Tutorial 4 - Osteogenesis Imperfecta

Question 1

Which is bigger, cysteine or glycine?

Answer 1

Cysteine, bigger R group

Question 2

What causes osteogenesis imperfect?

Answer 2

Point mutations in the gene for Type 1 collagen.

G replaced by T.

Question 3

What does the point mutation in osteogenesis imperfecta cause?

Answer 3

Glycine is substituted with cysteine.

Larger AA formed which causes kink in normally straight triple helix. This consequently affects the assembly of collagen fibres.

Question 4

What does the sulphydryl group mean?

Answer 4

Cysteine has a reactive sulphydryl group in its side chain.

Means that inappropriate disulphide bonds form between the 2 a-1 chains in the helix.

Question 5

What is noticed when examining the cross linked polypeptides of the mutated collagen?

Answer 5

They move much more slowly than the individual chains (normal) in the presence of SDS (detergent).

Speed of migration of proteins on electrophoresis depends on size and not charge)

Question 6

What are the consequences of deformed collagen?

Answer 6

1. Weak, brittle bones, prone to fracture.

2. Bone formation through hydroxyapatite on an ordered collagen-1 scaffold is defected.

Question 7

What are the 2 ways to prenatally diagnose Osteogenesis Imperfecta?

Answer 7

CVS

Amnioscentesis, amplified by PCR.