MCQ Quiz-DNA Methylation and Imprinting

MCQ Quiz: DNA Methylation and Genomic Imprinting

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DNA methylation is a fundamental epigenetic mechanism that plays a crucial role in regulating gene expression, cellular differentiation, and genomic stability. Genomic imprinting, a direct consequence of this process, results in parent-of-origin-specific gene expression that is vital for normal development. For PharmD students, understanding these principles is key to grasping the epigenetic basis of diseases like cancer and the mechanisms of emerging epigenetic drugs. This quiz will test your knowledge of the enzymes, processes, and clinical relevance of DNA methylation and imprinting.

1. DNA methylation is a key epigenetic modification that involves the addition of a methyl group to which nucleotide base?

  • Adenine
  • Guanine
  • Thymine
  • Cytosine

Answer: Cytosine

2. In mammals, DNA methylation occurs almost exclusively in the context of a:

  • Poly(A) tail
  • CpG dinucleotide
  • TATA box
  • Start codon

Answer: CpG dinucleotide

3. The enzymes responsible for establishing new DNA methylation patterns, often during development, are called:

  • Maintenance methyltransferases.
  • De novo methyltransferases (DNMT3a and DNMT3b).
  • Histone deacetylases (HDACs).
  • DNA polymerases.

Answer: De novo methyltransferases (DNMT3a and DNMT3b).

4. The enzyme responsible for copying the existing methylation pattern to the new DNA strand during replication is a:

  • De novo methyltransferase (DNMT3a).
  • Maintenance methyltransferase (DNMT1).
  • Histone acetyltransferase (HAT).
  • Topoisomerase.

Answer: Maintenance methyltransferase (DNMT1).

5. Increased DNA methylation in the promoter region of a gene is typically associated with:

  • Active transcription.
  • Transcriptional silencing or repression.
  • The initiation of DNA replication.
  • The formation of euchromatin.

Answer: Transcriptional silencing or repression.

6. “Genomic imprinting” is an epigenetic phenomenon that results in:

  • The expression of both alleles of a gene equally.
  • The mutation of one allele of a gene.
  • Gene expression that occurs in a parent-of-origin-specific manner (i.e., only the maternal or paternal allele is expressed).
  • The silencing of all genes on one chromosome.

Answer: Gene expression that occurs in a parent-of-origin-specific manner (i.e., only the maternal or paternal allele is expressed).

7. The molecular mechanism underlying genomic imprinting is the:

  • Differential DNA methylation of imprinting control regions (ICRs).
  • A change in the DNA sequence of one allele.
  • The process of X-chromosome inactivation.
  • The action of RNA polymerase.

Answer: Differential DNA methylation of imprinting control regions (ICRs).

8. Prader-Willi syndrome and Angelman syndrome are classic examples of diseases caused by:

  • Aneuploidy (an incorrect number of chromosomes).
  • Defects in genomic imprinting on chromosome 15.
  • A single nucleotide polymorphism.
  • A viral infection.

Answer: Defects in genomic imprinting on chromosome 15.

9. How does DNA methylation inhibit transcription?

  • It can physically block the binding of transcription factors to the DNA.
  • Methylated DNA can recruit proteins that promote a condensed, repressive chromatin structure.
  • It can signal for the removal of activating histone marks.
  • All of the above.

Answer: All of the above.

10. “CpG islands” are regions of the genome that have a high frequency of CpG sites. In actively transcribed “housekeeping” genes, these islands are typically:

  • Heavily methylated.
  • Unmethylated.
  • Deleted from the genome.
  • Bound by repressor proteins.

Answer: Unmethylated.

11. The process of imprinting is established in the ________ and is generally maintained throughout the somatic cells of an individual’s life.

  • Germline (sperm and egg cells)
  • Liver cells
  • Neurons
  • Skin cells

Answer: Germline (sperm and egg cells)

12. The chemotherapeutic agent azacitidine is a hypomethylating agent that works by inhibiting:

  • Histone deacetylases (HDACs).
  • DNA methyltransferases (DNMTs).
  • DNA polymerase.
  • Topoisomerase.

