It’s hard to believe that only some 60 odd years have gone
by since Watson and Crick introduced humanity to the double
helix.  Today, terms like genes, DNA, RNA, genetic mutations,
genetic (inherited) diseases and so on are common currency.  Most
of us know what they mean.  Indeed, the time came when the
scientific world asked itself the question:  Can we map the human
genome?  Can we determine what all the letters of this intriguing
universe are?

The human genome project began in 1990 and was initiated by
the U.S. Department of Energy and the National institutes of
Health.  My understanding is that this was a worldwide effort
with many countries entrusted with the task of decoding and
recording a part of the genome.  It was expected to take 15
years, instead it was completed in 13 years.  A rare example of a
project that finished ahead of time!

When the dust settled, the 3 billion chemical base pairs
that make up the human DNA were identified and stored in
databases to be used by the scientific world.  The result?  A
whole bunch of the 4 bases:  A,C,G,T (more on that in a
subsequent section).  The whole thing really was an endless
procession of these 4 letters.  It doesn’t make for exciting
reading unless you’re engaged in genetic research.

Ultimately, some 30,000 genes were identified (we expected
some 100,000 genes).  Only a small portion codes for proteins,
the rest was considered as “junk” DNA.

The project was extended to nonhuman organisms:  Human gut
bacterium Escherichia Coli, the fruit fly, and the laboratory
mouse.  I believe that the genetic coding for many more organisms
was subsequently mapped out.  All in all, a tremendous
achievement for humankind.

So was it time to crack open the champagne?  To be sure we
can and should celebrate as long as we keep in mind that a
tremendous amount of work is still left to identify and determine
the functions of the proteins coded by the genetic machinery.
This will take us decades if not centuries.  Fine, but then will
we have reached the summit of the mountain?  Not by a long shot!
Enter epigenetics.

I have heard of epigenetics some 25 years ago.  The term
itself has been around for close to a century.  Serious work was
carried out for some 30 years by a handful of scientists only.
Most of the scientific community scoffed at the notion that our
genetic destiny was not hardwired into our DNA.  (One of the
early pioneer, Dr. Moshe Szyf of McGill University in Montreal
likened epigenetics to software:  a gene could have as many as
700 epigenetic programs!)  During the last 8 years, however,
epigenetics is finally getting the attention it deserves; work is
carried out across the world.  For me this is great news, for I
have always been fascinated by the intriguing possibilities of
this area of science, but otherwise had little information to
satisfy my curiosity.  There is now more data on epigenetics,
enough to share some of it with you in this article.  (The
material for this writing, if you want to delve further, was
obtained by going on Google and entering:  Epigenetics, and
Epigenetics in Plants.  Needless to say, you can enter such
search terms as Epigenetics and Cancer, Epigenetics and
Addiction, and so on).

Keep in mind that this is only a bird’s eyeview of
epigenetics.  I would not want to vouch for the total accuracy of
what is presented.  I am simply sharing the fruits of my
research.  It is certainly incomplete; for example, there is so
much more to say on the connection between epigenetics,
lifestyles, and environment.  The point I am making is this:
Research further if a specific topic is of interest to you.

A few more points:  I did not attempt to break the subject
into clearly delineated sections; that would have been impossible
considering the complexity of the topic and the fact that this is
a new area of science.  Also, there is overlap and repetitions.
This after all is the presentation of the different facets of one
subject:  Epigenetics.

I have kept my article as simple as possible; I believe it’s
accessible to the average person.  Do not let big words such as
Methylation, Imprinting, Histones, Chromatin Structure, Silencing
of Genes, etc., scare you.  Everything is, I believe, simply
explained.  (If I can understand it and write about it with an
accounting background, so can you!)

I have included a part on the biological aspects of our
genome.  (The Dance of Life:  Sections IV, V, and VI)  Those of
you with a solid biology background will probably not need it.
On the other hand, those of you totally lacking such knowledge
may have difficulty following it.  It is fascinating, but it is
not essential to understand the rest of the article.  Therefore,
feel free to skip it.

