Imprinting....elightenment <grin>

Nick Giannoukakis b2d6 at musicb.mcgill.ca
Thu Jul 6 10:55:14 EST 1995


Hello Graham,     

First of all, yes I did come in late on the thread of the discussion.
Second, I did not wish to be condescending in any manner, my posting was
in no way designed to flame. Being very intimate with the field, I felt
that some clarification needed to be made. Your example about gene dosage
is appropriate to explain the phenomenon at the functional level, but we
are not sure that this is always the case. My apologies to those who may
have been offended.

The term "behavior" is not ambiguous. In fact it encompasses all the
possible parent-of-origin-dependent phenomena. I feel that it is a more
appropriate term to use, rather than referring to gene expression, which,
as I indicated in my previous post, is in certain cases, the functional
end-point. We cannot assume that EVERY imprinted gene will act this way,
at the transcriptional level.

In fact, diabetes (type I) is transmitted preferentially from fathers to
affected offspring, and two of the recently mapped susceptibility loci
contain imprinted genes (11p15 and 6q25-27; IGF2 and IGF2R, fascinating,
no?).


How imprinted genes affect the age-at-onset and severity of certain
diseases is at present not known, so any hypotheses would be welcome. You
are right in surmising that the expression levels of the genes involved
would play a role, but, again, this would be the functional end-point.
Something must have gone wrong either at the stage where the imprint was
established, in the interpretation of the imprint, functionally,
post-fertilisation, or both.

Regarding replication asynchrony, instead of me wasting bandwidth,
Nicholls' review  should be a starting point to answer your question.

And, yes, I wholeheartedly agree that McGill should dominate the Internet!
Now, what about those impending fees........



                                          Nick.

























In article <3tfn0a$7pj at sifon.cc.mcgill.ca>, Graham Dellaire
<popa0206 at PO-Box.McGill.CA> wrote:

> Nick wrote:
> 
> >I hope to have enlightened you, but should you wish more information, I
highly recommend a reading 
> >of 
> >Argiris Efstratiadis' review in Current Opinion in Genetics and
Development (1994) 4:265-280, as well 
> >as 
> >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.
> 
> Graham  
> 
> P.S. Two bits appreciated quand meme : )
> Good to see some more McGill people expressing themselves!
> _______________________________________________________________________ 
> Graham Dellaire                     Snail Mail:
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> McGill University                   Montreal Blood Services             
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> Div. of Experimental Medicine       Montreal, QC, Canada           
> E-mail: popa0206 at po-box.mcgill.ca   H1W 1B2                        
> B2XE at musicb.mcgill.ca                                                      
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