Single Nucleotide Polymorphisms — MCQs
Gene not involved in SCID:
Which of the following statements accurately describes a gene library?
Which of the following is used to detect abnormal gene sequences EXCEPT?
Which type of mutation can act as a suppressor to restore the wild-type phenotype in organisms carrying a mutant gene?
Which of the following statements about polymorphism is true?
Which of the following techniques can be used to detect single base pair substitutions?
What is the term for a single mutation in a nucleotide base pair that results in a termination codon?
Which of the following is a primarily RNA based technique?
All are added to PCR, except:
Transcription is inhibited by which of the following agents?
Single Nucleotide Polymorphisms Indian Medical PG Practice Questions and MCQs
Question 1: 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 2: Which of the following statements accurately describes a gene library?
- A. A physical library containing books about genetics.
- B. A digital database of genetic sequences.
- C. A collection of cloned DNA fragments that represent an organism's genome. (Correct Answer)
- D. A collection of DNA sequences or fragments.
Explanation: ***A collection of cloned DNA fragments that represent an organism's genome.*** - A **gene library** (also called a DNA library) is a collection of various **DNA fragments** from a genome, each carried by a vector and cloned in a host cell, so that the entire genome is represented and can be accessed. - This systematic collection ensures that essentially all the organism's **genetic material** is available for study, screening, and sequencing. *A physical library containing books about genetics.* - This statement describes a traditional **resource for genetic information**, not the molecular construct itself. - A physical library contains **printed materials** (books, journals) for reading and research, distinct from biological samples. *A digital database of genetic sequences.* - While digital databases store genetic sequence information (e.g., GenBank), they are **in silico** representations and not physical collections of DNA. - These databases are used to **analyze and retrieve genetic information**, but they are not the gene libraries themselves. *A collection of DNA sequences or fragments.* - This definition is too broad, as a gene library specifically refers to **cloned DNA fragments**. - Without the cloning and representation of an entire genome, it's merely a collection, not a structured "library" in the molecular biology sense.
Question 3: Which of the following is used to detect abnormal gene sequences EXCEPT?
- A. RFLP analysis
- B. Pyrosequencing
- C. Flow cytometry (Correct Answer)
- D. FISH
Explanation: ***Flow cytometry*** - **Flow cytometry** is primarily used to analyze **cell populations** based on their physical and biochemical characteristics (e.g., size, granularity, and protein expression) by passing them single file through a laser beam, not for direct gene sequencing. - It detects and quantifies cells labeled with **fluorescent antibodies**, making it useful for immunophenotyping, cell sorting, and DNA content analysis, but not for identifying specific gene sequences or mutations. *RFLP analysis* - **Restriction fragment length polymorphism (RFLP) analysis** detects variations in **DNA sequences** by using **restriction enzymes** to cut DNA at specific sites. - Differences in fragment lengths indicate **polymorphisms** or **mutations** within the recognition sites, thereby identifying abnormal gene sequences. *Pyrosequencing* - **Pyrosequencing** is a method of **DNA sequencing** that determines the sequence of nucleotides by detecting the release of pyrophosphate during DNA synthesis. - It is used to identify **single nucleotide polymorphisms (SNPs)** and **short genetic variations**, making it suitable for detecting abnormal gene sequences. *FISH* - **Fluorescence in situ hybridization (FISH)** uses **fluorescently labeled DNA probes** that bind to specific complementary **DNA sequences** on chromosomes. - It is a powerful cytogenetic technique for detecting **chromosomal abnormalities**, such as deletions, translocations, and amplifications, thereby identifying abnormal gene sequences.
Question 4: 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 5: Which of the following statements about polymorphism is true?
- A. Single phenotype linked to a single locus with multiple abnormal alleles.
- B. Single locus with multiple normal alleles. (Correct Answer)
- C. Single locus with multiple abnormal alleles, not linked to a specific phenotype.
- D. Single phenotype linked to a single locus with both normal and abnormal alleles.