Finally, I close the article by providing you with my own
assumptions.  It brings the whole thing down to earth.  I suspect
you will also have your own views on the subject.

With this introduction out of the way, I am explaining next
some essential concepts before moving on to the various parts.

Epigenetics literally means “on” genes.  It’s an area of
science that deals with all modifications to genes excluding
changes in the DNA sequence itself.  (When a cell divides, an
error could occur when transcribing the information to the
daughter cell; this is called a mutation and should not be
confused with epigenetics).  Epigenetics modifications include
addition of molecules, like methyl groups, to the DNA structure.
Adding these components changes the appearance and structure of
DNA, it will change how it relates to important transcribing
molecules in the cell’s nucleus.

Importance of Epigenetics

By nature, the genome is largely static; epigenetics
modifications on the other hand introduces a measure of
flexibility to the process; they provide a necessary dynamic
variability to cellular function and phenotype, allowing for
cellular differentiation.  Epigenetics may also play a role in
evolution, epigenetic modifications can be passed on to future
generations.  Often, however, these modifications are lost after
several generations.  (Contrast with genetic modifications which
do not disappear).

As will be pointed out (under Methylation and Histones),
epigenetic modifications, or “marks,” impact on how genes can
interact with the cell’s transcribing mechanism.  Marks can turn
genes on or off, allowing or preventing the genes from
synthesizing a protein.

Silencing of Genes

Picture a top management meeting in a given corporation.
The president, vice-presidents, and some key personnel are
meeting to discuss a difficult problem and hopefully find a
solution.  What is the most important thing that should be
observed during such a meeting?  Silence!  I don’t mean that
total silence should prevail, simply let the expert in a given
area express his views without interference.  When the vice-
president in charge of marketing speaks, there should be total
silence with everybody else carefully listening to what he has to
say.  I can see you smiling already, that doesn’t happen in real
life.  Even if the president has demanded total silence, nothing
stops the other attendees from going, in their own mind, in a
different direction.  Listening carefully?  Not a chance!  This
is contrary to human nature.  The body, however, cannot afford a
cacophony.

Silencing of genes is nature’s way of giving each cell a
complete set of genes, and having organs perform specific
functions.  With some 30,000 genes in the human genome, selective
silencing is critical.  The stomach cells that produce
hydrochloric acid should not be turned on in the brain!

This process is governed by epigenetics factors.
Methylation, the addition of a methyl group, plays a role in all
sort of phenomena in which genes are switched on or off, for
instance, the growth of cancerous tumors.  Hypermethylation can
interfere with tumor suppressor genes.  Such epimutations has
been observed in many cancers.  This open the way for the
treatment of some cancers.  We’re not there yet, but epigenetics
could provide us with a weapon to fight an implacable foe.

DNA methylation is the addition of a methyl group to
specific bases in the DNA sequence.  A methyl group includes 1
carbon atom + 3 hydrogen atoms (-CH3).

Startling scientific discoveries have recently revealed that
single nutrients, toxins, behaviors or environmental exposures
can silence or activate a gene without actually altering its
genetic makeup.

For instance, environmental exposure initiate a chemical
modification that mobilizes a methyl group.  In turn, the methyl
group attaches to the control segment of a gene and either
silences it or alternately activates it.  One way or the other,
the gene is compelled to change its normal activity

Methylation plays an important role in plants.  More will be
said on that in the section on plants.

Histones

The DNA is tightly wound around proteins known as histones.
When the time comes to transcribe the genetic information, the
cell needs to unwind its DNA in order to make it available to the
RNA.  Alterations to this structure cause certain genes to be, or
not to be, available to the cell’s chemical mechanism and thus
determine whether those genes are expressed or silenced.

As already noted, DNA methylation will do the same thing,
but presumably under different circumstances.

