Week 6- Brittle Bones

Question 1

What cells does collagen come from?

Answer 1

Fibroblasts

Question 2

How many main types of collagen are there?

Answer 2

5

Question 3

What are the common features of collagen?

Answer 3

Triple helix
Every 3rd amino acid is glycine
Hydroxyproline and hydroxylysine presence

Question 4

What is the main feature of osteogenesis imperfects?

Answer 4

Repeated fracture of long bones as well as bone malformation

Question 5

What is the most common mutation in osteogenesis imperfects and how does this cause brittle bones?

Answer 5

Usually a mutation will replace glycine with a different amino acid that may have properties like being able to form disulfide bridges with other amino acids in other collagen chains it’s larger size causing steric hindrance etc.

This will alter the shape of the triple helix and may make it less strong etc

Question 6

Even if a patient is a heterozygote for a mutation causing osteogenesis imperfecta, why may more than ha,f their collagen be effected?

Answer 6

Collagen contains 3 chains so even if the mutation is present on only one chain, the whole molecule may be effected

Question 7

How does osteogenesis imperfecta cause weak bones?

Answer 7

Bone is formed by laying down hydroxyapatite on a ordered scaffold of collagen I. If this scaffold is disrupted, the mineralization process is also disrupted causing skeletal abnormalities

Question 8

What methods would be suitable for prenatal diagnosis of osteogenesis imperfecta? How are they carried out?

Answer 8

Genetically screening fœtal DNA obtained from chorionic villus sampling or amniocentesis.

Probes can be used that are complementary to an area where mutation is known to occur so the probes will only hybridise if the code is complimentary. Alternatively a restriction enzyme could be added if the mutation occurs at its site so only mutated DNA would be cleaved