Answer: DNA methyltransferases (DNMTs).

13. A key principle behind using a DNMT inhibitor in cancer therapy is to:

  • Cause widespread gene silencing.
  • Induce DNA mutations.
  • Reactivate the expression of silenced tumor suppressor genes.
  • Promote the growth of cancer cells.

Answer: Reactivate the expression of silenced tumor suppressor genes.

14. Which of the following statements about genomic imprinting is TRUE?

  • Imprinted genes are expressed from both the maternal and paternal alleles.
  • Imprinting patterns are established after birth.
  • Imprinting is an example of epigenetic inheritance.
  • All genes in the human genome are imprinted.

Answer: Imprinting is an example of epigenetic inheritance.

15. A “health disparity” could arise if a new, expensive epigenetic drug that targets DNA methylation is:

  • Made accessible to all populations.
  • So expensive that it is only available to the wealthiest patients.
  • Covered by government insurance programs.
  • Easy to administer.

Answer: So expensive that it is only available to the wealthiest patients.

16. The “forging ahead” mindset in pharmacy means embracing personalized medicine, which may one day use a patient’s __________ profile to guide cancer therapy.

  • Tumor DNA methylation
  • Blood type
  • Cholesterol
  • Age

Answer: Tumor DNA methylation

17. The molecular biology technique of “bisulfite sequencing” is used to:

  • Amplify a segment of DNA.
  • Determine the specific pattern of DNA methylation across a region of DNA.
  • Separate proteins by size.
  • Clone a gene into a plasmid.

Answer: Determine the specific pattern of DNA methylation across a region of DNA.

18. A key part of the “Introduction to Pharmacy Informatics” is understanding that an EHR of the future will need to:

  • Store and interpret complex epigenetic data like DNA methylation patterns.
  • Only store a patient’s demographic information.
  • Be based on a paper-chart system.
  • Limit a pharmacist’s access to data.

Answer: Store and interpret complex epigenetic data like DNA methylation patterns.

19. A pharmacist’s knowledge of “DNA structure” is the foundation for understanding how:

  • The methyl group is added to the 5-carbon of the cytosine ring.
  • Methylation in the major groove can block protein binding.
  • The DNA backbone is negatively charged.
  • All of the above.

Answer: All of the above.

20. The “regulation” of new drugs that target epigenetic mechanisms like DNA methylation is the responsibility of the:

  • DEA
  • FDA
  • CMS
  • EPA

Answer: The FDA

21. A common epigenetic alteration in many cancers is the global _________ of the genome and the focal _________ of CpG islands in tumor suppressor genes.

  • Hypomethylation; hypermethylation
  • Hypermethylation; hypomethylation
  • Acetylation; deacetylation
  • Deacetylation; acetylation

Answer: Hypomethylation; hypermethylation

22. A “business plan” for a biotech company developing a new DNMT inhibitor would need to heavily feature:

  • The science of DNA methylation and its role in cancer.
  • A strong intellectual property (patent) position.
  • A clear clinical development plan.
  • All of the above.

Answer: All of the above.

23. The “leadership” skill of staying current with scientific advances is critical for a pharmacist because:

  • The field of epigenetics and its therapeutic applications are rapidly evolving.
  • The principles of pharmacy have not changed in a century.
  • It is not a required skill.
  • It only helps with passing exams.

Answer: The field is rapidly evolving with new discoveries and drug targets.

24. The enzymes that “read” DNA methylation marks and recruit other proteins to silence genes are known as:

  • Histone acetyltransferases (HATs).
  • Methyl-CpG-binding domain proteins (MBDs).
  • DNA ligases.
  • RNA polymerases.

Answer: Methyl-CpG-binding domain proteins (MBDs).

25. A key “policy” debate surrounding epigenetics is:

  • The ethics of using epigenetic information for insurance or employment purposes.
  • The price of over-the-counter medications.
  • The regulation of pharmacy technicians.
  • The schedule of controlled substances.