“Junk” DNA

When the human genome was mapped out, we discovered that we
differ from one another (regardless of environment, nationality,
or race) by a tiny fraction of 1%; I believe less than 1/10 of
1%!  A further blow to our ego is that we differ from chimpanzees
by about 2%!  But the biggest surprise was that only 2% of our
DNA – via RNA – codes for proteins; the rest was considered
“junk,” the leftover is the result of million of years of
evolution.

Now that epigenetics is becoming a bona fide science, with
more interest from the scientific community, scientists are
discovering that some of this junk DNA switches on RNA that may
do the work of proteins and interact with other genetic material.

Introducing Flexibility

The genes identified by the human genome project are now
widely viewed as a set of instructions for the human body.  But
genes themselves need instructions for what to do, and where and
when to do it.  Remember that genes in all the cells of a given
individual are identical.  Moreover, I explained that gene
silencing or activation is part of the operation; as well, I
pointed out that this process is part of the job description of
the epigenes.  And it’s a good thing!  Genes are largely cast in
stone, the epigenome (an array of chemical markers and switches),
lie along the length of the double helix.  These epigenetics
markers and switches turn on and off the expression of particular
genes.  They introduce needed flexibility to the genetic package.
Think of the genome as your computer, it’s hardwired, without
software it can do a limited number of tasks.  The epigenome on
the other hand is the software, it allows your genes to do so
much more (i.e. produce a variety of proteins, etc.).  It allows
you to adapt to various conditions and circumstances.  It
introduces flexibility to the human body.  (This point will be
made in many different ways in the coming parts.  By the time
you’re through, you’ll wonder how come science has been blind for
so long to this important biological phenomenon).

Sources

1) The U.S. Human Genome Project
www.ornl.gov/sci/techresources/2Human_Genome/project/about.shtml

2) How epigenetics shapes life
www.scienceinschool.org/2006/issue2/epigenetics/

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

4) Epigenetics:  The Science Of Change
www.ehponline.org/members/2006/114-3/focus.html

5) Importance of epigenetics
www.epidna.com

6) Epigenetics
A new science peels away another layer of the genetic onion
By John McManamy
www.mcmanweb.com/epigenetics.html

7) Duke University Medical Center (2005, October 27).
“Epigenetics” Means What We eat, How We Live And Love, Alters How
Our Genes Behave
www.sciencedaily.com/releases/2005/10/051026090636.htm

8) DNA Is Not Destiny
The new science of epigenetics rewrites the rules of disease,
heredity, and identity
By Ethan Watters
Published online November 22, 2006
http://discovermagazine.com/2006/nov/cover

9) It’s all in the epigenes
By Daniel Tencer
The Ottawa Citizen
August 26, 2006

DNA (Deoxyribonucleic Acid)

A DNA molecule is very long and very thin, yet it fits
inside a much smaller (cell) nucleus and is folded up in the
chromosome in a very precise manner.  DNA is a linear polymer
made out of four different building blocks, the nucleotides.  The
sequence of the nucleotides is in effect the genetic information
that will allow the cell to carry out its work.  Each nucleotide
is composed of three parts:  The first part is a nitrogenous base
known as Purine [Adenine (A) and Guanine (G)] or Pyrimidine
[Cytosine (C) and Thymine (T)]; the second part is a Sugar,
Deoxyribose; the final part is a Phosphate Group.  The
nitrogenous base provide any given nucleotide with its identity
and it is referred to by its base, i.e. A,C,G,T.  (This in effect
was the information provided by The Human Genome Project, an
endless number of A,C,G,T; billions of them!)  One DNA strand can
be up to several hundred million nucleotides in length.  Note
that T match with A and C with G.

Picture a technical setting with technicians assembling the
components of an intricate device.  They are guided in their work
by an instruction manual, it’s their bible.  This is in fact the
role of DNA inside the cell; it provides the cell with the
instruction it needs to do its work.  However, the “technician”
is RNA (Ribonucleic Acid); it translates the information into a
medium that can be used directly by the cell.

