For some genes, the addition of methyl groups to the DNA
structure is used to differentiate gene copies, i.e. which is
inherited from the mother and which comes from the father.  This
is known as imprinting.  The epigenetics marks, in addition to
serving as identifiers, will also tell the cell which copy to use
to make proteins.

What is Imprinting?

Imprinted genes do not follow traditional laws of Mendelian
genetics which view inheritance of trait as either dominant or
recessive.  In Mendelian genetics both parental copies have an
equal chance to contribute to the result.  In the case of an
imprinted gene copy, however, the cell uses either the father or
the mother to make the required protein.

Imprinting in genetics is not new.  However, its impact is
gaining more attention as it is linked to more diseases.
Centuries ago, mule breeders in Iraq noted that crossing a male
horse with a female donkey produced a different animal than
breeding a female horse and a male donkey.

Further research on mice in the mid ’80s indicated that
normal development requires genes to be inherited from both
parents.  The research also indicated that the resulting
abnormalities changed depending upon whether the genes were from
the male or the female mouse.

The first naturally occurring example of an imprinted gene
that was discovered is the IGF-2 gene in mice in 1991; presently
about 50 imprinted genes have been identified in mice and humans.

Importance of Imprinting

It’s a bit of a mystery as to why imprinting evolved.  One
theory is that imprinting represents a genetic “battle of the
sexes,” since many imprinted genes play a role in embryonic
growth.

Simply stated, the male has a stake in growth and paternally
expressed genes usually stimulate growth; on the other hand,
maternally expressed imprinted genes (for which the copy from the
female is always used) suppress growth.  So what is at stake
here?  The male wants to pass on his genes, continuity is the
issue.  The female, however, is more interested in maintaining
her own health (in a biological sense) and therefore she opposes
the male genes and limit the size of the fetus.

Imprinting and Diseases

If we continue with the above theory, we find that imprinted
genes may have something to do with the development of cancer,
and other conditions in which tissue growth are abnormal.
Imprinted genes in which the mother’s copy is turned on usually
suppress growth, while the father’s copy usually stimulates
growth.

In cancer, some tumor suppressor genes that come from the
mother are turned off in error, and the growth-limiting protein
can no longer be synthesized.  Likewise, many oncogenes (growth-
promoting genes) originate with the father.  Sometimes, both sets
of genes can malfunction; if the maternal copy of the oncogene
loses its epigenetic marks and is turned on as well, cell growth
gets out of control.

There are birth defects collectively known as Beckwith-
Wiedemann syndrome; in this case, abnormal epigenetics leads to
abnormal growth of tissues, enlargement of abdominal organs, low
blood sugar at birth, and cancer.  Similarly, in the imprinting
disorder known as Prader-Willi syndrome, abnormal epigenetics
causes short stature, mental retardation, and other problems.

Causes of Imprinting Errors

When DNA copies itself, mutations (errors in copying) can
result, and the daughter copy will be somewhat different.  By the
same token, changes in a cell’s epigenetics can happen.  While
mutations are fairly well understood, causes of epigenetics
mistakes are less clear.  Scientists are aware that epigenetics
changes can be caused by environmental changes, but the details
are still hazy.

Imprinting Research

It’s important to carry out more research in this area.  For
example, what marks distinguish maternal and paternal gene
copies, and are they the same for all imprinted genes?  Can we
control the process and reestablish normal control to cells in
tumors?

Hopkins researchers created a mouse model in which the
paternal and maternal gene copies are easily distinguished; this
will help pierce the many mysteries connected with imprinting.
Equivalent experiments with humans are not currently permitted.

Source

Backgrounder:  Epigenetics and Imprinted Genes
www.hopkinsmedicine.org/press/2002/november/epigenetics.htm

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