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  #1  
Old 01-04-2011
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DNA Prader Willi vs Angelman syndrome

I have a major confusion about the difference between the two..

I will narrate what I understand and can any one of u kindly correct me where I am wrong..both the disorders occur on chromosome 15..maternal chromosome normally has an imprinted Angelman gene and an active Prader Willi and vice versa for the paternal chromosome..now Prader Willi occurs when the paternal chromosome is deleted in which case the maternal chromosome which has the imprinted Prader wiLli gene and the active Angelman gene survives..so shouldn't the person have Angelman syndrome instead of Prader Willi??

would b grateful if someone clarifies my doubt

thanks in advance!
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  #2  
Old 01-05-2011
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Arrow Simply like this ...

You and I have two copies of chromosome 15.
One that came from our mom and the other came from our dad.

In a specific area of the chromosome namely 15q11-13 the gene is under what's called imprinting. Which means the maternal copy express proteins different from what the paternal copy express.

So if you lose your paternal copy you'll get Prader Willi and if you lose your maternal copy you'll get Angelman syndrome.
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  #3  
Old 01-05-2011
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Yes, what was said above is correct, lemme offer an even simpler explanation going deeper into genetics.

Due to genomic imprinting, offspring will show different phenotypic variations, now what variations are expressed is key to what phenotype you will show, what imprinting basically is that during gametogenesis 1 gene (out of a pair of genes from mother and father, 1 from each) will be turned off by methylation, now what you will express depends on which one of the genes is turned off and which is expressed, gene from the mother can be active and father's gene can be turned off or vice versa.

In these 2 diseases that you mentioned there is interstitial chromosomal deletions on Ch 15 (again remember you have a pair of genes, 1 from father, 1 from mother). In the case of PW syndrome, father's gene is the one which is active thus you don't get PW, so if there is a deletion in that gene you automatically know that the mother's gene is already turned off, thus manifestation of PW with Mental Retardation, hyperphagia, obesity, hypogonadism and hypotonia.

In the case of Angelman's syndrome the deletion and activity of gene is opposite (mother's works, father's doesn't) so the working gene (mom's) is deleted thus you end up with mental retardation, seizures, ataxia "happy puppet" like symptoms.

hope this helps

goodluck!
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  #4  
Old 01-06-2011
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Help

Quote:
Originally Posted by meka View Post
I have a major confusion about the difference between the two..I will narrate what I understand and can any one of u kindly correct me where I am wrong..both the disorders occur on chromosome 15..maternal chromosome normally has an imprinted Angelman gene and an active Prader Willi and vice versa for the paternal chromosome..now Prader Willi occurs when the paternal chromosome is deleted in which case the maternal chromosome which has the imprinted Prader wiLli gene and the active Angelman gene survives..so shouldn't the person have Angelman syndrome instead of Prader Willi??
First, I think that StepTaker's way (just memorise the pattern and remember that it's imprinting) is the easiest way - there's so much to learn for step 1 that the intricacies of epigenetic inheritance in human disease may not be the best use of our brain-space!

If that is unsatisfying, though... It seems like your confusion comes from whether it's gain-of-function or loss-of-function. As Kal-El was saying, both syndromes result from a loss of function.

For example, Angelman Syndrome:
- results from a loss of function of an ubiquitin ligase gene called UBE3A (the name of the gene doesn't matter). You need one working copy in your brain to be normal (i.e. not have Angelman syndrome)
- in the brain, this gene is normally silenced in the father and active in the mother
- deletion of the maternal 15q11-13 can result in Angelman syndrome because there is only one, silenced, copy (from the father).
- loss-of-function mutation in the maternal 15q11-13 can result in Angelman syndrome because there is only one, silenced, copy (from the father).
- paternal disomy at 15 can result in Angelman syndrome because there are two silenced copies.
- mutations in the imprinting center within that section (which codes for a ncRNA that normally silences an antisense transcript siRNA) can cause Angelman syndrome because the maternal allele is silenced like the paternal one.

In all those scenarios, there is no un-silenced copy of the allele to be expressed in the brain, and this results in the Angelman phenotype.
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  #5  
Old 01-06-2011
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All three explanations are pretty good - let me throw my hat into the ring as well:



One copy of the gene comes from the father, one copy from the mother.

In Prader Willi - the copy from the mother is silenced to begin with and there is a mutation in the copy from the father - this leads to loss of function and Prader Willi

In Angelman - the copy from the father is silenced and there is a mutation in the copy from the mother - leading to a loss of function and Angelman

Does that sound about right?
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  #6  
Old 01-06-2011
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Default again confusion

Quote:
Originally Posted by Mondoshawan View Post
First, I think that StepTaker's way (just memorise the pattern and remember that it's imprinting) is the easiest way - there's so much to learn for step 1 that the intricacies of epigenetic inheritance in human disease may not be the best use of our brain-space!

If that is unsatisfying, though... It seems like your confusion comes from whether it's gain-of-function or loss-of-function. As Kal-El was saying, both syndromes result from a loss of function.

For example, Angelman Syndrome:
- results from a loss of function of an ubiquitin ligase gene called UBE3A (the name of the gene doesn't matter). You need one working copy in your brain to be normal (i.e. not have Angelman syndrome)
- in the brain, this gene is normally silenced in the father and active in the mother
- deletion of the maternal 15q11-13 can result in Angelman syndrome because there is only one, silenced, copy (from the father).
- loss-of-function mutation in the maternal 15q11-13 can result in Angelman syndrome because there is only one, silenced, copy (from the father).
- paternal disomy at 15 can result in Angelman syndrome because there are two silenced copies.
- mutations in the imprinting center within that section (which codes for a ncRNA that normally silences an antisense transcript siRNA) can cause Angelman syndrome because the maternal allele is silenced like the paternal one.

In all those scenarios, there is no un-silenced copy of the allele to be expressed in the brain, and this results in the Angelman phenotype.
oh my god.....
praderwilli syn-when paternal chrom.15 is deleted
angelmann syn-when maternal chrom.15 is deleted

but what do u mean by silencing...... silencing shud mean there is no function for that particular gene..but as i cud read it says praderwille syn paternal chrom. is deleted n maternal chrom. is silenced..?????
cud u xplain it again?????
__________________
shravya..
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  #7  
Old 01-06-2011
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thanks i think i get it now!
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Old 01-06-2011
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Quote:
Originally Posted by Dr.B.SHRAVYA View Post
oh my god.....
praderwilli syn-when paternal chrom.15 is deleted
angelmann syn-when maternal chrom.15 is deleted

but what do u mean by silencing...... silencing shud mean there is no function for that particular gene..but as i cud read it says praderwille syn paternal chrom. is deleted n maternal chrom. is silenced..?????
cud u xplain it again?????
Prader Wili and Angel man genes are two separate genes. yes both in the same chromosome region.



Paternal prader wili gene is active.
PWdad PWmom
Maternal angelman gene is active.
AMdad AMmom


You delete either of the green ones, you have loss of function..
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  #9  
Old 01-06-2011
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Both are microdeletion
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