Note that all cells for a given individual contain the same
genetic information.  However, for any given organ, only certain
genes are expressed, the rest are silenced (they are inactive).
For example liver cells will only produce the proteins allocated
to the liver, not those of the heart or the brain!  This gene
silencing process has been discussed in the Overview.

RNA (Ribonucleic Acid)

RNA differs from DNA in that it includes in the second
position of the Ribose Ring a Hydroxy (-OH) group.  Put in a
simpler way, Thymine (T) does not occur in RNA and is replaced by
Uracil (U).  Thus the coding for RNA is A,C,G,U.

RNA has three functions: a) It serves as the messenger that
tell the cell (the ribosomes) what proteins to make [Messenger
RNA (mRNA)]; b) It’s part of the structure of the ribosome, the
protein/RNA complex that synthesizes proteins based on the coding
carried over by the mRNA [Ribosomal RNA (rRNA)]; and c) it
obtains the Amino Acids (AA) (the constituents of the proteins)
needed by the ribosome [since it transfers to the cell the needed
AA, it is called Transfer RNA (tRNA)].

Looking upon it in a more simplified way, the DNA provides
the mRNA with a “shopping list” of AA and instructions as to how
to put them together (like in a recipe where you first list the
needed ingredients, followed by the required methodology to cook
this particular dish).  The rRNA does the “cooking” after the
tRNA had obtained and transferred to the cell the needed AA.

The process gets too technical after that and goes beyond
the scope of this simplified narrative.  I am, however, including
one important point.

The required genetic information is transcribed from the DNA
to the mRNA.  This happens at a specific site on the DNA called a
promoter.  Each gene has its own promoter(s).  Transcription ends
at a terminator sequence on the DNA.  The transcripts can be
between 300 to 50,000 nucleotides long and contain the
instructions needed to make the protein in question.  Generally,
the transcripts need to be processed before they can be used as a
blueprint for a protein.  This is done by removing intervening
sequences (introns) in the genes.

Ribosomes are roughly-spherical bodies that are contained
within the cell.  They are very small and can be seen only under
the electron microscope.  They are formed from two subunits, one
being larger than the other.

Ribosomes are the factory where a given protein is
manufactured.  Put in a simple way:  the mRNA brings the
instructions needed to synthesize the protein; the Amino Acids
(AA) required for the protein are carried to the site by the
tRNA; finally, as already mentioned, rRNA is part of the
machinery (and part of the ribosome itself) that manufacture the
protein.

Protein Synthesis

Physically you are made out of countless proteins.  Your
tissues, your bones, your blood, your organs, your enzymes, your
hormones, even your thoughts and memories are presumably
proteins.  The majority of proteins (within the same gender) are
similar.  Some proteins, however, are peculiar to a given
individual; indeed no two individuals have the exact same
proteins, not even identical twins!  (Because of the impact of
the environment, and its effect on the epigenetic code, identical
twins are not 100% identical.  This will be discussed in the
section on identical twins).

As discussed, proteins are synthesized in the ribosome of
the cell.  The assembly, following the blueprint provided by the
DNA and transported to the ribosome by the mRNA involves:

1) Controlled formation of a peptide bond between two AA.
This operation is repeated many times as each AA in turn is added
to the polypeptide chain.

Remember that at the end of the section on RNA I mentioned
that the DNA instructions include promoters and terminators
sequences.  These sequences in effect indicate to the ribosome
where to start and at what point to stop.  At the end of the
process, the manufactured protein is released to be used by the
body.  This operation is repeated million of times with a balance
maintained throughout the whole organism!  One question remains,
however.  How does the cell codes for the various AA?

2) The code

A great deal of work was carried out to crack the code.
Ultimately, the research was done in test tubes!  When many
biologists expressed doubt as to whether such a system really
operated in living organisms, more work was done on viruses with
a single strand of RNA.  To make a long story short, the validity
of the code was eventually verified.  If interested, you can
research and read further the fascinating story behind one of the
most extraordinary achievements of the 20th century!

So what is the code?

