Tutorials 4-5 Flashcards
What can neutralise proteins that are separated due to size in electrophoresis?
SDS - sodium dodecyl sulphate
What mutation causes OI and on what gene?
Single base substitution from GGC to TGC on COL1A1 gene.
What does the OI mutation result in?
Cysteine is formed instead of glycine.
What are the implications of having cysteine present instead of glycine?
Larger amino acid so caused steric hindrance as only amino acid that can fit inside the triple helix is glycine (only hydrogens can fit in the middle). Also causes inappropriate formation of disulphide bridges between the two alpha chains.
What do mutations to proline cause?
Structural problems - collagen may not pack together properly.
Alongside glycine, what amino acids are normally found in collagen?
Modified amino acids - hydroxyproline and hydroxlysine
How many types of collagen are there?
5
Which collagen type is OI linked with?
Collagen I
Why is collagen important?
Important in mechanical and tensile strength of muscle tissue and bones.
How is collagen formed?
- First synthesised on free ribosomes then translocated to the rER
- Recognised as a secretory protein
- Pre-pro collagen is cleaved off to form pro-collagen
- Pro-peptides on ends of each chain are lost after collagen formation
What are the functions of pro-peptides? (2)
Direct collagen formation and prevent formation of fibrils (insoluble proteins) in cells - a build up of fibrils can lead to cell death.
What pattern of inheritance does OI follow?
Autosomal dominant.
Is “dominant negative” so even if heterozygous for mutant gene, patient will still be affected.
What is bone normally consisted of?
Hydroxyapatite (form of calcium phosphate) and collagen. It is then mineralised.
How does OI affects bone structure?
Abnormal collagen causes abnormal mineralisation, leading to skeletal abnormalities and bone weakness.
Symptoms of OI? (6)
- Weakened bones
- Shortened height
- Blue sclera (white of the eye)
- Loss of hearing
- Hyper-mobility
- Poor teeth development
