Molecular Basis of Disease — MCQs

10 questions

Sumoylation of histone proteins is associated with

Mutations are due to changes in:

An affected male does not have affected children but an affected female always has affected children. Type of inheritance?

Differential expression of the same gene depending on parent of origin is referred to as

Which of the following is a primarily RNA based technique?

In which type of lung carcinoma is the p53 mutation most commonly observed?

Which one of the following is an autosomal dominant disorder?

An electron microscopy of muscle biopsy shows 'parking lot' appearance. Which additional finding would confirm myotonic dystrophy?

BCR-ABL fusion gene is MOST CHARACTERISTICALLY seen in?

Q10

Which of the following breast cancers is most often bilateral ?

Molecular Basis of Disease Indian Medical PG Practice Questions and MCQs

Question 1: Sumoylation of histone proteins is associated with

A. Activation of gene transcription
B. Condensation of chromosome
C. Transcription repression (Correct Answer)
D. DNA replication

Explanation: ***Transcription repression*** - **Sumoylation** is a post-translational modification involving the covalent attachment of **Small Ubiquitin-like Modifier (SUMO) proteins** to target proteins, which leads to transcriptional repression. - When histones are sumoylated, it alters chromatin structure and recruits **transcriptional corepressors**, making the DNA less accessible for transcription factors. - This is the **primary and well-established function** of histone sumoylation in gene regulation. *Activation of gene transcription* - **Histone acetylation** and specific methylation patterns (e.g., H3K4me3, H3K36me3) are associated with **transcriptional activation**, not sumoylation. - Sumoylation typically creates a repressive chromatin environment, hindering gene expression. *Condensation of chromosome* - While sumoylation can influence chromatin structure, **chromosome condensation** during cell division is primarily regulated by **condensins** and **cohesins**. - Sumoylation's role in condensation is indirect and not its primary function. *DNA replication* - DNA replication is a separate process from transcriptional regulation and involves DNA polymerases and replication machinery. - Histone sumoylation specifically affects **gene transcription**, not DNA replication.

Question 2: Mutations are due to changes in:

A. DNA nucleotide sequence (Correct Answer)
B. RNA nucleotide sequence
C. Amino acid sequence of ribonuclease
D. Cell membrane

Explanation: ***DNA nucleotide sequence*** - **Mutations** are defined as changes in the **genetic material**, which is primarily composed of **DNA**. - These changes in the **nucleotide sequence** of DNA can alter the genetic code, leading to changes in **protein structure and function**. *RNA nucleotide sequence* - While RNA can have its nucleotide sequence altered, these changes are generally not considered true **mutations** in the heritable sense for most organisms. - RNA is typically a temporary molecule, and changes to its sequence are usually not passed down to subsequent generations. *Amino acid sequence of ribonuclease* - An altered **amino acid sequence** in a protein like ribonuclease is a consequence of a **mutation in the DNA**, not the mutation itself. - **Ribonucleases** are enzymes that catalyze the degradation of RNA, and their structure is determined by the **DNA sequence**. *Cell membrane* - The cell membrane is a **lipid bilayer** with embedded proteins that regulates cellular transport and communication. - While its components can be affected by genetic mutations, alterations in the cell membrane itself do not constitute the primary definition of a **mutation**.

Question 3: An affected male does not have affected children but an affected female always has affected children. Type of inheritance?

A. Autosomal recessive
B. Mitochondrial (Correct Answer)
C. X linked recessive
D. X linked dominant

Explanation: ***Correct Option: Mitochondrial*** - This pattern describes **mitochondrial inheritance**, where all children of an **affected mother** inherit the condition because mitochondria are exclusively inherited from the ovum (maternal inheritance). - An **affected father** cannot pass on the condition to his children, as sperm contribute only nuclear DNA and essentially no mitochondria. - This is the **only inheritance pattern** where an affected male has no affected children while an affected female has all children affected. *Incorrect Option: Autosomal recessive* - This pattern would typically show affected individuals having unaffected parents (who are carriers) and both males and females being affected in equal proportions. - It does not explain the complete absence of transmission from an affected father or universal transmission from an affected mother. - An affected individual could have unaffected children if their partner is not a carrier. *Incorrect Option: X linked recessive* - In **X-linked recessive inheritance**, affected males cannot pass the trait to their sons, but all their daughters would be carriers (not affected). - An affected mother would pass the trait to all her sons (affected) and make all her daughters carriers (not affected), which does not match the described pattern of all children being affected. *Incorrect Option: X linked dominant* - In **X-linked dominant inheritance**, an affected father passes the trait to all his daughters but none of his sons (contradicts "no affected children"). - An affected mother has a 50% chance of passing the trait to **each child**, which is inconsistent with all children of an affected female being affected.

