Personalized Med and Pharmacogenomics

Question 1

What was an outcome in terms of number of human genes? How much of genome is unique between individuals?

Answer 1

20,500; .5%

Question 2

How is pharmacogenetics defined? Pharmacogenomics?

Answer 2

Relates heritable variation to inter-individual variation in drug response;
field of new drug development based on rapidly increasing knowledge of all genes in genome

Question 3

What are some stats for ADRs?

Answer 3

4th, 5th leading cause of deaths among adults;
fatal ADR freq is .3%
100,000 Americans die each year

Question 4

What happens between protein and drug that could lead to a negative result?

Answer 4

Mutation in gene that changes protein function such that binding site is compromised between drug and protein

Question 5

What can we do with drugs if patient’s genotype can be determined? How does this benefit drug companies?

Answer 5

Individualize drug therapy so each patient gets the right meds;
you avoid the high freq of ADR’s by knowing which patients you want to avoid with a specific genotype

Question 6

What is a group of genes that help with drug metabolism?

Answer 6

Cytochrome P450 proteins

Question 7

What are the four classes of function of drug metabolism?

Answer 7

1. Ultra (degrades drug so rapidly because of >2 functional alleles)
2. Extensive (normal case with 2 alleles, and drugs targeted toward this pop)
3. Intermediate (heterozygotes with one functional allele that might metabolize drug at slower rate, need lower dose)
4. Poor (very low level of enzyme activity, when conversion process could be very slow)

Question 8

What is one factor to consider in frequencies of classes of drug response?

Answer 8

Ethnic differences

Question 9

What is warfarin? What does it inhibit? What can it help treat? What are some downsides in using it?

Answer 9

Anticoagulant;
Vit K epoxide reductase;
DVT;
reacts with aspirin, ibuprofen and acetaminophen and increases risk of bleeding, eating too much VitK in foods, or too much alcohol

Question 10

What can determine patient’s response to warfarin?

Answer 10

Genetic component (some people more sensitive than others to certain dosages)

Question 11

What could the warfarin dose be dependent on?

Answer 11

Genotype of the vitamin K epoxide reductase and cytochrome P450 allele (which warfarin targets!!!)

Question 12

What is an example of personalized medicine (cancer)? What tests can be combined for this?

Answer 12

Oncology; karyotype analysis, FISH, microarray, flow cytometry, hematopathology

Question 13

What are some pros and cons of a microarray chip?

Answer 13

Cons: what genes are included, who decides, psychological burden, opt out?
Pros: early treatment to reduce intensity of disease phenotype, behavior modification (e.g. high cholesterol)

Question 14

For microarrays, what are the blank regions corresponding to? What is the technical term for this blank area? What type of test is microarray, and who does it require?

Answer 14

UPD, aka regions of homozygosity;

Genome wide scan that detects UPD and only requires study of the patient (don’t need mom and dad)

Question 15

What can a total ROH exceeding 5% of genome imply? What does having multiple large regions of homozygosity imply?

Answer 15

Identity by descent (consanguinity, incest, inbred pops, ethnic pops);
increases likelihood of expression of recessive disorder for genes within region

Question 16

What does GINA cover? What does it not?

Answer 16

Prohibits insurers from using genetic info in decisions on coverages or rates, employers can’t use genetic info for hiring, firing, promoting;
does not cover life, disability, long-term care insurance, businesses with fewer than 15 people, or health insurer from determining eligibility or premium rates based on disease presence

Question 17

What are the three screening types?

Answer 17

Prenatal screening, newborn screening, carrier screening

Question 18

What are some criteria for newborn screening?

Answer 18

Disease: clearly defined and treatable; relatively high pop incidence
Test: large scale, rapid, inexpensive; low false pos, NO FALSE NEGS; usually mandatory
Follow up: definitive diagnosis, prompt treatment, genetic counseling

Question 19

What are key factors in carrier screening?

Answer 19

Mutation must be reasonably high freq in pop; mass screening test, genetic counseling present, prenatal testing available

Question 20

What are some examples of carrier screening?

Answer 20

NP disease, Tay-Saches, Gaucher, CF, Canavan;

beta-thalassemia in Mediterranean, sickle cell in AA’s