osteogenisis imperfecta

what is a dominant negitive mutation

a mutation where the gene product no only looses its own function but prevent ther genes from functioning correctly

what type of mutation is ostrogenisis imperfects

a dominant negitive mutation of collogen

decsribe the structure of collogen

3 alpha chains

wat do all the alpha chains of collogen contain

triple helix glycogen and then 2 other amino acids

how many types of posteogenisis imperfecta are there

4

in what location do the mutations for osteogenisis imperfecta occour

COL1A1 and COL1A2 genes

what do the COL1A1 and COL1A2 genes encode

type 1 collogen

the 4 types can be catogrised into 2 groups what are they

the included type

what is the included type

when the abnormal gene prduct is included into the matrix

what is the exluded type

whe the abnormal gene prduct isnt included in the matrix

describe type I

the mild type

where does the mutation ccour in type I

in the COL1A1 gene

what is the phenotype of type I

hearing loss, normal stature, little bone deformity

describe the effect of the mutation in type I

the allele is exluded so the atrix contains only 50% of the nomall amount of collogen

describe type II

the leathal form

what is the phenotype for type II

the ribs are too weak to support breathing therfore death

descrie type III

the servear form

what mutation occours in type III

point mutation in COL1A2 and COL1A1 gene

describe the phenotype for type III

marked bone deformity, short stature, beaded ribs

describe the effect of the mutation in type III

the abnoral type 1 colloen is included resulting in a defective matrix

descriebe type IV

mild to moderate

what mutation ocours in type IV

point utations in COL1A2 gene

whats the pheotype of type IV

small amounts f bne deformity, variabl sort stature, some hearing loss

is type IV an included or excluded type

included

what is the effect of a point mutation in the glycime of collogen

slower rate of triple helix formation, lower triple helix thermal stablitiy

what are the factors that effect the severtiy of osteogenisis imperfecta

which gene is mutated, the nature of the mutation

which gene causes the worst phenotype

COL1A1 > COL1A2

how does the nature of the mutation effect the severity

which amino acid replaces the glycine

what diffrent effect may occour on the mutation of the glycine

diffrent size mutations, the position of the mutatin

how does the location of the mutation on the triple helix effect the severity

the triple helix is assempbled from the end if the mutation is at th begining it will have mor of an impact

decribe biophosphates as a treatment for ostiogenisis imperfecta

reduces osteoclast activity but efeicnty is only moderate in children and not yet proven in adults

describe anabolic therapy as a treatent for osteogenisis imperfecta

relevent humn growth hormone to aleviate short stature however theres risks assosiated with long term use and withdrawls