Remember that the four bases for RNA are: A,C,G,U.  Also
keep in mind that there are 20 AA and that we need different
codes for each one.

One base is insufficient to code a single AA.  Pairs of
bases could be arranged in 16 different ways (AA, UU, UA, etc.).
But we are still short since we have 20 AA.  Triplets of bases,
on the other hand, can be arranged in 64 different ways, more
than enough to code for 20 AA.  Because of this coding
relationship, a triplet of bases is called a codon.  To add to
the complexity, each AA is coded by one or more (up to six)
codons.

Three of the 64 possible codons (UAA, UAG & UGA) have not
been found to code for any AA.  They act as chain terminators.
When the ribosome reaches them, the polypeptide chain is
completed and is released to carry out its function in the cell.

Some examples of the code together with the corresponding
AA:

AUG for Methionine; UCG for Tryptophan; UUU & UUC for
phenylalanine; UUA & UUG for Leucine; CUU, CUC, CUA & CUG for
Leucine; GGU, GGC, GGA & GGG for Glycine.

Note the following:

1 to 4 codons codes for the above AA.

Leucine is coded by 2 or 4 codons (in most cases, several
codons code for a single AA, and one codon may be “preferred” by
one organism, another by a different organism).

I said that three codons (UAA, UAG & UGA) act as chain
terminators; what indicates the starting point?  AUG is used for
that purpose when it is at the beginning; when it is within the
message being decoded it is used (as shown above) to code for
Methionine.

Most of the codons have been assigned as a result of studies
with E.Coli; there is evidence that the code is the same for all
organisms.

There are 20 AA.  They are in alphabetical order:

Alanine.  Arginine*.  Asparagine.  Aspartic Acid.  Cysteine.
Glutamic Acid.  Glutamine.  Glycine.  Histidine*.  Isoleucine*.
Leucine*.  Lysine*.  Methionine*.  Phenylalanine*.  Proline.
Serine.  Threonine*.  Tryptophan*.  Tyrosine.  Valine*.

The atoms in AA are:  hydrogen, carbon, nitrogen, oxygen,
and sulfur.

We need to understand AA structure and properties to be able
to understand protein structure and properties.  Even a small
relatively simple protein is made out and depend on the AA which
comprises it.

Humans can produce 10 of the 20 AA.  The others must be
present in our diet.  Failure to obtain enough of even 1 of the
10 essential AA (those we cannot make) will mean that the body
will break its own tissues to obtain that one AA!

Unlike fat and starch, humans do not store excess AA for
later use;  AA must be part of our daily diet.  [Compare with
glucose which is stored in the liver and muscles (in the form of
glycogen).  It would be handy if the same applied to AA!].

The essential AA are indicated by an * in the above list.
These AA must be in your diet.

Plants, of course, must be able to produce all the AA.
Humans though lacks the enzymes needed to synthesize all 20 AA.

Sources

1) Arizona State University
Center for Bioenergy & Photosynthesis
DNA, RNA and Protein Synthesis
http://photoscience.la.asu.edu/photosyn/courses/bio_343/lecture/DNA-RNA.html

2) University of Arizona
Department of Biochemistry and Molecular Biophysics
The Biology Project
The Chemistry of Amino Acids
September 30, 2003
www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

3) University of Texas Medical Branch
Cell Biology Graduate Program
What happens at the site of the ribosome?
http://cellbio.utmb.edu/CELLBIO/ribosome.htm

4) Biology
John W. Kimball
Tufts University
Addison-Wesley Publishing Company
April 1975

One in every 250 births will result in IT.  They start and
end their lives with the same genetic package, but as they grow,
differences in their environment will alter their appearance and
behavior.

If one member of an IT set committed a crime and, in error,
left samples (hair, blood, etc.) which can be used to determine
his DNA, it would still be impossible to determine the culprit,
their DNA being the same.  However, closer inspection at the
molecular level will reveal significant differences, and thus
will help identify who of the two is guilty.  You see, they may
be identical genetically, but not epigenetically.  Some genes
might be active in one twin but not the other.

