Lecture 6 Precision Medicine - Beck

Question 1

*Define GWAS, list strengths and weaknesses

Answer 1

GWAS: genome-wide association studies: is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.

• links COMMON GENETIC VARIANTS with COMPLEX TRAITS, ID genes associated with disease.
• pros: Clinical translation of findings via clinical advances (biomarkers, therapy) and personalized medicine
• cons: difficult to link genotype to phenotype, how to move from stastistical significance to causative.

Question 2

*What is a Manhattan Plot?

Answer 2

• readout from GWAS showing SNP data arranged by XRs, correlated to disease phenotype.
• SNP freqs.

Question 3

*Define SNP

Answer 3

Single Nucleotide Polymorphism: marker of genetic inheritance.

• different variants within the same gene among individuals
• can be synonymous or nonsynonymous
• measured by DNA sequencing

Question 4

Example of a GWAS

Answer 4

• patients with schizophrenia vs controls = IDed complement component 4, which plays a role in synapse pruning in the brain. This process is impaired in schiz
• KO C4 gene in mice to determine biological role
• example of successful GWAS

Question 5

Define phenotype/genotype.

How are they distinguish? How is PCx used in the clinic today?

Answer 5

• genotype: the genetic makeup of an individual
  phenotype: the physical manifestation of genetic information.
• used to access toxicity vs benefit

Question 6

Pharmacogenomics

Answer 6

A specialized use of SNP analyses focused on genes involved in drug action and toxicity
- The study of how one’s genetic makeup influences responses to drug treatment (both drug action and drug toxicity) = getting right drug to the right person
- ID benefit vs toxicity
Pros: improve therapies, lower pharmacy cost
Cons: complex and doesnt explain all variability

Question 7

*Provide 3 examples of notable pharmacogenomics and sequencing tests
in clinical use that were discussed in the lecture.

Answer 7

Used for DOSE ADJUSTMENT IN CLINIC

1. TPMT Assays: Screens for deficiency in TPMT, which has a toxic effect if given the drug 6-MP in acute lymphoblastic leukemia
2. Mutations in EGFR respond better to gefitinib in lung cancer
3. cyp2d6 mutation may cause pts to metabolize certain drugs at different rates than normal (ex tricyclic antidepressants)

Question 8

*As discussed in class, define precision medicine and list 3 of the 8 components needed to bring precision medicine to the clinic.

Answer 8

Precision medicine: Medical care designed to
optimize efficiency or therapeutic benefit for particular groups of patients, especially by using genetic or molecular profiling
Components: willing patients
bioinformatics analysis
patient samples
drug testing
patient monitoring