Trigger 10: Prader-Willi syndrome Flashcards
phenotypes associated with Prader-Willi syndrome
- short stature - hypotonia (poor muscle tone) - small hands and feet - obesity - mild- moderate learning difficulties
how common is Prader-Willi
1/15,000
Prader-Willi is caused by a defect in an
imprinted gene
imprinting
You usually get one copy of genes from your mother and one from your father, in imprinting, one of the genes are silenced. - genes are expressed i an origin specific manner
if a gene inherited from the father is imprinted
it is silenced
in imprinting you inherit
one working copy
if the allele from the father is imprinted …
it is silenced and only the allele forms he mother is expressed
if the allele from eh mother is imprinted…
then only the allele from the father is expressed
what happens when one gene is imprinted (turned off) and the other is defective
DISEASE e.g. PW
imprinting (silencing of genes) is caused by
methylation within germ cells (eggs or sperm)
abnormality in which chromosome causes PW
15
Why will the phenotype of the offspring be normal
although the maternal gene is impritted (switched off by DNA methylation in the egg), only one copy of the functional gene is needed to be normal
Why will this individual have PW?
Only need one copy of the gene to have a normal pehnotyep. however here deletiosn within the chromsome has caused the paternal copy to be defected = gene deleted
In PW which allele is imprinted
maternal
rare geentic disorders cannot
explain popualtion variation in BMI
- down to a mixture of enironment and genes
when letpin is mutated
cant bind to its receptor on the orexigenic or anorexigenic pathway
–> therefore always seems low level-> causes activation of AGPR
when leptin recepor mutated
wont bind leptin
- increase hunger due to leptin decreasing hunger at high level
MC4R
chidlren get larger and talller
- more hungy
- more food absorbed and less excreted
- high fasting isnulin
POMC
when mutated it stops satition signals from being sent
- oxregigenic pathway stays stimulated
which part of the brain controls hunger
hypothalic arcuate nuceleus
obese patients are
leptin resistant
decrease in fat- e.g. when hungry
decrease in leptin
- less leptin bounds to its leptin receptor
- stimulates release of particular NT e.g. AgPR
- AgPR stimulates the orexigenic pathway
- leptin also inhibts POMC receptors- reducing amount of MSH released
- Inhibiting MSH release keeps us from feeling full
increase in fat after meal
- increase in leptin
- stimulates anorexigenic pathway
- when leptin receptor not stimulated, AgRP not released, inhibiting appetite
- increase i leptin stimulates POMC neurones, increasing the amount of MSH released- tells us we are full
