Mutational Mechanisms & Disease

Question 1

Duchenne Muscular Dystrophy

Answer 1

LOF
• Large deletions (multiple exons) 
• Nonsense (stop) mutations / frameshift mutations
premature termination
• (in-frame deletions = milder Becker muscular dystrophy)
• X-linked inheritance
Pseudohypertrophy of the calves
Gowers maneuver

Question 2

Cancer (in general)

Answer 2

Heterochronic (oncogene that should be turned off is switched on)

Question 3

Huntingtons disease

Answer 3

Novel function

More CAG repeats = more glutamine residues on protein = toxic function

Question 4

Achondroplasia

Answer 4

GOF

FGFR3 is constitutively active –> shortened bones

Question 5

alpha-thalassemia

Answer 5

LOF

deletion of gene coding for alpha globin

Question 6

Fetal Hemoglobin persistance

Answer 6

Heterochronic

The switch from gamma to beta doesn’t occur

Question 7

Sickle Cell

Answer 7

Novel function

hemoglobin gains new function of polymerizing when unbound to O2

Question 8

Charcot-Marie-Tooth

Answer 8

GOF
duplication for PMP22 (gene for peripheral myelin)
weakness & neuropathy in the extremities

Question 9

Alzheimer’s

Answer 9

GOF

In individuals with DS (+21) they have an additional copy of APP

Question 10

Hereditary Rb

Answer 10

LOF

Deleted / impaired Rb gene (tumor suppressor)

Question 11

HNPP

Answer 11

LOF

deletion of PMP22 gene (opposite of CMT)

Question 12

Osteogenesis Imperfecta

Answer 12

LOF