sdl6

SDL 6 - Epigenetics

i just include sme imprtnt points.. still need more time for study.. hope tis helps.. :)

X-inactivation is the silencing of one X-chromosome in the somatic cells of normal females (not males), so that only one is active. This is needed for dosage compensation (balance) as male somatic cells only have one X-chromosome.

Mechanisms of imprinting around IGF2/H19 axis of 11p15.5
IGF2 and H19 are co-regulated by each other via the enhancer competition model which keeps only one active and the other not, on a given allele (reciprocal imprinting)

H19 which is maternally expressed is activated by a downstream enhancer & keeps igf2 inactivated. In paternal allele, imprinting results by methylation of H19 blocking its activation and allowing the enhancer to bind to the adjacent igf2 gene activating it.

A small subgroup of sporadic BWS cases shows biallelic expression of IGF2 and silencing of H19, accompanied by a paternal methylation pattern on both chromosomes, suggesting that an imprinting control region (BWSIC1) is inactive in such individuals

Methylation can be ass. with gene silencing and activation
e.g. methylation of anti-sense strand leads to activation of gene, methylation of sense inactivates it

Characteristics in a system needed for maintenance of imprints
Imprint needs to be stable such that it is maintained during cell division of all somatic cells. Imprint must be erased in the germ cells, hence it must be a reversible imprint. Requires erasure and re-establishment (see notes)

inactivation center e.g. X-inactivation center which involves in silencing
diseases of imprinting and imprinting in cancer all in notes..

add. alzheimer's pbl.. :)

Familial early-onset of AD:
APP(21), presenilin 1(14) and 2(1) mutations

APP (21q)
BA4 amyloid deposits encoded by APP
>6 mutations found
B-secretase cuts 671/2
A-secretase cuts 687/8
G-secretase cuts 712

Amyloid B is formed by cutting of 671/2 by B-secr then cut by G-secr

if g-secr cuts and 712/3th a.a. residue, short AB(1-40) but if at 714th, long AB(1-42/3) *long AB leads to AD

APP mutations
mutations potentiate B, inhibit A and alter position of cut by G in
Swe, Fle, Ldn/Fld resp. Presenilin mutations lead to altered processing (more AB(1-42/43) formed)

amyloid cascade hypothesis
(diagram frm journal by Hardy)

Tau hypothesis and late-onset sporadic AD all in notes~

I think that’s all I can foster.. all the best and good luck.. >.<