FINAL EXAM PRACTICE Q

Question 1

SNP1 and SNP2 has a linkage disequilibrium (LD) R2 value of 0.9. Which of the following is likely to be true:

A.SNP1 and SNP2 are inherited independently of each other

B.SNP1 and SNP2 have a high probability to be inherited together

C.SNP1 and SNP2 have a low probability to be inherited together

D.SNP1 and SNP2 are always inherited together

Answer 1

B.SNP1 and SNP2 have a high probability to be inherited together

Question 2

How many base pairs have been identified in the whole human genome? (2 pts)

A.~30 million

B.~300 million

C.~3 billion

D.~3 million

Answer 2

C.~3 billion

Question 3

A missense mutation leads to ___ (2 pts)

A.gain-of-function

B.protein-truncation

C.loss-of-function

D.either gain-of-function or loss-of-function depending on the exact amino acid change

Answer 3

D.either gain-of-function or loss-of-function depending on the exact amino acid change

Question 4

CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss-of-function allele, CYP2C19*2 (c.G681A; protein coding sequence), is associated with increased risk for serious adverse cardiovascular events in both heterozygous (40% of the population are G/A) and homozygous patients (15% of the population are A/A) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI).

The minor allele frequency of this SNP is about__ (2 pts)

A.15%

B.20%

C.35%

D.45%

Answer 4

C.35%

Question 5

Read the following guideline and answer the following 4 questions:

CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss-of-function allele, CYP2C19*2 (c.G681A; protein coding sequence), is associated with increased risk for serious adverse cardiovascular events in both heterozygous (40% of the population are G/A) and homozygous patients (15% of the population are A/A) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI).

Patients carrying which of following genotypes of the SNP are likely to have the lowest CYP2C19 enzymatic activity? (2 pts).

A.G/G

B.G/A

C.A/A

D.All genotypes will be the same

Answer 5

C.A/A

Question 6

Read the following guideline and answer the following 4 questions:

CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss-of-function allele, CYP2C19*2 (c.G681A; protein coding sequence), is associated with increased risk for serious adverse cardiovascular events in both heterozygous (~40% of the population) and homozygous patients (~15% of the population) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI).

Is the c.G681A SNP located in an exon?

True
False

Answer 6

TRUE

Question 7

Read the following guideline and answer the following 4 questions:

CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss-of-function allele, CYP2C19*2 (c.G681A; protein coding sequence), is associated with increased risk for serious adverse cardiovascular events in both heterozygous (40% of the population are G/A) and homozygous patients (15% of the population are A/A) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI).

In a population of 300 patients, how many people are likely to carry a G/G genotype at this SNP? (2pt)

A.45

B.135

C.165

D.90

Answer 7

B.135

Question 8

Which statement about whole exome/genome sequencing is incorrect? (2 pts)

A.Generates a large amount data

B.Relatively low cost per SNP

C.Can detect almost all kinds of polymorphisms

D.1-3x sequencing coverage is commonly used to identify human SNPs

Answer 8

D.1-3x sequencing coverage is commonly used to identify human SNPs

Question 9

Red blood cells can be used to obtain DNA for PGx testing (2 pts)

True
False

Answer 9

False

Question 10

One patient comes to your pharmacy to get clopidogrel and told you that his doctor ordered a genetic testing from him, which shows his CYP2C19 as *5 and *8. Using PHARMGKB, what advice you will give to the patient? (2 pts)

A.Increase the dose because this patient is an ultrarapid metabolizer

B.Reduce the dose as the patient is an intermediate metabolizer

C.Keep taking the same dose the doctor prescribed

D.Recommend the switch to alternative therapy because the patient is a poor metabolizer.

Answer 10

D.Recommend the switch to alternative therapy because the patient is a poor metabolizer.

Question 11

A PGx test should be submitted to ___ (2 pt)

A.Any lab that is CLIA certified

B.A CLIA lab offering PGx testing

C.Any lab performing PGx research

D.Any lab offering SNP genotyping

Answer 11

B.A CLIA lab offering PGx testing

Question 12

Which method cannot be used to test both known and unknown alleles? (2 pts)

A.DNA chip

B.Sanger sequencing

C.Next generation sequencing

D.all of them

Answer 12

A.DNA chip

Question 13

You ordered whole exome sequencing for your patient with early onset seizures and found a mutation in SCN8A, which encodes the sodium channel Nav1.6. Functional assays show the mutation causes a gain of function phenotype to make the sodium channel Nav1.6 overactive.

