Epigenetics and Disease — MCQs
Sumoylation of histone proteins is associated with
Deamination of methylated cytosine forms which of the following?
Which of the following best defines genomic imprinting?
DNA Methylation is not related to?
Secondary leukemias are caused by
Which of the following statements about gene therapy is false?
Identify the gene commonly involved in the condition shown in the image?
Which of the following conditions is characterized by the presence of telangiectasia?
Gluten sensitive enteropathy is strongly associated with:-
Which one of the following is an autosomal recessive disease?
Epigenetics and 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: Deamination of methylated cytosine forms which of the following?
- A. Uracil
- B. Thymine (Correct Answer)
- C. Cytosine
- D. Guanine
Explanation: ***Thymine*** - Deamination of **5-methylcytosine** removes the amine group at the 4-position and replaces it with a keto group, forming **thymine**. - This reaction can lead to a common type of point mutation, as the DNA repair machinery might fail to distinguish this naturally occurring base from normal thymine. *Uracil* - **Uracil** is formed by the deamination of **unmethylated cytosine**, not methylated cytosine. - Uracil is a base found in RNA but not typically in DNA, so its presence in DNA signals a repair event. *Cytosine* - **Cytosine** is the original base before deamination occurs; deamination is a chemical modification that changes cytosine into another base. - If a base remains cytosine, it means deamination has not taken place. *Guanine* - **Guanine** is a purine base and is structurally unrelated to cytosine or its deamination products. - Deamination primarily affects pyrimidine bases like cytosine and uracil, not purines like guanine.
Question 3: Which of the following best defines genomic imprinting?
- A. Different expression of a gene depending on the parent of origin. (Correct Answer)
- B. Expression of genes silenced on one chromosome through random X-inactivation.
- C. Parent-specific gene expression due to chromosomal deletions only.
- D. Uniparental disomy is a condition where both alleles come from one parent.
Explanation: ***Different expression of gene depending on parent of origin*** - Genomic imprinting refers to the phenomenon where genes are expressed in a parent-of-origin-specific manner, affecting gene expression based on whether the allele is inherited from the mother or father [1]. - This can lead to different phenotypic outcomes and is critical in various genetic disorders [1]. *Angelman syndrome is due to maternal deletion of chromosome 15* - Angelman syndrome is caused by a **paternal deletion** of chromosome 15 and maternal disomy, not a deletion from the mother [1]. - The maternal genes on this chromosome are typically imprinted and thus not expressed in the absence of the paternal contribution [1]. *Prader-Willi syndrome is paternal deletion of chromosome 15* - Prader-Willi syndrome is actually a result of a **maternal deletion** or paternal imprinting of chromosome 15, leading to loss of function of paternal genes . - The absence of these paternal genes causes the manifestations of the syndrome, making this statement incorrect . *Uniparental disomy is a condition where both alleles come from one parent, not genomic imprinting* - While uniparental disomy involves both alleles coming from one parent, it does **not directly relate to** genomic imprinting, which modulates the expression based on the parental origin [1]. - Uniparental disomy can lead to imprinting disorders only if the involved genes are subject to genomic imprinting [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 181-183.
Question 4: DNA Methylation is not related to?
- A. DNA Replication
- B. Gene silencing
- C. Capping (Correct Answer)
- D. Mismatch repair
Explanation: ***Capping*** - **Capping** is a modification of messenger RNA (mRNA) that occurs during **mRNA processing** in eukaryotes, involving the addition of a 7-methylguanosine cap to the 5' end of the mRNA molecule. - This process is crucial for mRNA stability, translation initiation, and nuclear export, and is entirely **independent of DNA modifications** like DNA methylation. *DNA Replication* - DNA methylation plays a role in **DNA replication** to distinguish newly synthesized strands from parental strands during **DNA repair**. - In bacteria, methylation at specific sites (**Dam methylase**) helps in **mismatch repair** by identifying the parental strand. *Gene silencing* - **DNA methylation** of CpG islands in promoter regions is a well-established mechanism for **gene silencing** by altering chromatin structure and preventing transcription factor binding. - This epigenetic modification leads to stable transcriptional repression and is critical for processes like X-chromosome inactivation and genomic imprinting. *Mismatch repair* - In prokaryotes, **DNA methylation** marks the parental strand, which is used by the **mismatch repair system** to correct errors on the newly synthesized, unmethylated strand. - In eukaryotes, while not directly marking strands, DNA methylation can influence the efficiency of mismatch repair pathways by altering chromatin accessibility.
