Pharmacogenomics Midterm

Question 1

What is a missense SNP?

Answer 1

amino acid substitution (either gain-of-function or loss-of-function)

Question 2

What is a nonsense SNP?

Answer 2

amino acid changes to a stop codon (loss-of-function)

Question 3

What is the Start Codon?

Answer 3

ATG

Question 4

What is the Stop Codon?

Answer 4

UAA, UAG, UGA

Question 5

What does a R2 of 1 mean for LD?

Answer 5

no recombination =complete/perfect LD

Question 6

What does a R2 of 0 mean for LD?

Answer 6

infinite recombination = no LD

Question 7

What are the substrates for Polymerase Chain Reaction(s)?

Answer 7

-DNA template
-dNTPs (dATP, dGTP, dCTP, dTTP)
-Primers: 2 short sequences specific to the region of interest
-Buffer: pH, Mg+2
-Enzyme: Taq DNA polymerase

Question 8

What are the 95% Confidence Interval values?

Answer 8

greater than 1 = significant risk effect
contains 1 = no statistical significant
less than 1 = significant protective effect

Question 9

What can DNA chips detect?

Answer 9

-detecting known SNPs or targeted SNPs
-high throughput, medium cost (low per SNP cost)

Question 10

What can Sanger Sequencing detect?

Answer 10

-can detect both known and unknown alleles
-low throughput, higher cost per base pair

Question 11

What can Next Generation Sequencing detect?

Answer 11

-whole genome/exome sequencing; detects all known or unknown alleles
-High throughput
-Higher total cost; very low cost per SNP

Question 12

What do antisense oligonucleotides (RNA interference) do?

Answer 12

reduces mRNA level so therefore less protein will be made
-useful for gain-of-function mutations
-example: Onpattro (patisiran)

Question 13

What does mRNA medicine do?

Answer 13

introduces exogeneous mRNA into the body, so cells can make proteins that are based on that mRNA that was introduced
-example: COVID-19 Vaccine

Question 14

What are Monoclonal Antibodies?

Answer 14

a type of Y-shaped protein that binds to a target protein to block the function of the target or to help recognize a specific group of cells that express the target protein
-example: PD1 and PD-L1 drugs

Question 15

What is Gene Therapy?

Answer 15

Uses a virus as a vehicle to deliver a gene
-example: adeno-associated virus Luxturna, ZOLGENSMA for SMA

Question 16

What are Stem cell (iPSCs) therapy?

Answer 16

potentially able to generate any cell type in the body to replace damaged tissue

Question 17

What are the PD-1 blockers?

Answer 17

Pembrolizumab (Keytruda); Nivolumab (Opdivo); Cemiplimab (Libtayo)

Question 18

What are the PD-L1 blockers?

Answer 18

Atezolizumab (Tecentriq); Avelumab (Bavencio); Duvalumab (Imflinzi)

Question 19

What is the difference between PD-1 and PD-L1?

Answer 19

PD-1 is found on T Cells
PD-L1 is found on cancer cells/APCs

Question 20

How does the KRAS^G12C inhibitor work?

Answer 20

AMG 510 is a small molecule that binds to KRASG12C and irreversibly inhibits it by locking it in an inactive GDP-bound state

Question 21

What are the CDK4 and CDK6 inhibitor drugs?

Answer 21

-Palbociclib, Ribociclib (Kisqali), Abemaciclib

Question 22

What are the Ribociclib + Binimetininib trials promising?

Answer 22

-promising regimen
-for melanoma patients with NRAS mutation
-0 complete response, some partial response and stable disease, a few progressive diseases