Genomic Medicine

Question 1

Purposes of pharmacogenetics

Answer 1

• allows clinicians to base tx choices using info from genetic tests
• goal = safer, more efficient, customized drug therapies

Question 2

Describe components of drug response (3)

Answer 2

• efficacy
• adverse effects
• other side effects

Question 3

Function of P450 enzymes?

Answer 3

• responsible for a major portion of drug metabolism

Question 4

What proportion of drugs is CYP2D6 responsible for metabolizing?

Answer 4

~25%

Question 5

Best way to test for a single gene disorder w/ a known etiology?

Answer 5

PCR targeted sequencing

Question 6

Best way to test for a disorder when you’re out of ideas?

Answer 6

Whole exome (protein coding seq) or whole genome sequencing

Question 7

What type of variants are generally pathogenic?

Answer 7

• truncating variants

- eg nonsense/frameshift, canonical splice, start codon, gross deletions

Question 8

Evidence supporting neutrality (likely benign)? (4)

Answer 8

• silent variants w/o evidence of –> functional changes to protein
• pop freq too high to be consistent w/ inherited syndrome
• lack of segregation in large, known affected families
• highly variable position across spp

Question 9

Evidence of variants of uncertain significance (VUS)? (2)

Answer 9

• missense variants w/o sufficient evidence of pathogenicity or neutrality
• conflicting or insufficient functional studies

Question 10

Policy regarding Incidental Findings?

Answer 10

• should be reported

- but consent should be obtained prior to testing