Why the difference in gene activity (or inactivity)?
Biochemical fine tuning of the genome will determine which genes
are expressed or silenced.  This point has already been outlined
under Methylation.  I have also discussed the impact of Histones.
The conclusion here is that IT are not really identical.  They
start that way, but then diverge.  But the time they reach old
age, they are really very different individuals.

One more important issue:  IT are not fated to suffer from
the same genetically inherited disease(s).  Dr. Arturas Petronis
M.D., PhD, head of the Krembil Family Epigenetics laboratory at
the University of Toronto provides us with an example.  There is
a high occurrence of IT with Bipolar Disorder, but Dr. Petronis
explains that epigenetics may account for the 30 – 70% of cases
where only one twin has the illness.  While IT share the same
genome, their epigenome differs.  Moreover, whereas DNA variation
are permanent, epigenetics modifications are in a state of flux
and generally accumulate over time.  This may elucidate another
mystery, namely why Bipolar Disorder tends to appear at ages 20 -
30 and 45 – 50.  This is due to the major hormonal changes at
these ages which may in turn impact genes regulations … via
their epigenetic modifications.

The good news here is that epigenetic disorders can be
reversed making them inviting targets for new drugs.

Sources

1) Epigenetics
Science in School
How epigenetics shapes life
www.scienceinschool.org/2006/issue2/epigenetics/

2) Epigenetics
A new science peels away another layer of the genetic onion
by John McManamy
www.mcmanweb.com/epigenetics.html

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

Inherited diseases until now seemed inevitable.  Cancer,
cardiovascular diseases, or dementia were destined to happen to
you if one or more of these illnesses has been running in your
family for generations.  This so far has been the accepted
wisdom.  But is it true?  No, thanks to epigenetics we can
overcome these curses.  But how can it be accomplished?  While
epigenetics is opening the door to some amazing medicines and
treatments, the solution is decidedly low-tech!  It goes back to
mother’s advice:  Eat your vegetables, eat less meat, do not
smoke, do not drink to excess, take a gym membership, and
generally keep body and mind stimulated.  Your mom didn’t know
it, but in so doing, you are altering your genetic destiny!

For instance, the health benefits of a proper diet and
exercise will actually modify the expression of our DNA, such
monsters as kidney diseases and Alzheimer which are lurking
within our genes can be banished.  Put in a more direct way,
let’s stop looking in the direction of scientific labs, the cure
in many cases depend on what we eat and how active we are.  The
cure in other words is in our hands.

Cancers

Many researchers engaged in epigenetics research are
targeting cancer.  Dr. Peter Jones, Director of the University of
Southern California’s Norris Comprehensive Cancer Centre view the
evidence linking epigenetics processes with cancer as “extremely
compelling.”  The Chief of the Carcinogenesis Division of Japan’s
National Cancer Centre Research Institute, Dr. Toshikazu
Ushijima, points out that epigenetics processes are one of the
five most important factors in the cancer field, and they account
for one-third to one-half of all known genetic modifications.

Under “Imprinting and Diseases” an important point was made.
I am restating it here.

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 produced.  Along the same line, many oncogenes
(growth-promoting genes) originate with the father.  On occasion,
we can have a double whammy, both sets of genes can malfunction;
if the maternal copy of the oncogene loses its epigenetics marks
and is turned on as well, cell growth gets out of control.

In Johns Hopkins University, research is conducted to
understand the mechanism behind imprinting.  Hopefully, in time,
drugs or treatments will be developed to address the above
epigenetics errors.

Autoimmune Diseases

Malfunctions related to the epigenetics immune system can
occur, and can be reversed.  The research was published in the
November-December 2005 issue of the Journal of Proteome Research
by Nilamadhab Mishra, an Assistant Professor of Rheumatology at
the Wake Forest University School of Medicine, and his
colleagues.