Question 4: Differential expression of the same gene depending on parent of origin is referred to as

A. Mosaicism
B. Nonpenetrance
C. Anticipation
D. Genomic imprinting (Correct Answer)

Explanation: ***Genomic imprinting*** - This phenomenon describes the differential expression of a gene based on its **parent of origin**, meaning that the gene is expressed only from the allele inherited from a specific parent (either maternal or paternal). - This differential expression occurs without altering the underlying DNA sequence and is often mediated by **epigenetic mechanisms** such as DNA methylation. *Mosaicism* - This refers to the presence of **two or more populations of cells** with different genotypes within a single individual who has developed from a single fertilized egg. - It does not involve differential expression of the same gene based on parental origin, but rather **genetic differences arising after fertilization**. *Nonpenetrance* - **Nonpenetrance** describes a situation where an individual carries a disease-causing gene mutation but **does not express the associated phenotype** or clinical symptoms. - This concept explains variability in disease manifestation, not differential gene expression based on parental origin. *Anticipation* - **Anticipation** is a phenomenon in genetic disorders where the symptoms become **more severe** and/or appear at an **earlier age** in successive generations. - This is often seen in disorders caused by expansion of trinucleotide repeats, such as Huntington's disease, and is not related to parent-of-origin gene expression.

Question 5: Which of the following is a primarily RNA based technique?

A. Western blotting
B. Northern blotting (Correct Answer)
C. Southern blotting
D. Sanger's technique

Explanation: ***Northern blotting*** - **Northern blotting** is a molecular biology technique used to study **gene expression** by detecting specific **RNA molecules** (mRNA) in a sample. - It involves separating RNA fragments by **gel electrophoresis**, transferring them to a membrane, and then detecting specific sequences using **labeled probes**. *Western blotting* - **Western blotting** is a technique used to detect specific **proteins** in a sample. - It involves separating proteins by **gel electrophoresis**, transferring them to a membrane, and then detecting specific proteins using labeled **antibodies**. *Southern blotting* - **Southern blotting** is a molecular biology method used for the detection of **specific DNA sequences** in DNA samples. - It involves separating **DNA fragments** by **gel electrophoresis**, transferring them to a membrane, and then hybridizing with a labeled probe. *Sanger's technique* - **Sanger sequencing**, or the **dideoxy chain-termination method**, is a widely used method for **DNA sequencing**. - It uses **dideoxynucleotides** to terminate DNA synthesis at specific bases, allowing the determination of the **DNA sequence**.

Question 6: In which type of lung carcinoma is the p53 mutation most commonly observed?

A. Adenocarcinoma
B. Squamous cell carcinoma (SCC) (Correct Answer)
C. Large cell carcinoma
D. Small cell carcinoma

Explanation: ***Small cell carcinoma*** - **Small cell lung carcinoma (SCLC)** has the highest frequency of **p53 mutations**, occurring in approximately **90-95%** of cases. - These mutations are associated with the **aggressive nature** and **poor prognosis** of SCLC, contributing to its rapid growth and early metastasis. *Adenocarcinoma* - **Adenocarcinoma** has p53 mutations in approximately **50-60%** of cases, which is less frequent than SCLC. - This subtype is more commonly associated with **EGFR mutations** and **ALK rearrangements**, particularly in non-smokers. *Squamous cell carcinoma (SCC)* - **Squamous cell carcinoma** shows p53 mutations in about **70-80%** of cases, but still lower than SCLC. - It is more strongly associated with **smoking** and often displays mutations in **CDKN2A** and **PIK3CA** pathways. *Large cell carcinoma* - **Large cell carcinoma** has variable p53 mutation rates, typically **40-60%** of cases. - This subtype is less well-characterized molecularly and represents a **diagnosis of exclusion** among lung cancers.

Question 7: Which one of the following is an autosomal dominant disorder?

A. Cystic fibrosis
B. Hereditary spherocytosis (Correct Answer)
C. Sickle cell anemia
D. G-6PD deficiency

Explanation: ***Hereditary spherocytosis*** - It is characterized by **autosomal dominant inheritance** [1], leading to the destruction of red blood cells. - Mutations in proteins that maintain the **red blood cell membrane** integrity result in spherocyte formation [1]. *Cystic fibrosis* - This condition follows a **autosomal recessive inheritance pattern**, requiring two copies of the mutated gene for disease manifestation. - It is caused by mutations in the **CFTR gene**, affecting chloride transport and leading to thick secretions. *G-6PD deficiency* - This disorder is inherited in an **X-linked recessive manner** [2], primarily affecting males and transmitted through carrier females. - Characterized by **hemolytic anemia** triggered by certain medications or infections, it does not follow dominant inheritance [2]. *Sickle cell anemia* - Sickle cell anemia is also an **autosomal recessive disorder** [3], meaning affected individuals must inherit two copies of the sickle cell gene. - It results in a mutation in the **HBB gene**, leading to the production of abnormal hemoglobin (HbS) [3].

