Pharmacogenomics 1 Flashcards
What allele nomenclature provides information on which allele is the wild type?
A. Alpha/numeric
B. Star
C. RS
B. Star
C. RS - this is identification of the variant
SNP polymorphisms are the only type that have clinical relevance. T/F
False
What does VKORC1 code for?
It is vitamin K oxidative reductase complex 1 and it codes for the warfarin enzyme.
What do the first few letters/numbers of the allele numeric/alphabetic nomenclature identify?
The gene
What do the numbers of allele Numeric/Alphabetic Nomenclature identify?
They indicate the location of the nucleotide on the gene. ex: 1173
What does Allelle Numeric/Alphabetic Nomenclature look like?
VKORC1 1173 T
Are you able to tell which allele is the wild type or the variant on Allele Numeric/Alphabetic nomenclature?
No
What are the different ways to name a polymorphism?
Allele Numeric/Alphabetic Nomenclature SNP Nomenclature Allele Star Nomenclature Reference SNP Nomenclature (rs) Genotype Nomenclature Haplotype Nomenclature
What is an example of SNP nomenclature?
VKORC1 1173 C>T
What does the C represent in the example of VKORC1 1173 C>T?
The wildtype
What does the T represent in the example of VKORC1 1173 C>T?
The change that made the polymorphism
What is an example of Allele Star Nomenclature?
CYP2C19 *1 - wildtype
What are the different alleles of the CYP2C19 and what is their enzyme activity?
*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)
What are the different alleles of the CYP2C9 and what is their enzyme activity?
- 1 - wild type so has normal activity
- 2 - decreased enzyme activity
- 3 - decreased enzyme activity
_____ are considered the junk where as ______ are transmitted into genes.
Introns are considered the junk (however now they are starting to believe they have more significance) where as exons are transmitted into genes.
What is rs nomenclature?
Reference SNP is a naming system used in the SNP database. dbSNP is the single database for all genetic variation information.
What is rs recommended by to be the standard nomenclature for SNPs?
The human Genome Variation Society
What is an example of rs nomenclature?
rs4986893
What is an example of genotype nomenclature?
CYP2C19 1/1 - normal
CYP2C19 1/2 - reduced enzyme activity
CYP2C19 2/3 - no enzyme activity
What is an example of haplotype nomenclature?
Haplotype A
Haplotype B
What is a set of alleles at multiple loci or areas of a gene that coexist on the same chromosome?
haplotype
What are the polymorphism types?
Single nucleotide polymorphism (SNP) Coding SNP Gene deletions Copy number variant INDOLS
What is an INDOL?
insertions or deletions of PART of a gene into another gene
What is a SNP?
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
Where do coding SNP polymorphisms occur?
In the exon
What are the different types of Coding SNP polymorphisms?
Synonymous
Non-Synonymous
Premature Stop Codons
What is a synonymous SNP and name one example of it?
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
Does a synonymous SNP affect function of the enzyme?
I is not clear if there is an effect on function or expression.
What is a non-synonymous SNP and name one example of it?
A polymorphism that does result in a change in the amino acid sequence.
TPMT *3A
How does the non-synonymous SNP affect the TPMT *3A
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!
What is the premature stop codon and what is an example?
Codes for TAG which results in termination of protein synthesis.
CYP2C19*3 -result in no enzyme activity.
Affects PPI’s (Omeprazole and Lansoprazole)
What is a gene deletion and what is an example of it?
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.
What is a copy number variant and what is an example of it?
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
What does ELSI stand for?
Ethical, Legal, Social Issues
What are ethical issues?
Loss of privacy Who do we test? Distributive Justice Prevention strategies (genotypic versus phenotypic prevention) Clinical Decisions
What are the legal issues?
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?
What is EEOC?
Equal Employment Opportunity Commission
What is GINA?
Genetic Information Nondiscrimination Act of 2008 protects Americans against discrimination based on genetic information when it comes to health insurance and employment.
What are the social issues?
Health disparities Employment Insurance Societal benefits and burdens Mandatory versus voluntary screening
What are the health economics and cost implications to public health of pharmacogenomics?
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.
We need to be concerned about ELSI issues when conducting research on the clinical utility of PG. T/F
True
