Genomic Imprinting

Nick Giannoukakis b2d6 at
Tue Jul 4 21:31:26 EST 1995

For all those of you interested in the phenomenon of genomic imprinting:		

It is NOT simply a gene dosage effect, and it is NOT only confined to the parent-of-origin-dependent	
expression of a gene. Although this is the functional end-point  in certain cases (e.g. IGF2, H19, SNRPN 
and others), imprinting, in general, refers to the BEHAVIOR of a gene, depending on the sex of the parent	
which transmits it. 

This behavior can be in the form of replication asynchrony (e.g. igf2/H19 as well as a region within the 
Prader-Willi/Angelman syndrome locus),

Differential methylation of chromosomal regions (either accompanied by parent-of-origin-dependent gene
expression or not)

and the severity/age-of-onset of certain human disorders.

When refering to parent-of-origin gene expression and DNA methylation, imprinting has been shown to be a 
tissue-specific as well as a developmental-stage-specific phenomenon. It is also a polymorphic trait among 

Regarding X-chromosome inactivation, there are instances where a parent-of-origin-dependent inactivation 
occurs: this is in the extraembryonic tissues of mice, for example, and could conceivably occur due to a 
germline-dependent marking of the chromosome..

That certain diseases characterised by expanding trinucleotide repeats show an earlier age-of-onset and 
severity depending on the sex of the affected parent,  in my opinion, is not a good example to define 
imprinting. Other mechanisms may be at play in these cases.

The best examples, to date, are the Prader-Willi/Angelman Syndromes. They both map to the same 
chromosomal region (15q11-13), and both arise (usually) as a consequence of deletions within this region. 
When the deletion is of PATERNAL origin, the patient suffers from the Prader-Willi syndrome, a dysmorphic 
syndrome characterised by obesity, hypotonia and mental retardation. When the deletion is inherited from 
the MOTHER, it is the Angelman Syndrome which arises in the patient. Once again, this syndrome is 
characterised by mental retardation. This time, however, the patient is hyperactive and constantly laughs.

Although the deletions occur in a common region, molecular studies indicate that the genes responsible are 
distinct. Indeed, there have been a number of genes cloned from the Prader-Willi critical region which are 
expressed only from the paternally-derived allele. No such genes have been cloned from the Angelman 
region, BUT, there is a small area, recently defined, that may harbor such genes. It is anticipated that this   
(these) genes will be expressed only from the maternally-derived allele.

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.

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