Mutational Mechanisms and Disease

Question 1

Loss of Function Mutation:

• Def?
• Ex? (5)

Gain of Function:
Ex: (2)

Answer 1

• Majority of mutations affects function of protein; single gene disorders almost always = altered function
• Duschenne, a-thalassemia, Turner, HNPP, Osteogenesis Imperfecta Type 1
• Hb Kempsey; Charcot-Marie Tooth; PMP gene duplication = increased function

Question 2

Novel property mutation:
- Ex? (2)

Altered Expression:
- Ex? (1)

Trinucleotide Repeats Locations? (5)

Answer 2

• Sickle Cell; osteogenesis imperfecta 2,3,4
• Hereditary Persistance of Fetal Hb
• 5’ UTR = Fragile X
• Intron = Frederick Ataxia; Myotonic Dys 2
• Exon = Huntingtons
• 3’ UTR = Myotonic Dys 1

Question 3

• Mutations that Interrupt Protein Production examples:
  1. ) Transcription?
  2. ) Translation?
  3. ) Folding?
  4. ) Post Mod?
  5. ) Monomer Assembly?
  6. ) Subcellular Localization?
  7. ) Cofactor Problem?
  8. ) Functional Issues?

Answer 3

1. ) Thallessemia / Hered. Fetal Hb
2. ) Thallesemia via frameshift
3. ) Hemoglobinopathy
4. ) I Cell Disease
5. ) Osteogenesis Imperfecta
6. ) Familial hypercholestemia
7. ) Homocystindrea
8. ) Hb Kempsey