Explanation: ***Single locus with multiple normal alleles.*** - **Polymorphism** refers to the existence of multiple alleles at a **single genetic locus** within a population. - For a variant to be considered a polymorphism, the most common allele must have a frequency of **less than 99%**, meaning at least two alleles are common. *Single locus with multiple abnormal alleles, not linked to a specific phenotype.* - While polymorphism involves multiple alleles at a single locus, classifying them as "abnormal" is misleading, as polymorphism often refers to **variations that are common** in the population and not necessarily disease-causing or abnormal. - The definition emphasizes the presence of multiple alleles, not their clinical implications, and many polymorphisms have **no overt phenotypic effect**. *Single phenotype linked to a single locus with both normal and abnormal alleles.* - Polymorphism primarily describes **genetic variation (alleles)**, not direct links to a single phenotype. A single locus can influence **multiple phenotypes**, and a single phenotype can be influenced by multiple loci. - Grouping alleles as "normal" and "abnormal" oversimplifies the concept; **many polymorphisms are neutral** or beneficial, and some "normal" alleles can become "abnormal" in certain contexts. *Single phenotype linked to a single locus with multiple abnormal alleles.* - This option incorrectly narrows the definition by focusing on a **single phenotype** and exclusively "abnormal" alleles. Polymorphism encompasses any common variation, regardless of its phenotypic effect or whether the alleles are considered abnormal. - Many polymorphic variations are **silent mutations** or variations that do not result in overt phenotypic changes or disease.
Question 6: Which of the following techniques can be used to detect single base pair substitutions?
- A. FISH
- B. Southern blot
- C. PCR (Correct Answer)
- D. Restriction Fragment Length Polymorphism (RFLP)
Explanation: ***PCR (with sequencing or allele-specific methods)*** - **PCR-based techniques** are the most versatile methods for detecting single base pair substitutions (point mutations) - **Allele-specific PCR** can directly detect known point mutations by using primers specific to mutant or wild-type alleles - **PCR followed by Sanger sequencing** is the gold standard for identifying any single base pair substitution - **High-resolution melting (HRM) analysis** after PCR can detect mutations based on melting curve differences - PCR amplification is the foundation that enables these detection methods *FISH (Fluorescence in situ hybridization)* - FISH detects **large chromosomal abnormalities** such as aneuploidy, translocations, large deletions, and duplications - It visualizes chromosomal-level changes using fluorescent probes - **Not sensitive enough** to detect single base pair changes, as these are too small to visualize cytogenetically *Southern blot* - Southern blot detects **large DNA rearrangements**, insertions, deletions, or copy number variations - Analyzes restriction enzyme fragments separated by gel electrophoresis - **Generally cannot detect** single base pair substitutions unless they create or abolish a restriction enzyme recognition site - Even when applicable, PCR-based methods are more efficient and sensitive *Restriction Fragment Length Polymorphism (RFLP)* - RFLP can detect single base pair substitutions **only if** they create or abolish a **restriction enzyme recognition site** - Classic example: **Sickle cell mutation** (GAG→GTG in β-globin gene) abolishes an MstII restriction site - **Limited applicability** - can only detect the subset of point mutations that affect restriction sites - PCR-based methods are preferred as they can detect **any** single base pair substitution, not just those affecting restriction sites
Question 7: What is the term for a single mutation in a nucleotide base pair that results in a termination codon?
- A. Missense mutation
- B. Nonsense mutation (Correct Answer)
- C. Termination mutation
- D. Silent mutation
Explanation: ***Nonsense mutation*** - A **nonsense mutation** occurs when a single nucleotide base pair change leads to the formation of a **premature stop codon**, which results in a truncated and often non-functional protein. - The term "nonsense" refers to the fact that the new codon signals an early termination of protein synthesis. *Missense mutation* - A **missense mutation** involves a single nucleotide change that results in a codon coding for a **different amino acid**, potentially altering protein function but not necessarily terminating it. - This type of mutation can have varying effects on protein function, from benign to severe, depending on the amino acid substitution. *Termination mutation* - While a nonsense mutation does result in **premature termination**, "termination mutation" is not the standard or most precise scientific term used to describe this specific type of genetic alteration. - The more accurate and widely accepted terminology is **nonsense mutation** for a change leading to a stop codon. *Silent mutation* - A **silent mutation** is a type of point mutation that changes a single nucleotide, but does not change the amino acid sequence of the protein due to the **degeneracy of the genetic code**. - These mutations have **no observable effect** on the organism's phenotype as the protein produced remains unchanged.
Question 8: Which of the following is a primarily RNA based technique?