The team has established a specific link between aberrant
histone modifications and mechanisms underlying Lupus-like
symptoms in mice; there is a drug in the research stage,
Trichostatin, that can reverse the abnormalities.  This medicine
appears to reset the aberrant histone changes by correcting
hypoacetylation at two histone sites.

One more example of this type of research.  Dr. Bruce
Richardson, Chief of the Rheumatology Section of the Ann Arbor
Veterans Affairs Medical Centre and a professor at the University
of Michigan Medical School reported that pharmaceuticals such as
the heartdrug Procainamide and the antihypertensive agent
Hydralazine cause Lupus in some people.  He demonstrated that
Lupus-like symptoms in mice exposed to these drugs is linked with
DNA methylation changes and interruption of signalling pathways
similar to those in people.

In 2003, Dr. Moshe Szyf, professor of Pharmacology, McGill
University, and Michael Meaney, Associate Director of Research,
Douglas Hospital, conducted an important experiment.

First they observed that young rats who received a healthy
dose of maternal licking and grooming (the human equivalent of
maternal care) as pups developed into much calmer adults.  Those
rats who were deprived at the onset of this rat-like maternal
affection were decidedly more stressed.  This, needless to say,
is not an earth-shaking discovery.  We have known for a long time
the importance of maternal care, and its lifetime impact on the
individual.

The question raised by Meaney was “why the change in
behavior?”  It seems that the maternal licking stimulate a
chemical change in the glucocortoid receptor in the brain, the
very mechanism that regulates the amount of stress hormone
released by the rat’s adrenal gland.  The less maternal affection
a young rat received, the more stress hormones it produced as an
adult.

Next, Szyf administered methionine, an essential amino acid,
to the brains of the calm rats, this impacted their respective
glucocortoid receptors and they, like their neglected cousins,
became nervous wrecks!

Similarly, the McGill team reduced the levels of the same
hormones in anxious rats by pharmacologically manipulating the
same gene that produces them.  These findings have profound
implications, they suggest that similar interactions could be
used to fight depression, schizophrenia, and other brain
disorders.

Dr. Arturas Petronis M.D., PhD, Head of the Krembil Family
Epigenetics Laboratory at the University of Toronto, throw some
light on a long-standing enigma.  While DNA changes are
permanent, epigenetics modifications are in a state of flux and
generally accumulate over time.  This may explain why bipolar
disorder tends to appear at age 20 – 30 and 45 – 50.  This is due
to major hormonal changes at these ages which may in turn impact
gene regulations … via their epigenetics modifications.

The good news here is that epigenetics disorders can be
reversed making them inviting targets for new drugs.
The Future

Gradually, the evidence is accumulating and it is showing
that many genes, diseases, and environmental substances are part
of the epigenetics equation.  However, we need much more work to
be done in this area before drawing firm conclusions about the
impact of epigenetics on diseases.

Potentially, more research on epigenetics can go a long way
in curing many human diseases.  Yet, investment in this area of
study remains minuscule compared to that devoted to traditional
genetics work.  But there is a light at the end of the tunnel.

In Europe, the Human Epigenome Project was officially
launched in 2003 by the Wellcome Trust Sanger Institute,
Epigenomics AG, and the Centre Nationale de Genotypage.  The
group’s work is on DNA methylation tied to chromosomes 6, 13, 20,
and 22.  They may soon be joined by organizations in Germany and
India where research will be carried out on chromosomes 21 and X.

It’s a beginning.  But the task is enormous.  A Human
Epigenome Project will be far more complex than a Human Genome
Project.  The sooner we start, the better.  Humanity, even in the
21st century, is still affected by many diseases.

Sources

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

2) Epigenetics:  The Science Of Change
www.ehponline.org/members/2006/114-3/focus.html

3) Epigenetics
A new science peels away another layer of the genetic onion
by John McManamy
www.mcmanweb.com/epigenetics.html

4) McGill Reporter
McGill blazes epigenetics trail
Freeing ourselves from genetic destiny
Neale McDevitt
www.mcgill.ca/reporter/38/16/genes/