Question 5: Secondary leukemias are caused by
- A. Antimetabolites
- B. Vinca alkaloids
- C. Actinomycin D
- D. Alkylating agents (Correct Answer)
Explanation: ***Alkylating agents*** - **Alkylating agents**, such as **cyclophosphamide**, **chlorambucil**, **melphalan**, and **busulfan**, are highly associated with the development of secondary leukemias, particularly **acute myeloid leukemia (AML)** and **myelodysplastic syndrome (MDS)**. - They cause **DNA damage** by forming covalent bonds with DNA, leading to mutations and chromosomal aberrations (especially deletions of chromosomes 5 and 7) that can promote leukemogenesis. - The latency period is typically **5-7 years** after exposure, and the risk is dose-dependent. *Antimetabolites* - **Antimetabolites**, like **methotrexate** and **5-fluorouracil**, interfere with **DNA replication** and repair but are less frequently linked to secondary leukemias compared to alkylating agents. - While they can cause bone marrow suppression, their mechanism of action typically involves disrupting nucleotide synthesis rather than directly inducing the specific chromosomal changes seen in secondary leukemias. *Vinca alkaloids* - **Vinca alkaloids**, such as **vincristine** and **vinblastine**, primarily target **microtubule formation** and inhibit cell division, often used in cancer chemotherapy. - They are not a significant cause of secondary leukemias; instead, they primarily cause **neurotoxicity** and bone marrow suppression as side effects. *Actinomycin D* - **Actinomycin D** (dactinomycin) acts by intercalating into **DNA** and inhibiting RNA synthesis, making it an **antitumor antibiotic**. - While it is a potent chemotherapy agent with various side effects, it is not a primary cause of **secondary leukemias**, which are predominantly associated with alkylating agents and topoisomerase II inhibitors.
Question 6: 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 7: Identify the gene commonly involved in the condition shown in the image?
- A. RAS
- B. RET
- C. BRAF V600E (Correct Answer)
- D. P53
Explanation: ***BRAF V600E*** - The image displays cells with **Langerhans cell morphology**, including folded nuclei and abundant pale cytoplasm, which are characteristic of **Langerhans cell histiocytosis (LCH)** [1]. - The **BRAF V600E mutation** is the most common genetic alteration found in LCH, present in about 50-60% of cases and activating the MAPK pathway [1]. *RAS* - **RAS mutations** are frequently seen in various cancers, including colorectal adenocarcinoma, pancreatic adenocarcinoma, and non-small cell lung cancer. - While RAS pathway activation can occur in LCH, a direct RAS mutation is not the most common genetic driver; rather, downstream effectors like BRAF V600E are more prominent [1]. *RET* - **RET mutations** are primarily associated with **medullary thyroid carcinoma** (in both sporadic and inherited forms like MEN 2A and MEN 2B) and can also be found in certain types of lung cancer. - They are not a characteristic genetic alteration for Langerhans cell histiocytosis. *P53* - The **TP53 gene** encodes the tumor suppressor protein p53, and mutations in this gene are among the most frequent genetic alterations across a wide spectrum of human cancers. - Although p53 plays a critical role in cell cycle regulation and apoptosis, it is not a primary or common driver mutation specifically associated with Langerhans cell histiocytosis [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. 629-630.
Question 8: Which of the following conditions is characterized by the presence of telangiectasia?