- A. Sanger's technique
- B. Western blotting
- C. Next generation sequencing (Correct Answer)
- D. PCR
Explanation: ***Next generation sequencing*** - NGS, particularly **RNA-Seq (RNA sequencing)**, is the most advanced and comprehensive technique for studying RNA among the given options. - RNA-Seq directly sequences **RNA transcripts** to analyze gene expression, identify splice variants, detect novel transcripts, and quantify RNA abundance genome-wide. - While it involves converting RNA to cDNA for sequencing, **RNA is the primary starting material and target** of analysis, making it the most RNA-focused technique listed. - Superior to other methods for comprehensive transcriptome analysis. *Sanger's technique* - **Sanger sequencing** is a **DNA sequencing method** that determines the nucleotide sequence of DNA molecules. - Primarily designed for and used with DNA templates. - Not used for direct RNA analysis in routine practice. *Western blotting* - **Western blotting** detects and analyzes **proteins**, not nucleic acids. - Uses antibodies to identify specific proteins after electrophoretic separation. - Not related to RNA techniques. *PCR* - Standard **PCR amplifies DNA sequences** only. - While **RT-PCR** (reverse transcriptase PCR) starts with RNA, it immediately converts RNA to cDNA, and the actual amplification is DNA-based. - Less comprehensive for RNA analysis compared to RNA-Seq.
Question 9: All are added to PCR, except:
- A. Thermostable DNA polymerase
- B. Template DNA
- C. Deoxynucleotide
- D. Dideoxynucleotide (Correct Answer)
Explanation: ***Dideoxynucleotide*** - **Dideoxynucleotides (ddNTPs)** are chain-terminating nucleotides that lack a 3'-hydroxyl group, preventing further phosphodiester bond formation and DNA strand elongation. They are primarily used in **Sanger sequencing**, not standard PCR. - In PCR, the goal is to amplify DNA segments, which requires continued strand synthesis, making ddNTPs unsuitable as they would halt the amplification process. *Thermostable DNA polymerase* - **Thermostable DNA polymerase** (e.g., Taq polymerase) is a crucial component of PCR, responsible for synthesizing new DNA strands during the extension phase. - Its thermostability allows it to withstand the high temperatures used during the denaturation step in each cycle without losing activity. *Template DNA* - **Template DNA** is the specific DNA sequence that needs to be amplified, serving as the blueprint for the PCR reaction. - The primers anneal to the template DNA, dictating the region that will be copied. *Deoxynucleotide* - **Deoxynucleotides (dNTPs)** are the basic building blocks of DNA (dATP, dCTP, dGTP, dTTP) that are incorporated by DNA polymerase to synthesize new DNA strands. - They provide the raw materials for the "extension" phase of PCR, where the DNA polymerase adds nucleotides complementary to the template strand.
Question 10: Transcription is inhibited by which of the following agents?
- A. Actinomycin D (Correct Answer)
- B. Amanitin
- C. Chloramphenicol
- D. Streptomycin
Explanation: **Explanation:** Transcription is the process of synthesizing RNA from a DNA template. **Actinomycin D (Dactinomycin)** is a potent inhibitor of transcription in both prokaryotes and eukaryotes. It works by **intercalating between cytosine-guanine (C-G) base pairs** of the DNA template, creating a stable complex that physically blocks the movement of RNA polymerase, thereby preventing RNA chain elongation. **Analysis of Options:** * **A. Actinomycin D (Correct):** As described, it inhibits transcription by DNA intercalation. Clinically, it is used as a chemotherapy agent (e.g., for Wilms tumor and Ewing sarcoma). * **B. Amanitin (α-Amanitin):** While this also inhibits transcription (specifically **RNA Polymerase II** in eukaryotes), it is derived from the *Amanita phalloides* mushroom. In many MCQ contexts, if both are present, Actinomycin D is the classic general inhibitor cited for its action on the DNA template itself. (Note: Some sources consider both correct; however, Actinomycin D is the universal inhibitor for both cell types). * **C. Chloramphenicol:** This is a **translation (protein synthesis) inhibitor**. It binds to the **50S ribosomal subunit** of bacteria, inhibiting peptidyl transferase. * **D. Streptomycin:** This is an aminoglycoside that inhibits **translation** by binding to the **30S ribosomal subunit**, causing misreading of mRNA and inhibiting the initiation of protein synthesis. **High-Yield Clinical Pearls for NEET-PG:** * **Rifampicin:** Inhibits bacterial transcription by binding to the **beta-subunit of DNA-dependent RNA polymerase**. * **α-Amanitin:** Found in "Death Cap" mushrooms; causes severe hepatotoxicity by halting mRNA synthesis. * **Prokaryotic vs. Eukaryotic Inhibition:** Always distinguish if a drug acts on the 30S/50S (Prokaryotic translation) or 40S/60S (Eukaryotic translation) subunits.
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