Which of the following therapies is the most likely to be beneficial? (2 pts)

A.Adeno associated virus to deliver a healthy copy of SCN8A

B.mRNA vaccination to activate T cells to treat the patient

C.Antisense oligonucleotide

D.Implantation of stem cell derived neuron into the brain of the patient

Answer 13

C.Antisense oligonucleotide

Question 14

In PGx research, p value <0.05 is commonly used to show statistical significance for a large number of SNPs identified in whole exome sequencing? (2 pts)

True
False

Answer 14

FALSE

Question 15

A patient carries homozygous nonsense mutation in an important gene responsible for a key liver function. Which type of medication is most likely to help this patient? (2 pts)

A.Small molecule drug

B.Gene therapy

C.Antisense oligonucleotides

D.Monoclonal antibody

Answer 15

B.Gene therapy

Question 16

The prevalence of a rare allele (18) was low. Below are the statistics for the 2-year cumulative event rates of this allele: bleeding [1/*18 vs. 1/1: 2 vs. 2.3%; odds ratio (OR), 1.23; 95% confidence interval (CI), 0.16-9.45], stent thrombosis (2 vs. 1.1%; OR, 3.98; 95% CI, 2.4-6.6); composite of any death (5.4 vs. 7.1%; OR, 1.37; 95% CI, 0.32-5.73). Which of the following events is significantly associated with the 1/18 genotype? (2 pts)

A.Bleeding

B.Stent thrombosis

C.Composite of any death

D.All of above

E.None of above

Answer 16

B.Stent thrombosis

Question 17

Repatha and Praluent are what type of drug? (2 pts)

Small molecule drug

Small interfering RNA drug

Mimetic peptide drug

Monoclonal antibody drug

Answer 17

Monoclonal antibody drug

Question 18

To do a good experiment and generate robust data, which one is the least important? (2 pts)

Absolute value of the data

Sample size

Negative control

Positive control

Answer 18

Absolute value of the data

Question 19

Which of the following is not needed for making mRNA-based COVID-19 vaccines that are currently in use? (2 pts)

Lipid coating

Chemically modified mRNA

Sequence information of coronavirus spike protein

Coronavirus particles

Answer 19

Coronavirus particles

Question 20

Which statement about antibodies are not correct? (2 pts)

Antibodies can be engineered to delivery drug

Antibodies can block the function of its target protein

Antibodies are produced by T cells

Antibodies can be used to treat cancers

Answer 20

Antibodies are produced by T cells

Question 21

Which of the following LDL-C concentration is more likely to be the test results of a patient with PCSK9 gain-of-function mutation? (2 pts)

105 mg/dL

46 mg/dL

95 mg/dL

282 mg/dL

Answer 21

282 mg/dL

Question 22

You ordered a sequencing of CYP2C9 for your patient. The results show that there is no known mutant allele identified. However, a novel mutation (heterozygous) in CYP2C9 exon 3 was identified.

Do you think if this patient has normal CYP2C9 enzyme function? (2 pts)

I do not know

No

Yes

The test result is wrong

Answer 22

I do not know

Question 23

Which of the following statements is true about the relationship between variants in DPYD and fluoropyrimidine efficacy and/or safety? (2 points)

Gain-of-function variants in DPYD increase fluoropyrimidine metabolism and have been associated with reduced fluoropyrimidine efficacy

Loss-of-function variants in DPYD reduce fluoropyrimidine bioactivation and have been associated with reduced fluoropyrimidine efficacy

Gain-of-function variants in DPYD increase fluoropyrimidine bioactivation and have been associated with increased fluoropyrimidine efficacy

Loss-of-function variants in DPYD reduce fluoropyrimidine metabolism and have been associated with increased adverse events in fluoropyrimidine treated patients

Answer 23

Loss-of-function variants in DPYD reduce fluoropyrimidine metabolism and have been associated with increased adverse events in fluoropyrimidine treated patients