Answer: The ethics of using epigenetic information for insurance or employment purposes.

26. The “human resources” department of a cancer research institute would need to recruit scientists with expertise in:

  • Epigenetics and DNA methylation.
  • Marketing.
  • Finance.
  • Only human relations.

Answer: Epigenetics and DNA methylation.

27. An “analytics and reporting system” could be used in research to:

  • Analyze whole-genome methylation data from thousands of patients to find new biomarkers for disease.
  • Track pharmacy inventory.
  • Schedule patient appointments.
  • Create a marketing brochure.

Answer: Analyze whole-genome methylation data from thousands of patients to find new biomarkers for disease.

28. A key principle of “eukaryotic transcription” is its regulation by:

  • The sigma factor.
  • The coupling of transcription and translation.
  • Epigenetic mechanisms like DNA methylation that control access to promoters.
  • The lac operon.

Answer: Epigenetic mechanisms like DNA methylation that control access to promoters.

29. A “Clinical Decision Support” system could be designed to:

  • Alert a physician to a patient’s known methylation status in a tumor suppressor gene when prescribing a relevant chemotherapy.
  • Dispense a medication.
  • Bill for a hospital stay.
  • It cannot use this type of data.

Answer: Alert a physician to a patient’s known methylation status in a tumor suppressor gene when prescribing a relevant chemotherapy.

30. The ultimate reason pharmacists must understand DNA methylation and imprinting is that these processes are:

  • Fundamental to gene regulation and are increasingly important as therapeutic targets and biomarkers in personalized medicine.
  • An interesting but clinically irrelevant area of science.
  • Only important for genetic counselors.
  • Too complex to ever be applied in a clinical setting.

Answer: Fundamental to gene regulation and are increasingly important as therapeutic targets and biomarkers in personalized medicine.

31. The “erasure” of most epigenetic marks, including methylation, occurs during:

  • Every mitotic cell division.
  • Early embryonic development and in the formation of germ cells.
  • The aging process.
  • The transcription of a gene.

Answer: Early embryonic development and in the formation of germ cells.

32. “Loss of imprinting” (LOI) is an epigenetic defect where:

  • The normally silenced allele of an imprinted gene becomes active.
  • The normally active allele of an imprinted gene is silenced.
  • Both alleles of an imprinted gene are expressed.
  • Both A and C can occur and lead to disease.

Answer: Both A and C can occur and lead to disease.

33. The “service” of genetic counseling is critical for a family affected by an imprinting disorder to:

  • Explain the complex inheritance patterns and recurrence risks.
  • Prescribe medications.
  • Perform the genetic testing.
  • Bill for the procedure.

Answer: Explain the complex inheritance patterns and recurrence risks.

34. The “financials” of developing a drug that targets DNA methylation are:

  • Low-risk and low-cost.
  • High-risk and high-cost.
  • Guaranteed to be profitable.
  • Simple and straightforward.

Answer: High-risk and high-cost.

35. A “negotiation” with a payer for a new, expensive drug that targets DNMTs would require a strong case based on:

  • Evidence of improved clinical outcomes.
  • The drug’s high price.
  • The novelty of its mechanism alone.
  • The personal preference of the oncologist.

Answer: Evidence of improved clinical outcomes.

36. A key part of the “Introduction to the Profession” involves understanding the pharmacist’s role as a lifelong learner, which is essential for keeping up with fields like:

  • Epigenetics.
  • Pharmacy history.
  • Basic chemistry.
  • All of the above.

Answer: All of the above.

37. The “enzymes of DNA metabolism” like DNMT1 are crucial for the _________ of epigenetic states.

  • Inheritance
  • Creation
  • Erasure
  • Reading

Answer: Inheritance

38. The “molecular biology technique” of ChIP-Seq can be used to study DNA methylation indirectly by:

  • Identifying where methyl-CpG-binding proteins are located on the genome.
  • Sequencing the DNA directly.
  • Amplifying the DNA.
  • Separating proteins by size.

