b2d6 at musicb.mcgill.ca
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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