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Epigenetics

Epigenetics

Epigenetics is a topic that absolutely fascinates me. If I had to give an extremely short description I would explain epigenetics as the grammar in a book with the DNA being the text.The name epigenetics means “on top of” but if you think this makes the study of epigenetics more important than the study of DNA then perhaps an example of text with and without grammar will make things clearer.From Arthur Schopenhauer, Counsels and Maxims, 1851:
Without grammar:“In this world where the game is played with loaded dice a man must have a temper of iron with armor proof to the blows of fate and weapons to make his way against men Life is one long battle we have to fight at every step and Voltaire very rightly says that if we succeed it is at the point of the sword and we die with the weapon in our hand”
With grammar:“In this world, where the game is played with loaded dice, a man must have a temper of iron, with armor proof to the blows of fate, and weapons to make his way against men.Life is one long battle; we have to fight at every step;and Voltaire very rightly says that if we succeed, it is at the point of the sword, and we die with the weapon in our hand.”
I wouldn’t be surprised if reading the first version was stressful. The second version illustrates the importance of grammar AKA epigenetics. It goes without saying that the grammar has no purpose without the text. Neither is more important.At this point we can move away from the vague rhetoric into the more technical aspects.
Dictionary.com defines epigenetics as;”Genetics. the study of the process by which genetic information is translated into the substance and behavior of an organism: specifically, the study of the way in which the expression of heritable traits is modified by environmental influences or other mechanisms without a change to the DNA sequence.
Yay it’s clear as mud! Basically epigenetics determines which parts of our DNA are active or switched “on” as well as acting like a volume dial to determine how active a particular gene is. Different aspects in our lives can alter these epigenetic markers; nutrition, drugs (prescription or otherwise), exercise, ect… can all increase or decrease gene expression (volume dial).Without getting super technical our DNA is wound up on special little spools. Whichever genes and their epigenetic markers are on the outside, are the ones we can alter with lifestyle choices. The segments of DNA (and markers) that are not accessible is what we can’t change, eye colour for example.For the visual learners:

Up until the 1950’s the term “epigenetics” was used in a much looser fashion compared with today’s definition. The word was used to refer to all of the developmental events that went into an organism from fertilized egg to maturity. Now it refers to the changeable markers that turn a gene on or off, and how “loud” that gene will be.The original definition began with studies in embryology and cell biology that started in the late 19th century (1800’s). These studies would lay the groundwork for our current understanding between development and our genes.There was a long standing debate among embryologists that through a series of complex experiments, divided them into 2 schools of thought. The first felt that cells had pre-formed elements that got larger as the fetus grew, aka your eyeballs came from cells that had tiny eyeballs that grew bigger and merged into your fully formed eyeball before birth. That is a bit oversimplified but you get the idea (PUN!).And the second believed the developmental process actually involved a bunch of chemical reactions that executed a complex developmental plan. Both were a little bit correct. On one hand every single cell contains our full DNA sequence, which means the information needed to form your liver, or skin, or nipples, is contained in the same cells found in the previously mentioned eyeballs. And on the other hand interactions between proteins determines which parts of the DNA sequence are activated to allow the basic stem cells turn into eyeballs, liver, or skin, instead of something else.
One of the important processes in epigenetic expression is called methylation, this process is essential to all major systems in the body. Methylation is when the body transfers a methyl group (1 carbon and 3 hydrogen) from one substance to another in the body.Certain nutrients are essential to this process, folate in particular is crucial. Folate comes from our diets (beans, spinach, asparagus, liver) or supplements. Once we have taken it in, our bodies must convert it into an active form (methylfolate) to use it.Up to 60% of the North American population have a gene mutation that alters how effective their bodies can do the process of methylation. These gene mutations fall under the shortened name of MTHFR, I personally like to call it the “motherfucker” gene because the effects on health can range from very mild to debilitating.A simple DNA test can tell you if you have any of the MTHFR gene mutations which allows you to research further and take an active approach to your health.
Genomic imprinting is another process associated with epigentics. Genomic imprinting specifically looks at which parent contributed a particular gene. A gene that has been imprinted is turned off. The reason this matters is because the source of a gene can in some cases determine whether or not a gene is expressed. For example on chromosome 15 we have a gene labelled UBE3A, if this gene comes from the mother the gene will normally be “on”, but if it comes from the father it will normally be imprinted, aka turned “off” in the brain, elsewhere in the body both copies are active. If the maternal copy has been imprinted by mistake in the brain, the offspring is born with Angelman syndrome. Prader-Willi syndrome occurs when the paternal copy of the chromosome is improperly imprinted or the offspring inherited 2 copies of the chromosome from the mother. A different set of genes is associated with Prader-Willi than Angelman.Deletions and mutations in genes is more common than improperly imprinted genes when it comes to genetic diseases.At this time researchers have identified roughly 80 human genes that can be imprinted, however research in other species such as mice, suggest that many more genes could be subject to imprinting. Mice have 600 different genes that can undergo imprinting.
When it comes to disease and epigenetics one of the most extensively studied links is cancer. The evidence in the research is globally considered to be “extremely compelling”, strong words from soft spoken people.Other disease links include Lupus and Lupus like symptoms and immune system effects, which means it is possible to reverse or minimise effects of the disease through lifestyle modifications to change the epigenetic expression.
As you saw in the video above most epigentic markers do not pass on, however some do and current research suggests these markers may persist up to 4 generations. A study was done in pregnant rats who were exposed to an insecticide and a fungicide that made 90% of the male pups infertile. No additional exposures were done but the infertility rate continued in subsequent generations. At this time additional studies have not been completed to my knowledge, the significance of the findings cannot be dismissed at this stage however. Over the course of our lifespans the lifestyle choices we make continually influence changes in our epigenomes, very little is set in stone. For mothers, the health choices we make for ourselves during pregnancy can set the stage for future generations as well as the one we carry. Another sex based difference can be found in what I call the “influence points”, that is, where in a child’s developmental timeline will environmental influences determine which epigenetic markers are most likely to be passed to future generations.For boys it appears to be during puberty, this is when the sperm cells develop. Based on the Swiss village mentioned in the video above it can be wise to physically push adolescent boys to be physically active and avoid over feeding.For girls the “influence point” is when she is still in her mother’s womb. That is when the eggs are developed, nutrition, stress, and exposure to toxic substances; all will have an effect that has a greater chance of being passed on.Regardless of “influence points” any pregnant woman is wise to aim for the best nutrition and appropriate physical activity level for her own health and the health of that individual child before thinking of future generations.In all cases having an attentive caregiver also influences epigenetic markers and overall temperament based on studies in rats. For humans we know attentiveness will influence brain development but we don’t yet know how it effects gene expression.The above statements are made only to highlight the important role each of us plays in creating the future.
There is global effort to research epigenetic influences and effects for every one of the 22,000 human genes. New technologies for measuring and analysing the data are being developed and schools are building courses for graduate students.Many scientists in the field of epigenetic research started in other fields such as cancer research, there is no single field represented which makes epigenetic research kinda like the wild west of science today.

Research materials:

https://www.whatisepigenetics.com/fundamentals/

http://learn.genetics.utah.edu/content/epigenetics/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392256/

Biology of Belief – by Bruce Lipton

What is Epigenetics? with Nessa Carey

Genetics, Epigenetics & Neuroscience Sages & Scientists Symposium 2016

Genetics, epigenetics and disease

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