Pharmacogenomics 1 Flashcards

1
Q

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

A

B. Star

C. RS - this is identification of the variant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

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

A

False

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does VKORC1 code for?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

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

A

The gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does Allelle Numeric/Alphabetic Nomenclature look like?

A

VKORC1 1173 T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

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

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the different ways to name a polymorphism?

A
Allele Numeric/Alphabetic Nomenclature
SNP Nomenclature
Allele Star Nomenclature
Reference SNP Nomenclature (rs)
Genotype Nomenclature
Haplotype Nomenclature
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is an example of SNP nomenclature?

A

VKORC1 1173 C>T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A

The wildtype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

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

A

The change that made the polymorphism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is an example of Allele Star Nomenclature?

A

CYP2C19 *1 - wildtype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

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

A

*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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

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

A
  • 1 - wild type so has normal activity
  • 2 - decreased enzyme activity
  • 3 - decreased enzyme activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is rs nomenclature?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

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

A

The human Genome Variation Society

18
Q

What is an example of rs nomenclature?

A

rs4986893

19
Q

What is an example of genotype nomenclature?

A

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

20
Q

What is an example of haplotype nomenclature?

A

Haplotype A

Haplotype B

21
Q

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

A

haplotype

22
Q

What are the polymorphism types?

A
Single nucleotide polymorphism (SNP)
Coding SNP
Gene deletions
Copy number variant
INDOLS
23
Q

What is an INDOL?

A

insertions or deletions of PART of a gene into another gene

24
Q

What is a SNP?

A

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

25
Q

Where do coding SNP polymorphisms occur?

A

In the exon

26
Q

What are the different types of Coding SNP polymorphisms?

A

Synonymous
Non-Synonymous
Premature Stop Codons

27
Q

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

A

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

28
Q

Does a synonymous SNP affect function of the enzyme?

A

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

29
Q

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

A

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

30
Q

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

A

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!

31
Q

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

A

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

32
Q

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

A

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.

33
Q

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

A

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

34
Q

What does ELSI stand for?

A

Ethical, Legal, Social Issues

35
Q

What are ethical issues?

A
Loss of privacy
Who do we test?
Distributive Justice
Prevention strategies (genotypic versus phenotypic prevention)
Clinical Decisions
36
Q

What are the legal issues?

A

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?

37
Q

What is EEOC?

A

Equal Employment Opportunity Commission

38
Q

What is GINA?

A

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

39
Q

What are the social issues?

A
Health disparities
Employment
Insurance
Societal benefits and burdens
Mandatory versus voluntary screening
40
Q

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

A

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.

41
Q

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

A

True