Exam 1 Review Flashcards
How many codons are there in the genetic coding system?
64 codons
What are the 3 stop codons in the genetic coding system?
- UAA
- UAG
- UGA
What is the start codon in the genetic coding system?
ATG
How many amino acids are there?
20 amino acids
What is a non-synonymous SNP?
changes amino acid in the protein
What is a missense SNP?
non-synonymous
- Missense is an amino acid substitution
- It could lead to either a gain of function or loss of function for the protein depending on what amino acid it changes to
What is a nonsense SNP?
non-synonymous SNP
- Nonsense SNP changes an amino acid to a stop codon
- This normally leads to a loss of function
What is a synonymous SNPP?
- Does not change amino acids
- Usually does not change the gene/protein function
What is a silent SNP?
synonymous SNP
non-amino acid change
Where must an SNP occur for the change in function to have a clinical effect?
SNP must be in an EXON because the exons are what are expressed.
What does the c in c.1297G>A indicate?
The change is in the coding DNA sequence
count from the first nucleotide of coding DNA sequence (ATG)
What does the p in p.Val433Met indicate?
The change is in protein position
Can a rare allele in one population be a common allele in another population?
Yes
What is linkage disequilibrium?
non-random association of alleles at different loci on the same chromosome
How does infinite recombination impact LD?
There is no LD
How does no recombination impact LD?
There is complete/perfect LD
How does recombination occurring in a portion of chromosomes impact LD?
There is incomplete LD
What does complete linkage mean?
- Means that LD = 1
- the DNA is inherited by segments (aka the alleles are ALWAY inherited together)
- each segment is called a haplotype block
What does no linkage indicate?
- LD = 0
- The alleles are never inherited together
The distance between the two loci is large
What does R^2 indicate?
How strong the correlation between two variables is
Measures the strength of LD
List what each R^2 value indicates about LD:
- R^2 = 0 –> no LD
- R^2 = 1 –? complete/perfect LD
- R^2 > 0.8 –> strong LD
Does p value measure strength of an association?
- No
- It can be affected by sample size. (Larger sample size, lower p )
- It can be affected by allele frequency
List what each p value indicates:
- P > 0.1 no significant association
- 0.05 < P < 0.1 marginal association
- P < 0.05 significant association
- P < 0.01 very significant association
What is the P value used for whole genome sequencing data?
5x10^-8
- Corrected significant GWAS P value
Describe what the various 95% CI values indicate:
- 95% CI greater than1 –> significant risk effect
- 95% CI contains 1 –> no statistical significance
- 95% CI less than 1 –> significant protective effect
What is polymerase chain reaction (PCR) used for?
DNA amplification
What substrates are required for PCR?
- DNA template
- dNTPs (dATP, dGTP, dCTP, dTTP)
- Primers: 2 short sequences specific to the region of interest
- Buffer: pH, Mg2+
- enzyme: Taq DNA polymerase
What can DNA Chip sequencing detect?
- KNOWN SNPs or targeted SNPs
High-throughput, but cheap
What can Sanger Sequencing detect?
- Can detect BOTH KNOWN AND UNKNOWN alleles
- SNPs, indel, small CNV
low throughput, but more expensive per base pair
What can next generation sequencing detect?
- all known or unknown alleles
- whole genome/whole exome
- detects all kinds of polymorphisms
high-throughput, higher total cost
Describe the functions of PCSK9:
- PCSK9 decreases LDL receptor proteins via lysosomal degradation. LDL-R recycling is also blocked
- Decreased LDLR leads to increased LDL-C concentrations (because they can’t bind to LDL-R)
What is ICER?
incremental cost-effectiveness ration
What is QALY?
quality-adjusted life-year
Explain RNA interference (antisense oligonucleotides (ASO)) drugs:
- blocking the mRNA directly to reduce the protein being made from that particular mRNA
- halts the process of creating a disease-causing protein
- Onpattro (patisiran) - an RNAi drug for people with hereditary transthyretin-mediated amyloidosis (rare and deadly)
Explain mRNA medicine:
- introduce exogenous mRNA into the body so cells can make proteins based on the introduced mRNA
- COVID-19 vaccine
Explain monoclonal antibodies and antibody-drug conjugates (ADCs):
- A type of Y shape protein that specifically binds to its target (target protein) to block the function of that target protein OR help to recognize a specific group of cells (cancer cells) that express the target protein
- PD1 and PD-L1 drugs are common mabs
Explain gene therapy drugs:
- virus as a vehicle to deliver gene
- FDA-approved adeno-associated virus (AAV) drug Luxturna to treat a rare form of inherited vision loss
Explain CRISPR-mediated gene-editing and mutation-repair:
just give an example
- a trial of an experimental CRISPR-Cas9 therapy for the blood disorder B-thalassemia has been launched
Explain stem cell (iPSCs) therapy:
- most are still being developed
- has the potential to generate many cell types in the body to replaced damaged tissue
What are the 4 steps in mRNA medicine?
- scientists generated an mRNA sequence that codes for the virus spike protein
- the RNA sequence, a blueprint for making the spike, is swathed in a lipid coating for delivery
- Once it arrives, cells read the information in the mRNA sequence to produce millions of copies of the spike protein
- the protein fragments spur the immune system to produce antibodies that can protect when a real virus enters the body
- making the exogenous mRNA stable is key
- finding the right coating to deliver them into the cell is critical
Explain the process of gene therapy with adeno-associated virus (AAV):
- Transgene is packaged into AAV vectors
- Through a one-time IV infusion, AAVs carrying the transgene target the liver
- In the liver, AAV vectors deliver transgene to the nucleus of liver cells to enable production of therapeutic protein
What kind of drug is zolgensma?
- Gene therapy with AAV
- biologic drug consisting of AAV9 capsids that contain a SMN1 transgene along with synthetic promoters
this drug increases SMN1 to increase survival of motor neurons
How does the CRISPR/Cas9 DNA editing technique work?
- A cell is transfected with an enzyme complex containing: guide molecule, healthy DNA copy, and DNA-cutting enzyme
- A specially designed synthetic guide molecule finds the target DNA strand
- An enzyme cuts off the target DNA strand
- the defective DNA strand is replaced with healthy copy
List the PD-L blockers:
- pembrolizumab (Keytruda)
- nivolumab (Opdivo)
- cemiplimab (Libtayo)
List the PD-L1 blockers:
- atezolizumab (Tecentriq)
- avelumab (Bavencio)
- durvalumab (Imfinzi)
What is synthetic lethality and why do we induce it?
- The combination of two separate mutations (BRAC and PARP) lead to cell death while either mutation alone is not lethal.
- We can exploit this to selectively kill cancer cells while sparing normal cells.
List the BRAC1 inhibitors:
- niraparib
- olaparib
- rucaparib
- talazoparib
List the drugs that target the KRAS mutation:
- binimetinib
- trametinib
- cobimetinib
What is MRTX849/AMG-510 and what does it do?
- Lumakras/sotorasib
- Blocks KRAS signaling and promotes apoptosis in KRAS G12C
ONLY FOR G12C
List the CDK4 and CDK6 inhibitors:
- palbociclib
- ribociclib
- abenaciclib
