Exam 3: Lecture 17, Clinical Applications

Question 1

Genetic models are important to….

Answer 1

ID and validate drug target
optimize leading compounds
Develop dose-response curve
Test functional consequences of genetic variations

used because experiment w/ humans cumbersome, many common genes/pathways shared between humans & animals

Question 2

Most common genetic model preclinical

Answer 2

yeast
C.elegans
Drosophila
Zebrafish
mice (most common)

Question 3

Classical Pharmacogentic approach

Answer 3

Testing DNA variations in candidate genes for association to drug response

Individual genomes correspond to such variations can be used to distinguish responders from non responders or rapid from slow metabolizers or those at risk of adverse events

Question 4

Integrative PGx approach

Answer 4

larger-scale genome-wide association approaches to elucidate the complexity of drug response

1. in vitro experiments
2. in vivo studies in preclinical models
3. in vivo human studies to ID gene associated with Therapeutic response

Use of multiple experimental approaches provides more convincing results than could a single genetic study

Question 5

PGRN

Answer 5

collaborative group of investigators with wide range of research interests, but all attempting to correlate drug response with genetic variations

conc in….

1. drug used to treat specific disorders
2. Proteins that interact with drugs

Question 6

PGRN strategies

Answer 6

Phenotype-to-genotype studies

Genotype-to-phenotype studies

Whole-genome analysis

Question 7

Phenotype-to-genotype studies

Answer 7

SNP candidate genes are associated with variations in drug response including adverse reactions.

Candidate genes are selected by constructing PK and PD pathway diagrams for the drug

Question 8

Genotype-to-phenotype studies

Answer 8

controlled clinical studies, individuals with particular genotypes are given drugs and a. drug phenotype is measured, in vivo association SNP-to-drug response

Question 9

Whole-genome analysis

Answer 9

genome-wide association studies and/or linkage analysis, IDing portions of genome that contain genetic variants associated with a specific phenotype

Question 10

levels of clinical annotation show…

Answer 10

the levels of evidence of the work that’s been done.

Level 1A = endorsed by medical society, robust data
Level 4 = least evidence

Question 11

Issues in genetics

Answer 11

Coverage and reimbursement of genetic tests

Ethical, Legal,Social

Genetic discrimination

Intellectual properties

Question 12

Genetic Info Nondiscrimination act has 2 important points…

Answer 12

Health insurance

Employment

Question 13

patients should be tested for what gene prior to starting abacavir

Answer 13

HLA-B*5701

included in black box warning

Question 14

patients positive for HLA-B*5701 should…

Answer 14

not be given abacavir