Genomes and Medicine

Question 1

What are the properties of common risk alleles?

Answer 1

• Explain far less than half of genetic basis for common disorders
• Small effect sizes and disease OR
• Few ppl have numerous common risk alleles for given disorder
• Often found in noncoding regions of genome

Question 2

Discuss the limitations of Direct to Consumer Genetic testing for common disorders.

Answer 2

• Even with same genetic data, there can be different models to produce different risk scores. Different interpretations.
• No scientific evidence that genetic testing will improve health

Question 3

Discuss the legislation related to genetic testing in the US

Answer 3

• 2008 GINA - Genetic Information nondiscrimination act: prohibits discrimination in health coverage and employment based on genetic information
• prohibits firing and not hiring, workplace discrimination, based on genetic info

Question 4

Describe mutation specific therapies for cystic fibrosis.

Answer 4

• Mutation G551D is defective for Cl- transport.

- Ivacaftor-potentiator drug to improve mutant and wild CFTR activity for p.G551D mutation

Question 5

Describe Nonsense suppressor therapies

Answer 5

• drugs that promote read through of premature stop codons
• Ongoing clinical trials with second gen therapies for DMD and CF
• Drawback: to go through normal stop codons resulting in longer than usual protein

Question 6

Discuss the pharmacokinetics of irinotecan. How do genetics affect it’s rate of metabolism?

Answer 6

• UGT1A1 encodes an enzyme that makes the active form of irinotecan easier to eliminate
• Common genetic variants influence the activity of UGT1A1 in the population
• People can be fast or slow metabolizers of the active form of irinotecan
• Slow metabolizers have a higher rate of adverse effect when treated with irinotecan (diarrhea and myelosuppresion)

Question 7

Discuss the pharmodynamics of tamoxifen.how does genetics influence its effectiveness?

Answer 7

No effect in estrogen receptor negative breast cancer. Not inhibited by tamoxifen.

Question 8

Describe national initiative to research therapies for rare diseases. What is drug repurposing and drug rescue?

Answer 8

• National Center for Advancing Translational Research (NCATS)-research for rare diseases
• Drug repurposing: small molecules and biologics approved to treat a disease or condition to see if they are safe and effective for treating other diseases.
• Drug rescue: small molecules and biologics whose development was abandoned before they could be approved by theU.S. Food and Drug Administration