- A. Hereditary hemorrhagic telangiectasia (Correct Answer)
- B. Telangiectasia due to systemic sclerosis
- C. Telangiectasia due to rosacea
- D. Acquired telangiectasia due to sun exposure
Explanation: ***Hereditary hemorrhagic telangiectasia*** - This condition, also known as **Osler-Weber-Rendu disease**, is a **genetic disorder** resulting in abnormal blood vessel formation, leading to **telangiectasias** and arteriovenous malformations that can cause significant bleeding. - Key diagnostic criteria include spontaneous recurrent nosebleeds, multiple mucocutaneous telangiectasias, visceral organ involvement (e.g., pulmonary, hepatic, cerebral AVMs), and a family history. *Telangiectasia due to systemic sclerosis* - While telangiectasias can be a feature of **systemic sclerosis** (especially the limited cutaneous form, **CREST syndrome**), they are typically localized and are not the primary defining characteristic of the disease. - Systemic sclerosis is primarily characterized by **fibrosis of skin and internal organs**, and the telangiectasias are a secondary manifestation, not the fundamental underpinning of the condition as in HHT. *Telangiectasia due to rosacea* - **Rosacea** is a chronic inflammatory skin condition characterized by facial erythema, papules, pustules, and **telangiectasias**, particularly on the cheeks and nose. - However, rosacea-associated telangiectasias are localized to the face and are part of a broader inflammatory dermatological process, distinct from the systemic vascular abnormalities seen in HHT. *Acquired telangiectasia due to sun exposure* - **Sun exposure** can indeed cause **telangiectasias**, particularly on sun-damaged skin, due to chronic photodamage to dermal blood vessels. - These are generally localized, non-syndromic, and a result of environmental factors rather than a systemic or inherited disorder as seen in hereditary hemorrhagic telangiectasia.
Question 9: Gluten sensitive enteropathy is strongly associated with:-
- A. HLA-DQ2 (Correct Answer)
- B. HLA-DQ3
- C. Blood group B
- D. HLA-DR4
Explanation: ### HLA-DQ2 - **HLA-DQ2** is the most significant **genetic risk factor** for **celiac disease** (gluten-sensitive enteropathy), present in about 90-95% of patients [1]. - Its presence is necessary, though not sufficient, for the development of the disease, playing a crucial role in immune response to **gluten peptides** [1]. ### HLA-DQ3 - While other HLA-DQ alleles exist, **HLA-DQ3** is not primarily associated with celiac disease. - The dominant susceptibility alleles are **HLA-DQ2** and, to a lesser extent, **HLA-DQ8** [1]. ### Blood group B - There is **no established strong association** between **blood group B** and the development of celiac disease. - Blood groups are primarily related to red blood cell antigens, not directly to autoimmune conditions like celiac disease. ### HLA-DR4 - **HLA-DR4** is mainly associated with other autoimmune diseases, particularly **rheumatoid arthritis**, and is not a primary genetic marker for celiac disease. - Although it's part of the MHC class II locus, its specific alleles like **HLA-DQ2** and **HLA-DQ8** are more relevant for celiac disease [1].
Question 10: Which one of the following is an autosomal recessive disease?
- A. Retinitis pigmentosa
- B. Vitamin D resistant rickets
- C. Cystic fibrosis (Correct Answer)
- D. Neurofibromatosis
Explanation: ***Cystic fibrosis*** - **Cystic fibrosis** is caused by mutations in the **CFTR gene**, leading to defective chloride transport and thick, sticky mucus. - It is inherited in an **autosomal recessive pattern**, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the disease. *Retinitis pigmentosa* - **Retinitis pigmentosa** is a group of inherited eye disorders, and while some forms are X-linked or autosomal dominant, a significant portion are also inherited in an **autosomal recessive pattern**. - However, it's not exclusively autosomal recessive, making cystic fibrosis a more definitive answer in this context. *Vitamin D resistant rickets* - **Vitamin D resistant rickets**, also known as **X-linked hypophosphatemic rickets**, is primarily inherited in an **X-linked dominant pattern**. - It is characterized by impaired renal phosphate reabsorption and skeletal abnormalities despite normal vitamin D levels. *Neurofibromatosis* - **Neurofibromatosis type 1 (NF1)** and **Neurofibromatosis type 2 (NF2)** are both inherited in an **autosomal dominant pattern**. - NF1 is characterized by **café-au-lait spots**, **neurofibromas**, and optical gliomas, while NF2 involves **bilateral vestibular schwannomas**.
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