Question 24

Which of the following is(are) barrier(s) to the implementation of pharmacogenomic testing into clinical practice? Select ALL that apply. (2 points)

Slow transition of basic science knowledge into clinical practice

The pace of technology development cannot keep up with clinical practice changes

The US government has not put forth any significant financial efforts toward precision medicine

The traditional clinical practice model

Answer 24

Slow transition of basic science knowledge into clinical practice

The traditional clinical practice model

Question 25

Which of the following innovative clinical trial designs have helped overcome barriers to the development and approval of drugs within precision medicine? Select all that apply. (2 points)

Double blinded, placebo controlled, randomized clinical trial

Basket trial design

Umbrella trial design

Observational cohort design

Answer 25

Basket trial design

Umbrella trial design

Question 26

Indicate if the following sentence is true or false.

The Precision Medicine Initiative has the goal to enhance research, technology, and policies toward the development of individualized treatments. (2 points)

True
False

Answer 26

TRUE

Question 27

Indicate if the following sentence is true or false.

Precision medicine and personalized medicine can both include pharmacogenomics in the practice of medicine. (2 points)

True
False

Answer 27

TRUE

Question 28

Which of the following is (are) the most likely somatic mutation(s) that could cause cancer? Select ALL that apply.

TMPT*3A

UGT1A1 (TA)7TAA

KRAS Missense Mutation

EGFR deletions in exon 21

Answer 28

KRAS Missense Mutation

EGFR deletions in exon 21

Question 29

The laboratory results of a patient with newly diagnosed non-small cell lung cancer have just been reported. The report indicates the following:

(1) EGFR deletions in exon 19

(2) KRAS Missense Mutation in exon 2

Which initial course of therapy would be the best recommendation in this patient? (2 points)

Cetuximab

Crizotinib

Cytotoxic agents

Ceritinib

Answer 29

Cytotoxic agents

Question 30

This enzyme metabolizes numerous anticancer therapies, including docetaxel and many of the tyrosine kinase inhibitors:

CYP2C19

CYP3A4

CYP2B6

CY92D6

Answer 30

CYP3A4

Question 31

Which type of genetic testing provides the most amount of pharmacogenetic information?

A whole genome sequencing run

A Sanger sequencing run

A whole exome sequencing run

A genotyping panel containing 64 variants

Answer 31

A whole genome sequencing run

Question 32

Which of the following best describes the primary intent of the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines? (2 points)

Recommends the utilization of genetic test results to optimize drug therapy

Provides clinicians information on cutting edge pharmacogenetics tests

Serves as a legal document for the drug manufacturer

Recommends in whom pharmacogenetic testing should be conducted

Answer 32

Recommends the utilization of genetic test results to optimize drug therapy

Question 33

A physician who claims to specialize in treating Chronic Lyme Disease requires patients to sign a contract assuring that they will complete a full one-year course of therapy. Which ethical principle would this contract violate?

Justice

Beneficence

Autonomy

Nonmaleficence

Answer 33

Autonomy

Question 34

The conduct of a pharmacogenomic clinical trial in a developing country in a patient population unlikely to be able to afford such tests raises concerns related to which ethical principle? (2 points)

Beneficence

Nonmaleficence

Justice

Autonomy

Answer 34

Justice

Question 35

Which of the following are examples of genes that may impact drug pharmacokinetics? Select ALL that apply. (2 points)

CYP2C9

UGT1A1

VKORC1

TPMT

Answer 35

CYP2C9

UGT1A1

TPMT

Question 36

Based upon the Genetic Information Nondiscrimination Act, a health insurance company can charge different premium rates to patients based upon genetic predisposition identified as a result of genetic testing. (2 points)

True
False

Answer 36

FALSE

Question 37

Which of the following represent drug target genes? Select ALL that apply. (2 points)

VKORC1

ADRB2

UGT1A1

TPMT

Answer 37

VKORC1

ADRB2

Question 38

Which of the following genes encodes a protein responsible for Phase II drug reactions? (2 points)

UGT1A1

CYP1A2

SLCO1B1

MDR1

Answer 38

UGT1A1

Question 39

Which of the following drug properties are most likely due to genetic variations in drug targets? (2 points)

