embryonic development. *Alleles* - **Alleles** are different forms of a **single gene** located at the same locus on homologous chromosomes. - An individual inherits **two alleles** for each gene, one from each parent, but both are usually expressed unless one is recessive. *Chimerism* - **Chimerism** refers to an individual composed of cells from **two or more different zygotes**, meaning the cells originate from different genetic lineages. - This can occur through processes like **fusion of two embryos** or organ transplantation.
Question 7: Gene amplification is achieved through
- A. Polymerase Chain Reaction (Correct Answer)
- B. DNA strand hybridization
- C. In situ DNA hybridization
- D. Ligase chain reaction (LCR)
Explanation: ***Polymerase Chain Reaction*** - **PCR** is the **gold standard** molecular biology technique that generates **millions to billions of copies** of a specific DNA segment over a short period. - It utilizes a cyclical process of **denaturation**, **annealing**, and **extension** with **thermostable DNA polymerase** to achieve exponential amplification. - **Most widely used** method for gene amplification in research and diagnostics. *DNA strand hybridization* - **DNA strand hybridization** is the process where two complementary single-stranded DNA molecules bind together to form a **double-stranded molecule**. - This process is fundamental to many molecular techniques but does not, in itself, achieve **amplification**; rather, it is a **binding event**. *In situ DNA hybridization* - **In situ hybridization** is a technique that localizes and detects specific **nucleic acid sequences** (DNA or RNA) within cells or tissues directly on a slide. - While it uses **hybridization**, its primary purpose is **detection and localization**, not the **amplification** of DNA sequences. *Ligase chain reaction (LCR)* - **LCR** is a molecular technique that does amplify DNA sequences exponentially using **DNA ligase** to join adjacent oligonucleotide probes. - However, it is **less commonly used** than PCR, has more **stringent requirements** (requires knowledge of both strands), and is primarily used for detecting **known point mutations** rather than general gene amplification. - **PCR remains the standard** technique when the question refers to gene amplification without additional qualifiers.
Question 8: What is the technique for accurate quantification of gene expression?
- A. PCR
- B. Real-Time Reverse Transcriptase PCR (Correct Answer)
- C. Reverse Transcriptase PCR
- D. Northern blot
Explanation: ***Real-Time Reverse Transcriptase PCR*** - This technique allows for the **quantification of gene expression** by concurrently reverse-transcribing RNA to cDNA and amplifying it while monitoring the accumulation of DNA in real-time using fluorescent reporters. - The ** threshold cycle (Ct) value** is inversely proportional to the initial amount of target mRNA, enabling precise quantification. *Northern blot* - This method is used to detect **RNA sequences** and can provide semi-quantitative data about gene expression levels based on band intensity. - However, it is generally **less sensitive** and provides less precise quantification compared to real-time PCR. *PCR* - **Standard PCR** amplifies DNA, but it is not directly used for gene expression quantification as it starts with DNA templates. - While it can be used to detect the presence of a gene, it does not quantify its expression without further modifications or additional steps like reverse transcription and real-time monitoring. *Reverse Transcriptase PCR* - This technique involves **reverse transcribing RNA into cDNA** and then performing standard PCR to amplify the cDNA. - While it confirms the presence of mRNA and allows for cDNA amplification, it is a **qualitative or semi-quantitative** method for expression, as the endpoint detection does not accurately reflect initial mRNA concentration due to plateau effects.
Question 9: Which type of mutation can act as a suppressor to restore the wild-type phenotype in organisms carrying a mutant gene?
- A. Frameshift mutation of coding gene
- B. Mutation of tRNA (Correct Answer)
- C. Deletion of mutant gene
- D. Addition of another normal gene
Explanation: ***Mutation of tRNA*** - A **tRNA suppressor mutation** can alter its anticodon, allowing it to recognize a **stop codon** (nonsense suppressor) or a missense codon, and insert an amino acid, thereby suppressing the original mutation. - This is a classic example of an **intergenic suppressor mutation** that acts at a different genetic locus from the original mutation. - These suppressors are particularly effective for **nonsense mutations** (premature stop codons) and certain missense mutations by correcting the decoding error during translation. *Frameshift mutation of coding gene* - A single frameshift mutation causes a shift in the **reading frame**, leading to a completely different protein sequence downstream and often a premature stop codon, which would worsen the phenotype. - While a **second compensating frameshift** mutation in the same gene could theoretically restore the reading frame (acting as an intragenic suppressor), this is context-dependent and less reliable than tRNA suppressors. - The question asks for mutations that "can act as a suppressor," and **tRNA mutations are the more universally recognized and reliable suppressor mechanism** in classical genetics. *Deletion of mutant gene* - **Deleting the mutant gene** removes the genetic information entirely but does not restore wild-type function; instead, it typically results in **loss of function** or complete absence of the protein. - This would lead to a **null phenotype** rather than restoration of wild-type phenotype, especially if the gene is essential. *Addition of another normal gene* - The **addition of another normal (wild-type) gene copy** provides a functional protein that can compensate for the mutant gene's deficiency. - While this can restore a wild-type phenotype, it represents **gene complementation** or gene therapy, not a true suppressor mutation that modifies the interpretation or expression of the existing mutant allele.
Question 10: Which type of mutation results in the reversal to the wild type of phenotype when the mutant gene is suppressed?
- A. Addition of another normal gene
- B. Frameshift mutation of coding gene
- C. Mutation of tRNA (Correct Answer)
- D. Deletion of mutant gene
Explanation: ***Mutation of tRNA*** - A mutation in the **tRNA molecule** can lead to the insertion of an **incorrect amino acid** at a premature stop codon, effectively "reading through" the stop codon and suppressing the original mutation. - This suppressor tRNA then allows for the production of a full-length, functional protein, thereby reversing the phenotypic effect of the initial mutation. *Addition of another normal gene* - Adding a normal gene would introduce a **functional copy** without directly reversing or suppressing the original mutation at the molecular level of the existing mutant gene. - While it could restore function, it doesn't represent a "suppression" of the mutant gene itself but rather a **complementary expression**. *Frameshift mutation of coding gene* - A frameshift mutation leads to an **altered reading frame** and typically results in a completely different protein sequence or a premature stop codon, severely impacting protein function. - While a second, compensatory frameshift mutation could theoretically restore the reading frame, this is a **direct reversal** of the mutation, not a suppression where the original mutation is still present but its effect is negated by another mutation. *Deletion of mutant gene* - Deleting the mutant gene would **remove the source** of the abnormal phenotype entirely, rather than suppressing its effect while the gene is still present. - This is a form of correction or removal, not a suppression mechanism where another mutation counteracts the effect of the first.
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