Genome
imprinting is unique among mammals. It
is a phenomenon that a few genes are expressed according to their parental
origin. Imprinted genes facilitate us to
comprehend the intricacies of a particular lineage and prediction of behaviour
as well as human diseases. These genes
which are privileged to become transgenerational imprints are initiated through
gametogenesis, inherited by mature gametes and infused in the following
generation. As elaborated by Elizabeth
Pennisi (24), the age old mule breeders noticed that a mare crossed with a
donkey yields a mule, whereas a hinny resulted out of the cross between
stallion and donkey. These breeding
experiments gave insight to ponder over the phenomenon of paternal or maternal
imprint of characters among offspring i.e., ‘parent-specific effects’ in
offspring. In other words, the
characters from any one of the parents have preponderantly marked or imprinted
in the progeny.
There are
nearly 40 genes whose expression depends on their parents of origin. A few to mention here are: 1) Igf2r and 2)
H19 - they are active only when inherited from the maternal side and 3) Igf2
expresses only when inherited from father – all of which are invariably
influenced by epigenetic tags.
Furthermore, a number of disease causing genes also follow the pattern
of imprinting. They include necdin and UBE 3A genes present on
chromosome 15. They cause Prader –Willi and
Angelman syndromes respectively (24).
The tumor suppressor gene, p73, which is involved in the brain cancer
neuroblastema, also comes under this category.
It has also been shown that imprinted genes are clustered in specific
chromosomes. For e.g., H19, Igf2 and six other imprinted genes are
found in close proximity on human chromosome 11 (11p15.5). Another set of imprinted genes viz., DKK1 and
GTL2 spatially lie together on human chromosome 14 (14q3.2) arranged in the same
temporal order as found in mouse, which facilitates for reciprocal
expression. The enzyme viz., maintenance
DNA methylase (Dnmt1) possibly plays a crucial role in the sustenance of
genomic imprinting.
Thus, the
clustered maternally or paternally expressed imprinted genes with biased
methylation towards any one of the parental chromosomes would result in the
trans-generational expression of such genes reflecting the appearance of
corresponding trans-generational behaviour or phenotype. Moreover, the genomic imprinting confers a
developmental asymmetry on the parental genome through epigenetic preferences
on the cluster of genes in blast cells and embryo (25). The heritable epigenetic asymmetry regulates
one of the parental alleles clustered through specific cis-acting imprinting
centers. These modifications are
manifested in the germ line and inherited as imprinted alleles which would be
more graciously termed as epialleles.
Therefore, the mechanism of genomic imprinting serves as a model system
for the evaluation of epigenetic microenvironment on the schedule of awakening
of gene function.
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