Question 8: An electron microscopy of muscle biopsy shows 'parking lot' appearance. Which additional finding would confirm myotonic dystrophy?

A. Ragged red fibers
B. Ring fibers (Correct Answer)
C. Central cores
D. Nemaline rods

Explanation: ***Ring fibers*** - **Ring fibers** are a classic histopathological feature seen in **myotonic dystrophy**, characterized by peripheral myofibrils arranged circularly around a central core [1]. - The "parking lot" appearance on electron microscopy refers to collections of **sarcoplasmic reticulum** and **T-tubules**, which can be seen in various myopathies but are often prominent in myotonic dystrophy, complementing the presence of ring fibers [1]. *Ragged red fibers* - **Ragged red fibers** are characteristic of **mitochondrial myopathies**, indicating abnormal proliferation of mitochondria beneath the sarcolemma. - They are typically identified with **Gomori trichrome stain** and are not a feature of myotonic dystrophy. *Central cores* - **Central cores** are a hallmark of **central core disease**, a congenital myopathy, and are regions within muscle fibers where oxidative enzyme activity is absent. - These are not typically associated with myotonic dystrophy; rather, they suggest a different underlying genetic defect affecting muscle structure. *Nemaline rods* - **Nemaline rods** are rod-like inclusions observed in muscle fibers in **nemaline myopathy**, an inherited disorder often associated with mutations in genes encoding components of the thin filament. - They are distinct from the pathological findings in myotonic dystrophy and point to a specific type of congenital myopathy. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 732-733.

Question 9: BCR-ABL fusion gene is MOST CHARACTERISTICALLY seen in?

A. CML (Correct Answer)
B. AML
C. Chronic Lymphocytic Leukemia (CLL)
D. Acute Lymphoblastic Leukemia (ALL)

Explanation: ***CML*** - The **BCR-ABL gene mutation** is characteristic of **Chronic Myeloid Leukemia (CML)**, resulting from a translocation between chromosomes 9 and 22 [1]. - This mutation leads to the production of the **BCR-ABL fusion protein**, which promotes cell proliferation and inhibits apoptosis [1]. *AML* - Acute Myeloid Leukemia (AML) does not typically exhibit the **BCR-ABL fusion gene**; rather, it is associated with various other genetic mutations. - Key features of AML include **myeloblast proliferation** and it presents with different cytogenetic abnormalities like **FLT3 or NPM1 mutations**. *CLL* - Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of **mature lymphocytes**, not the **BCR-ABL mutation**. - It is often associated with mutations such as **TP53** and **NOTCH1**, distinct from myeloid malignancies. *ALL* - Acute Lymphoblastic Leukemia (ALL) is primarily linked with **chromosomal translocations** involving **the TCF3** gene or others, but not specifically with **BCR-ABL**. - In ALL, **lymphoid progenitor cells** proliferate, whereas CML is primarily a **myeloid process** associated with the BCR-ABL gene [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 624-625.

Question 10: Which of the following breast cancers is most often bilateral ?

A. Lobular carcinoma of the breast (Correct Answer)
B. Medullary carcinoma of the breast
C. Ductal carcinoma of the breast
D. Colloid carcinoma of the breast

Explanation: ***Lobular carcinoma of the breast*** - **Invasive lobular carcinoma (ILC)** is the breast cancer subtype most frequently associated with **bilateral disease**, occurring in 5% to 28% of cases. [1] - This higher rate of bilaterality is partly due to the diffuse growth pattern of lobular carcinoma, which can make it more challenging to detect and may lead to synchronous or metachronous involvement of both breasts. [1] *Medullary carcinoma of the breast* - **Medullary carcinoma** is a rare and often well-circumscribed type of breast cancer that typically presents as a solitary mass and is not characteristically bilateral. [1] - It has a generally better prognosis than other invasive ductal carcinomas and is often associated with a BRCA1 mutation. [1] *Ductal carcinoma of the breast* - **Invasive ductal carcinoma (IDC)**, also known as no special type (NST), is the most common form of breast cancer, but it is less frequently bilateral than lobular carcinoma. [1] - While bilateral IDC can occur, it is a less defining characteristic compared to ILC. *Colloid carcinoma of the breast* - **Colloid (mucinous) carcinoma** is a distinct and relatively rare subtype of invasive ductal carcinoma, characterized by tumor cells floating in pools of mucin. - It usually presents as a solitary mass and is not known for a higher incidence of bilaterality. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 454-456.

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