Brittle Bones Flashcards
Why are some people with brittle bone disease suspected of being an abuse victims
Main feature of disease is repeated fracture of long bones and also malformed bones
Structure of collagen
Type 1 collagen consists of 3 alpha chains (2 alpha1 and one alpha2).
What happens to collagen structure in brittle bone disease
Glycine is substituted by cysteine. Every 3 codons is glycine which normally allows for tight packing. Cysteine is larger and this causes a kink in a normally straight triple helix. Cysteine also contains reactive sulphhydroxyl group which allows inappropriate disulphide bridges to form
What does 2-mercaptoethanol do
sulphydryl reagent which reduces the disulphide bonds between cysteine residues in proteins, i.e. -S-S- becomes 2 -S-H in the presence of the reagent. .
How does SDS PAGE gel electrophoresis work
SDS is used to denature protein and this coats protein with negative charge along its length and denatures it and neutralises charge on protein which causes it to separate due to size
Why is a bulge formed/ the assembly of type 1 collagen changed?
Glyx-X-Y and glycine in centre of triple helix and glycine has H as side chain and no other amino acids will fit. Will cause a triple helix with a bulge and so collagen cannot be packaged together properly.
why is this a dominant pattern of mutation?
only half of coA1 proteins are mutated but all fibrils will be affected due to packing . Kink in any chain will affect the structure of collagen packaging
why might the predicted change cause skeletal abnormalities and brittle bones?
Initially skeleton is laid down as collagen and later minelerised. If collagen structure is defective the bone structure will be defective. As you built up collagen structure if it is not built up correctly, the bone will not be built up correctly.
how is the formation of the bone formed?
Bone is formed by laying down hydroxyapatite ( a form of calcium phosphate) on an ordered scaffold of collagen-I. The abnormal collagen structure leads to defects in this mineralisation process so that th patient ends up with skeletal abnormalities and especially with the eyes, teeth, skin and ears.
Suggest a suitable prenatal diagnostic test which could be used to determine whether a foetus will inherit Osetegenesis Imperfecta from an affected parent.
Genetic screening of foetal DNA obtained by chronic villus sampling or amniocentesis and amplified by PCR. Specific probes could be used which were complementary to part of the DNA sequence where a mutation was known to occur: probe will only hybridise to the exact complementary sequence, enabling normal and mutant genes to be distinguished. Use PCR. If mutation is already present in family, then use that as DNA probe.
