Imprinting....elightenment <grin>

Graham Dellaire popa0206 at PO-Box.McGill.CA
Wed Jul 5 22:58:02 EST 1995

Nick wrote:

>I hope to have enlightened you, but should you wish more information, I highly recommend a reading 
>Argiris Efstratiadis' review in Current Opinion in Genetics and Development (1994) 4:265-280, as well 
>Rob Nicholls' editorial in Am. J. Hum. Genet. (1994) 54:733-740.


Thanks for the references... but the condescending tone whether ment directly or 
inavertently in "hope to enlighten you." seemed somewhat bitter <grin> for such an "elightened 
person as yourself.

Benefit of the doubt is given.

As per my first post prior to the 28th oif June which may be the first post you
read Nick was in response to a Med student who wanted a quick and dirty 
definition of imprinting.  I gave it to him.  Gene dosage is an easy concept...
replication timing as it pertains to disease is not.  Praderwillie/Angleman disease
is good example of imprinting at work in human disease but is far from it conceptual 
land mines and was therefore not a good start for someone. 

some Q.'s

you wrote:
>imprinting, in general, refers to the BEHAVIOR of a gene, depending on the sex of the parent	
>which transmits it. 

Behaviour is pretty ambiguous.
You gave 
-replication timing
-differential methylation
-severity/age of onset of certain human disorders

so gene expression(timing and tissue specificity) was ommited.... is this not a "behaviour" of a gene?

hmmm. how is replication involved in disease?  If it is in the reviews don't bother posting it, I will
read it in its entirety rather than have you waste time paraphrasing it <grin>.

okay differential methylation is the classic paradigm (perhaps involving replication timing too...
there is work at McGill (in exp. Medicine actually in Maria Hadjopolos's (spell)  lab I think) that has 
some interesting evidence that replication timing may involve some sort of methylation which is
imprinted....EEK!   excuse me if I lack the details it is late and I can't find my notes from the 
Exp. Med. Lecture Day <grin>.  Aren't highly transcribed genes usually associated with early
replicating DNA...  therefore perhaps replication timing is a reflection of the transcription state
of the DNA and then this of course may reflect on gene dosage <grin> again.

I am in no way endorsing methylation as the imprinting "cure all"  but it is a damn interesting 
phenomenon in itself.

severity/age of onset... hmm this is multi-factorial I think (diabetes comes to mind) involving many
genes and gene products.  and ummm how does severity relate to imprinting ?  Dosage may be
involved conceivably couldn't it?

Lots of interesting tidbits where clipped as they do not pertain to the discussion as to 
whether gene dosage is a good model to help someone "start" thinking about imprinting.
I thought it was.  I received a few complements from people apparently less "enlightened"
for distilling some of the gobbly gook and disjointed thoughts down to a simple concept to
hang on to.  

Imprinting is still a sticky subject!

I give the benefit of the doubt to you Nick as I think you just read one of the later posts
where we focussed on a small area of  the imprinting phenomenon (ie. dosage as related to X 
inactivation and "Xist" and trinucleotide repeats of which a great review was sighted).

You came in on a thread
that is  more than a week old.


P.S. Two bits appreciated quand meme : )
Good to see some more McGill people expressing themselves!
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