Pharmacogenomics 1

Question 1

What allele nomenclature provides information on which allele is the wild type?
A. Alpha/numeric
B. Star
C. RS

Answer 1

B. Star

C. RS - this is identification of the variant

Question 2

SNP polymorphisms are the only type that have clinical relevance. T/F

Answer 2

False

Question 3

What does VKORC1 code for?

Answer 3

It is vitamin K oxidative reductase complex 1 and it codes for the warfarin enzyme.

Question 4

What do the first few letters/numbers of the allele numeric/alphabetic nomenclature identify?

Answer 4

The gene

Question 5

What do the numbers of allele Numeric/Alphabetic Nomenclature identify?

Answer 5

They indicate the location of the nucleotide on the gene. ex: 1173

Question 6

What does Allelle Numeric/Alphabetic Nomenclature look like?

Answer 6

VKORC1 1173 T

Question 7

Are you able to tell which allele is the wild type or the variant on Allele Numeric/Alphabetic nomenclature?

Answer 7

No

Question 8

What are the different ways to name a polymorphism?

Answer 8

Allele Numeric/Alphabetic Nomenclature
SNP Nomenclature
Allele Star Nomenclature
Reference SNP Nomenclature (rs)
Genotype Nomenclature
Haplotype Nomenclature

Question 9

What is an example of SNP nomenclature?

Answer 9

VKORC1 1173 C>T

Question 10

What does the C represent in the example of VKORC1 1173 C>T?

Answer 10

The wildtype

Question 11

What does the T represent in the example of VKORC1 1173 C>T?

Answer 11

The change that made the polymorphism

Question 12

What is an example of Allele Star Nomenclature?

Answer 12

CYP2C19 *1 - wildtype

Question 13

What are the different alleles of the CYP2C19 and what is their enzyme activity?

Answer 13

*1 - wild type so has normal activity
*2 - no enzyme activity
3 - no enzyme activity
(2 and *3 stop transcription and therefore result in an short enzyme that doesn’t work)

Question 14

What are the different alleles of the CYP2C9 and what is their enzyme activity?

Answer 14

• 1 - wild type so has normal activity
• 2 - decreased enzyme activity
• 3 - decreased enzyme activity

Question 15

_____ are considered the junk where as ______ are transmitted into genes.

Answer 15

Introns are considered the junk (however now they are starting to believe they have more significance) where as exons are transmitted into genes.

Question 16

What is rs nomenclature?

Answer 16

Reference SNP is a naming system used in the SNP database. dbSNP is the single database for all genetic variation information.

Question 17

What is rs recommended by to be the standard nomenclature for SNPs?

Answer 17

The human Genome Variation Society

Question 18

What is an example of rs nomenclature?

Answer 18

rs4986893

Question 19

What is an example of genotype nomenclature?

Answer 19

CYP2C19 1/1 - normal
CYP2C19 1/2 - reduced enzyme activity
CYP2C19 2/3 - no enzyme activity

Question 20

What is an example of haplotype nomenclature?

Answer 20

Haplotype A

Haplotype B

Question 21

What is a set of alleles at multiple loci or areas of a gene that coexist on the same chromosome?

Answer 21

haplotype

Question 22

What are the polymorphism types?

Answer 22

Single nucleotide polymorphism (SNP)
Coding SNP
Gene deletions
Copy number variant
INDOLS

Question 23

What is an INDOL?

Answer 23

insertions or deletions of PART of a gene into another gene

Question 24

What is a SNP?

Answer 24

A single base substitution that occurs within a gene.
Several million have been identified.
SNPs may or may not alter protein synthesis or protein function.
It is the most common type of polymorphism type

Question 25

Where do coding SNP polymorphisms occur?

Answer 25

In the exon

Question 26

What are the different types of Coding SNP polymorphisms?

Answer 26

Synonymous Non-Synonymous Premature Stop Codons

Question 27

What is a synonymous SNP and name one example of it?

Answer 27

A polymorphism that does not result in a change in the amino acid sequence. Ex: ABCB1 3435 C>T still codes for Ile P-gp and it affects Efavirenz and Cyclosporine

Question 28

Does a synonymous SNP affect function of the enzyme?

Answer 28

I is not clear if there is an effect on function or expression.

Question 29

What is a non-synonymous SNP and name one example of it?

Answer 29

A polymorphism that does result in a change in the amino acid sequence. TPMT *3A

Question 30

How does the non-synonymous SNP affect the TPMT *3A

Answer 30

It changes two nucleotides and results in decreased TPMT enzyme activity. Affected drugs are azathioprine, 6-mercaptopurine. The variant is not able to metabolize and clear the medication so it causes severe bone marrow suppression. The patients dose must be reduced!

Question 31

What is the premature stop codon and what is an example?

Answer 31

Codes for TAG which results in termination of protein synthesis. CYP2C19*3 -result in no enzyme activity. Affects PPI's (Omeprazole and Lansoprazole)

Question 32

What is a gene deletion and what is an example of it?

Answer 32

It is not just a single nucleotide polymorphism but thousands of nucleotide base pairs that comprise the CYP2D6 gene are deleted. CYP2D6*5 - results in loss of function and a poor metabolizer phenotype. Affects SSRIs, tamoxifen, codeine, and Beta-blockers.

Question 33

What is a copy number variant and what is an example of it?

Answer 33

A polymorphism that results in extra copies of the CYP2D6 gene. Results in an ultra rapid metabolizer phenotype. Affects SSRIs, tamoxifen, codeine, and beta-blockers

Question 34

What does ELSI stand for?

Answer 34

Ethical, Legal, Social Issues

Question 35

What are ethical issues?

Answer 35

``` Loss of privacy Who do we test? Distributive Justice Prevention strategies (genotypic versus phenotypic prevention) Clinical Decisions ```

Question 36

What are the legal issues?

Answer 36

Legislature If testing is recommended, are clinicians liable if they do not offer test or do not order test? If adverse drug reaction occurs, who is responsible?

Question 37

What is EEOC?

Answer 37

Equal Employment Opportunity Commission

Question 38

What is GINA?

Answer 38

Genetic Information Nondiscrimination Act of 2008 protects Americans against discrimination based on genetic information when it comes to health insurance and employment.

Question 39

What are the social issues?

Answer 39

``` Health disparities Employment Insurance Societal benefits and burdens Mandatory versus voluntary screening ```

Question 40

What are the health economics and cost implications to public health of pharmacogenomics?

Answer 40

Evidence needed to support cost-effectiveness of pharmacogenetics tests. Unlikely to disrupt the current public health system because it is a gradual and incremental progression and our system has flexibility to adapt.

Question 41

We need to be concerned about ELSI issues when conducting research on the clinical utility of PG. T/F

Answer 41

True