Exam 3: Lecture 15/16, Exploring Pharmacogenetics and Pharmacogenomics

Question 1

International HapMap

Answer 1

Goal: develop haplotype map of human genome that describes patterns of human DNA sequence

Aim: Guiding the design and analysis of medical genetic studies of clinical phenotypes

Question 2

Potential of Genome?

Answer 2

Prognostic = prediction tool
Diagnostic = ID tool
Therapeutics = manipulation tools

Question 3

Pharmacogenomics =

Answer 3

therapeutics called personalized medicine

Question 4

Genotype

Answer 4

Genetically determined

heritable genetic ID, particular gene or set of genes carried by individual

Question 5

Phenotype

Answer 5

physically observable

constellation of observable traits

Question 6

Pharmacogene?

Answer 6

gene involved in response to a drug

Question 7

Pharmacogenetics target/potential

Answer 7

individuals

predict drug response/match drugs and asses disease risk

study of inherited differences in drug metabolism and response

Question 8

pharmacogenomics target/potential

Answer 8

population

reduce drug diagnosis and development time

general study of all of the many different genes that determine drug behavior

Question 9

genetic biomarkers

Answer 9

measurable DNA and/or RNA characteristic that are indicators of normal/pathogenic processes and/or response to therapeutics

Question 10

Biomarkers used for….

Answer 10

indication
safety
dosing
info

Question 11

Patient selection: responder =

Answer 11

should be admin

Question 12

Patient selection: non responder =

Answer 12

should not be admin

Question 13

Manhattan plot

Answer 13

X-Axis = gene
Y-axis = p value

Question 14

Allele nomenclature

Answer 14

1st letter/number ID the gene

number gives location of nucleotide of gene

last letter represent nucleotide, second letter represents nucleotides that has changed to result in SNP

Question 15

Which genotypes might be useful in determining optimal initial dose of warfarin?

Answer 15

VKORC1 and CYP2C9

Question 16

CYP2C9 *1

Answer 16

*1 allele, wild type enzyme activity

Question 17

CYP2C9 *2

Answer 17

*2 allele, decreased enzyme activity

C > T

Question 18

CYP2C9 *3

Answer 18

*3 allele, decreased enzyme activity

A > C

Question 19

Which variants are poor metabolizers for warfarin?

Answer 19

*2 and *3 variants

so require lower dose

Question 20

carriers of what genetic variant require lower dose warfarin due to higher sensitivity?

Answer 20

1639 G > A in VKORC1

Question 21

SNP Selection: Things to consider

Answer 21

Validation
Informative
Potential functional
Previously associated

Question 22

If alleles present in >1% of heterozygous individual in a population, the variation is called….

Answer 22

polymorphism

Question 23

If alleles are present in <1% of heterozygous individuals in a population, variation is called….

Answer 23

mutation

Question 24

Most common type of genetic variation among people?

Answer 24

SNP = single nucleotide polymorphism

Question 25

Synonymous SNP

Answer 25

SNPs in protein-coding axons that do not change the amino acid due to redundancy of genetic code

no consensus of effect on enzyme activity

Question 26

Non-synonymous SNP

Answer 26

SNPs in protein-coding axons that change the amino acid

decrease enzyme activity

Question 27

Patients with TPMT SNP mutation taking Azathioprine should take a dose that is….

Answer 27

1/10th to 1/15 of standard dose to avoid toxicity due to low TPMT activity

Question 28

Premature stop codon SNP

Answer 28

SNPs in protein-coding axons that no longer code and result in termination of protein synthesis

no enzymatic activity