Answer: Identifying where methyl-CpG-binding proteins are located on the genome.

39. A pharmacist’s knowledge of “chemotherapeutics” is expanding to include:

  • Drugs that target the epigenetic machinery, like DNMT and HDAC inhibitors.
  • Only traditional cytotoxic agents.
  • Only hormonal therapies.
  • Only targeted therapies.

Answer: Drugs that target the epigenetic machinery, like DNMT and HDAC inhibitors.

40. A “policy” decision to fund large-scale research like the “Epigenome Roadmap” is a function of:

  • Government bodies like the National Institutes of Health (NIH).
  • Private insurance companies.
  • Individual hospitals.
  • Pharmaceutical companies.

Answer: Government bodies like the National Institutes of Health (NIH).

41. The connection between diet and epigenetics suggests that nutrients can:

  • Directly alter the DNA sequence.
  • Influence the availability of methyl groups for DNA methylation.
  • Have no effect on gene expression.
  • Only affect the gut microbiome.

Answer: Influence the availability of methyl groups for DNA methylation.

42. A pharmacist’s “leadership” role in a precision medicine program would involve:

  • Helping to develop protocols for the use of epigenetic biomarkers in clinical practice.
  • Ignoring all new genetic and epigenetic data.
  • Focusing only on the cost of testing.
  • Letting other professions lead all initiatives.

Answer: Helping to develop protocols for the use of epigenetic biomarkers in clinical practice.

43. The “human resources” department in a modern cancer center would need to recruit pharmacists with expertise in:

  • Epigenetics and personalized medicine.
  • Basic dispensing only.
  • Marketing.
  • Finance.

Answer: Epigenetics and personalized medicine.

44. A “health disparity” can be linked to epigenetics, as social and environmental factors like stress and pollution can:

  • Cause lasting, detrimental changes to a person’s epigenome.
  • Have no biological effect.
  • Affect all populations equally.
  • Only be passed down genetically.

Answer: Cause lasting, detrimental changes to a person’s epigenome.

45. The “advocacy” role of a pharmacist might involve:

  • Advocating for insurance coverage of a new epigenetic drug for a patient with a rare cancer.
  • Insisting all patients receive the same treatment.
  • Refusing to counsel a patient on a complex medication.
  • Focusing only on the pharmacy’s profits.

Answer: Advocating for insurance coverage of a new epigenetic drug for a patient with a rare cancer.

46. In which “practice setting” would a pharmacist be most likely to manage patients on epigenetic modifiers?

  • A community pharmacy.
  • A specialized oncology or hematology clinic.
  • A mail-order pharmacy.
  • A supermarket pharmacy.

Answer: A specialized oncology or hematology clinic.

47. An “Electronic Health Record” (EHR) must be designed with the capacity to:

  • Store and interpret complex epigenetic data to be useful for the future of personalized medicine.
  • Only store basic demographic information.
  • Limit the amount of data that can be entered.
  • Be used on paper only.

Answer: Store and interpret complex epigenetic data to be useful for the future of personalized medicine.

48. An “antidote” for a drug that causes epigenetic changes would most likely:

  • Not exist; treatment would be supportive.
  • Be naloxone.
  • Be flumazenil.
  • Be a simple chemical binder.

Answer: Not exist; treatment would be supportive.

49. The “DNA repair mechanisms” are distinct from methylation, but a failure in these systems can lead to mutations in:

  • The DNMT enzymes themselves, causing a global methylation defect.
  • The histone proteins.
  • The RNA polymerase.
  • The ribosomes.

Answer: The DNMT enzymes themselves, causing a global methylation defect.

50. The ultimate principle of why pharmacists study DNA methylation is that it is a key mechanism of _________ that is both fundamental to life and a major new frontier for ________.

  • Gene regulation; pharmacotherapy.
  • DNA replication; surgery.
  • Protein synthesis; marketing.
  • Drug metabolism; billing.

Answer: Gene regulation; pharmacotherapy.

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