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BTD Forums  /  Journal Club and Literature Review  /  Environmental epigenetics:
Posted by: Lloyd, Tuesday, July 30, 2013, 4:24pm
From reading material for an epigenetics course.

Environmental epigenetics: prospects for studying epigenetic mediation of exposure–response relationships
Victoria K. Cortessis,1 Duncan C. Thomas,corresponding author2 A. Joan Levine,1 Carrie V. Breton,3 Thomas M. Mack,1 Kimberly D. Siegmund,3 Robert W. Haile,1 and Peter W. Laird4

Quoted Text
Noteworthy experimental results, taken together, indicate that epigenetic processes could plausibly mediate effects of environmental exposures to influence disease susceptibility in mammals, since (1) specific exposures induced measurable changes in epigenetic state, (2) new epigenetic state was shown to persist after cessation of exposure, and (3) measureable phenotype was associated with exposure-related changes in epigenetic state. A fourth element, exposure-induced alteration of epigenetic marks of germ cell lineage DNA, seems necessary for transgenerational transmission of environmentally induced epigenetic changes. On this background, we interpret observational human data illustrating associations of exposures to epigenetic state and epigenetic state to disease to indicate that epigenetic mechanisms may plausibly mediate exposure effects on a wide range of human diseases.

Perhaps the greatest significance of this line of research is the potential for designing novel interventions articulated by Dolinoy and Jirtle (2008):

    unlike genetic mutations, epigenetic profiles are potentially reversible. Therefore, epigenetic approaches for prevention and treatment, such as nutritional supplementation and/or pharmaceutical therapies may be developed to counteract negative epigenomic profiles.

As an example, Huang et al. (2012) have developed a therapy for reactivating the Ube3a allele that is epigenetically silenced in Angelman syndrome. However, before we begin to realize this translational potential, much research along parallel tracks needs to be conducted.

We need to better understand basic epigenetic mechanisms that operate during selected periods when the epigenome may be particularly vulnerable to environmental exposures (e.g., prenatal and early postnatal periods, childhood, puberty) as well as mechanisms that routinely maintain proper epigenetic states. We also need to understand mechanisms relevant to cumulative effects of exposure and associations with aging, since duration of exposure and aging are co-linear. A better understanding of basic mechanisms at different time points in life would guide genetic epidemiology studies in selecting environmental exposures that are more likely to affect epigenetic processes, identify the most relevant periods of exposure, identify biomarkers of exposure, and suggest biological intermediates to study.

It may be helpful to more deliberately deconstruct the steps whereby an environmental exposure may affect risk of disease via epigenetic mechanisms. For example, studies of the association of environmental exposures with selected epigenetic events as endpoints (rather than intermediates in a complex pathway) may be fruitful and will likely help us better conceive of studies to elucidate an entire pathway, from an exposure acting at least in part through epigenetic mechanisms to disease risk.

As we proceed, it will be important to consider seriously the environmental exposures to study, since we will want to select the most promising candidate exposures (those most likely to affect epigenetic processes), measuring these exposures at relevant time periods and with reasonable accuracy. Also, we cannot ignore genetic influences on epigenetic processes. We see above that studies of the epigenetic state of specific candidate genes are yielding interesting results and more such studies are warranted. Given limited knowledge of this genetic–epigenetic interface, to complement the candidate gene approach, integrative genomics approaches should be contemplated in order to combine GWAS data with epigenomic data. Clearly, statistical and bioinformatics approaches will be required to enable the efficient conduct of these analyses, especially as we expand to genome-wide scale. Similarly, research on feasible, efficient study designs, akin to current research on optimum designs for sequencing-based studies, will be needed. Finally, as with other emerging fields (e.g., the standardization of testing criteria for microsatellite instability or MSI), standardization of terminology and testing protocols will facilitate future communication of hypotheses, scientific approaches, and results.
Posted by: Lola, Wednesday, July 31, 2013, 1:37am; Reply: 1
swami rules! ;)
Posted by: Amazone I., Wednesday, July 31, 2013, 8:38am; Reply: 2
weew thanx for sharing Lloyd :D :K)(smarty)(ok)(clap) I wanted to have this in script form but saw... 1 from  1592 sheets... and then up from sheet 17 american size and swiss size weren't anymore compatible ;) ;D.. woahoa.. ok so far I still will try to read the whole text ! Another thank you for this (book2)(hehe)(dance)
Posted by: yaeli, Wednesday, July 31, 2013, 9:36am; Reply: 3

You may have this printed out on a printer which has a driver with custom scale print option.
Posted by: Amazone I., Wednesday, July 31, 2013, 11:10am; Reply: 4
:K) :D ;D(clap)(ok)(dance)(smarty)
Posted by: yaeli, Wednesday, July 31, 2013, 11:37am; Reply: 5
:K) :K)
Posted by: Spring, Wednesday, July 31, 2013, 5:30pm; Reply: 6
Quoted from Lola
swami rules! ;)

Posted by: Averno, Wednesday, July 31, 2013, 8:18pm; Reply: 7

Wow!  From fringe to mainstream in the blink of a decade!   (woot)
Posted by: Goldie, Wednesday, July 31, 2013, 11:11pm; Reply: 8
Quoted Text
We also need to understand mechanisms relevant to cumulative effects of exposure and associations with aging, since duration of exposure and aging are co-linear.

Ok this I understood clearly /// the rest.... Interpret for those who are less versed... someone have mercy...

But indeed interesting... I would take my own experience with diabetes as an example... my father developed diabetes at some time in his life... sorry I have no idea when, my Brother di at maybe 40 plus.. I had the gen showing before anyone even thought of genes age 19 but did not develop it until way late in my 50ties.  The differences where lifestyle in the three of us...

It makes me wonder what a study of all who come here would look like... just in terms of money spent on doctors befoe BTD or a year after adhering to its core principals, and a measure or self reported pain scale, wellbeing scale from 1 to 10... !

The potentiality of THE (great) differences might be staggering.
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