Pharmacogenetics and Multifactorial inheritance

Question 1

Phenocopy

Answer 1

environmentally caused phenotype that mimics genetic version of the trait

-ie: thalidomide - induced limb malformation vs genetically induced

Question 2

locus heterogeneity

Answer 2

same/similar disease caused by mut in alleles at diff locations in 1 gene or many genes

Question 3

higher concordance rates indicates what?

Answer 3

genetic variation contributes to variation in risk more than variation in non genetic factors

Question 4

higher coorelation among MZ and DZ twins for a quantitative trait suggests what?

Answer 4

genetic variation is relatively more important than variation in non genetic factors
(these sib more likely to both get disease)

Question 5

Heritability estimates describe what?

Answer 5

Both genetic and non genetic factors adding variance in a trait.

Question 6

high heritability indicates what?

Answer 6

diff among indiv with trait largely attributed to diff in genetic makeup.

Question 7

CYP3A
substrates?
inhibitor?
inducers?

Answer 7

substrates:
cyclosporin (immunosuppresant agent)

Inhibitor:
Ketoconazole (antifungal agent)
grapefruit juice

Inducers:
rifampin

Question 8

CYP2D6
substrates?
Inhibitors?

Answer 8

substrates:
tricyclic antidipressants
codein (activator)

Inhibitor:
quinidine
fluoxethine
paroxetine

Question 9

CYP2C9

Substrate?

Answer 9

Warfarin

Question 10

NAT

Substrate?

Answer 10

Isoniazid (for TB treatment)

Question 11

VKORC1

Inhibitor?

Answer 11

Warfarin

Question 12

TPMT

Answer 12

6-mercaptopurine

6-thioguanine

Question 13

G6PD

Answer 13

Sulfonamide
Dapsone

(indiv who are G6PD deficient are susceptible to hemolytic anemia)

Question 14

Pharmacokinetics

Answer 14

(removal/movement of drugs)

-rate at qhich body absorbs, distributes, metabolize, or excretes drugs (ADME)

Question 15

Pharmacodynamics

Answer 15

(effect)

observed biological effect of drug

Question 16

phase I

Answer 16

pharmacokinetic

• attach polar group to compound to make it more soluble (usually hydroxylation) -> elimination

Question 17

phase II

Answer 17

pharmacokinetic

-attach a sugar acetyl group to detoxify drug -> eliminate

Question 18

cytochrome P450 (CYP450)

• (very)general function
• how many families?

Answer 18

• good detoxifying enzymes - inactivate drugs

- 3 main families: CYP1, CYP2, CYP3

Question 19

What would result if there was a ____ mutation on the CYP2D6 gene?

1. Frameshift
2. SPlicing defect
3. Missense
4. Copy number allele

Answer 19

1. Frameshift: alter reading frame - NO ACTIVITY
2. SPlicing defect: skip exons/alter reading frame - NO ACTIVITY
3. Missense: alter protein function - REDUCED ACTIVITY
4. Copy number allele: increase gene copy alleles - INCREASED

Question 20

Incomplete penetrance

Answer 20

not everyone with predisposing gene variant develops disease

-ie type I diabetes

Question 21

Variable expressivity

Answer 21

no people with same genetic variant have exact same disease characteristics

Question 22

2 types of heterogeneity

Answer 22

same similar diseases can be caused by:

1. allelic: diff mutation at same allele
2. locus: mutation of alleles at diff locations