Ethnic differences in response

Bioavailability

Entry into the central nervous system

Area under the plasma concentration time curve

Answer 39

Ethnic differences in response

Question 40

Which one of the following sites for genetic variations may affect drug pharmacodynamics? (2 points)

Drug transporter proteins

Drug target proteins

CYP450 enzymes

Phase II metabolizing enzymes

Answer 40

Drug target proteins

Question 41

Which of the following drug properties are most likely to be affected by single nucleotide polymorphisms in CYP2D6? (2 points)

Toxicity

Delivery

Absorption

Renal clearance

Answer 41

Toxicity

Question 42

A key guiding principle in medical ethics is that health professionals should put the interests of the patient above their own interests or those of the institution for which they work. This principle is known as? (2 points)

Beneficence

Nonmaleficence

Autonomy

Justice

Answer 42

Beneficence

Question 43

CRISPR/Cas9 technology can be used for the treatment of patients in both in vivo and ex vivo gene-editing therapy. (2 points)

True
False

Answer 43

True

Question 44

Which of the following statements is most likely false in regards to a patient with a TMPT3A3C genotype that is being started on mercaptopurine? (2 points)

The optimal starting dose for this patient has not been established.

This patient is at an increased risk for severe toxicity from conventional doses.

This patient’s tumor will have a positive response to mercaptopurine treatment.

This patient will not achieve therapeutically effective thioguanine concentrations.

Answer 44

This patient will not achieve therapeutically effective thioguanine concentrations.

Question 45

Which of the following is (are) known, proposed, or a likely predictor(s) of irinotecan toxicity? Select ALL that apply (2 points)

Poor performance status

Gilbert’s Syndrome

TPMT23A genotype

Age < 50 years old

Answer 45

Poor performance status

Gilbert’s Syndrome

Question 46

A patient with a TPMT3A3C genotype will have a decreased risk of toxicity to azathioprine treatment. (2 points)

True
False

Answer 46

FALSE

Question 47

Which of the following is a CPIC recommendation regarding clopidogrel use in a patient that is a CYP2C19*2 homozygote? (2 points)

There are no CPIC guidelines for clopidogrel usage

Use prasugrel or ticagrelor if no contraindication

Clopidogrel should be effective at the label-recommended dosage and administration

Double the label’s recommended dosage of clopidogrel

Answer 47

Use prasugrel or ticagrelor if no contraindication

Question 48

Which of the following drugs is associated with toxicity that can be at least partially predicted by TPMT genotype (2 points)?

6-mercaptopurine

Allopurinol

Ritonavir

Aripiprazole

Answer 48

6-mercaptopurine

Question 49

Which of the following describes in vivo gene editing approaches used in patients? Select all that apply. (2 points)

Vector carrying a gene editing tool is infused intravenously into the patient and up-taken by the target cells.

Large molecules infused intravenously to patients to suppress an oncogene that is genetically overexpressed in cancer cells.

Cells are separated and genetically modified using CRSPR/Cas9 outside the body then infused to the patient.

Small molecule are administered to patients to suppress an oncogene that is genetically overexpressed in cancer cells.

Answer 49

Vector carrying a gene editing tool is infused intravenously into the patient and up-taken by the target cells.

Question 50

A 55-year-old Caucasian male has been taking 40 mg simvastatin for over one year with no observed reduction in LDL. You would like to adjust his therapy to enhance his LDL response, but he has been found to have a SLCO1B1 521CC genotype (5/5 allele) with no symptoms of myopathy. Which of the following is consistent with the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations to maximize LDL reduction in this patient? (2 Points)

Increase the simvastatin dose to 80 mg and routinely monitor creatinine phosphokinase.

Maintain the simvastatin dose at 40 mg.

Reduce the simvastatin dosage to 10 mg.

Use an alternative drug to achieve LDL target reduction.

Answer 50

Use an alternative drug to achieve LDL target reduction.

Question 51

Which of the following is the best target for chimeric antigen receptor T cells in B cell malignancies? (2 points)

CD19

CAR

Cytokines

CD3

Answer 51

CD19