“Understanding the Impact of Epigenetics” podcast

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by Shea Robison (@EpigeneticsGuy)

Understanding the Impact of Epigenetics podcast

Below are links to posts and papers I mention in this podcast about epigenetics and health that I participated in as a panel member hosted by the health and fitness website BreakingMuscle.com:

When it Comes to Epigenetics, How Much Fun is Too Much? Comment and Reply

Epigenetics By Any Other Name? What Epigenetics Should and Should Not Be

Epigenetics and Drug Discovery: The Missing Link?

Gene Sequence but not Structure? The Costs of Excluding Epigenetics from Genomics

Ben Laufer Comments on “Gene Sequence but not Structure”

Epigenetics Minority Report Part I: Epigenetics, blame, precrime and politics

All of these posts have many links to other posts on this blog and to external materials about epigenetics so click on these links for supplemental information. You can also navigate through the posts about the different topics I discuss on this blog using the pages in the header above or the Categories list located on the righthand margin of this blog.

Below is a link to a PowerPoint presentation in which I discuss the Agouti mice experiments and the longitudinal studies in humans that I mention in the podcast:

Agout Mice 2

Epigenetics PowerPoint

The link below is to the paper on the emerging narratives of epigenetics in regards to obesity that I reference in the podcast, which I presented at the 2014 annual conference of the Association of Politics and the Life Sciences:

The Emerging Obesity Policy Narratives of Epigenetics

I have also summarized a number of research papers on epigenetics. You can find these research summaries here:

Reasearch Summaries

Additional Information:

For a visual of how epigenetics work, you can watch this video from the University of Utah Genetic Science Learning Center.

Also, in this video:

a world class epigeneticist explains some of the mechanisms of epigenetics, as well as discusses some of the intriguing possibilities (video from the RWJF).

You’ve come this far, so I am curious about what brought you here. Read the posts that interest you, leave a comment or question, and let’s see what we can do.

Feel free to contact me at epigenetics.guy@gmail.com with any questions or comments.

Follow my epigenetics and policy themed Twitter feed @EpigeneticsGuy

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When it Comes to Epigenetics, How Much Fun is Too Much? Comment and Reply

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by Shea Robison (@EpigeneticsGuy)

This post began as a simple reply to a comment from Alison M to this post about epigenetics and drug discovery, but suddenly bloomed into a full-fledged post of its own. Below is Alison M’s original comment in italics for purely aesthetic purposes, followed by my reply (and I think Alison is actually responding to more than one post here, including this one about epigenetics as a possible bridge between the sciences):

TBH, I don’t think that combining the fields [genomics and epigenetics], at least at this point, would be beneficial to either. Both are still in discovery, and the known mechanisms of action of genetics and epigenetics are different enough that they might not ever be appropriately combined. Epigenetics needs to be better presented, especially to the public, so that it doesn’t fall prey so much to magical thinkers – not only for the sake of understanding, but also so that its legitimacy can be embraced by other scientific fields.

In this, some researchers do themselves no favors. Even Dr. Jirtle has some articles on his site that present ideas that look more like speculation than hypotheses. These are good for getting attention, but what I see among laypeople as a result is the wrong kind of attention. Bruce-Lipton-level wrong kind of attention.

Thanks to Alison M for taking the time to post her comments.

First, I definitely appreciate her point about both fields still being in discovery mode, and how the known mechanisms of both genetics and epigenetics are possibly different enough to defy unification even in the future when they have both ‘matured’ so to speak. However, one of the questions I still have about this integration of epigenetics and genetics is ‘But why not?’ (How is that for an emotional/unscientific reply? Having said that, I think I have more than merely emotional responses to support this question)

In this post and this post I discuss the first divergence of epigenetics and genetics in the 1920s, which had both scientific and less-than-scientific components to it, and in this post and this post I discuss some of the political (i.e., non-scientific) reasons for the subsequent…stigmatization (for lack of a better word) of epigenetics until fairly recently. My question through all of these posts is what if these circumstances were different during these  pivotal times?

Just as biological evolution can take many different trajectories depending upon initial conditions and random events (e.g., killer asteroids, etc.), so can the evolution of science. Given the influence of these non-scientific influences just mentioned, it is easy to imagine alternative circumstances in which epigenetics and genetics evolved together at this relatively early stage of both their developments such that today there are no disciplinary boundaries between what we call genetics and epigenetics as Dr. Jirtle proposes. Forgive my philosophyspeak for a moment, but there are no “ontologically objective”[1] reasons that genetics and epigenetics are mutually distinct fields; in fact, there would seem to be more reasons for them being unified than being distinct fields. However, given the path dependent nature of both biological and scientific evolution as discussed here, because these fields diverged when and how they did, epigenetics now represents some pretty fundamental challenges to genetics in both methods and conclusions (e.g., transgenerational inheritance). Again, though, there is no objective reason this should be—all we know is that this is the case now.

Finally, I wholeheartedly support the suggestion that epigenetics needs to be presented better than it currently is. The core of my dissertation—soon to be made Flesh, so stay tuned—is discussion and analysis of the different narratives of epigenetics that are emerging in major media outlets. I have posted elsewhere about the impact of epigenetics in the sciences and academia relative to the mass media for public consumption, as well as about some of the current misconstruals and misinterpretations of epigenetics amongst the general public, precisely because such misconstruals bring the wrong kind of attention and distract from what epigenetics actually is and does. In my professional career—and personally, because I am just fascinated by this stuff—I am concerned with the political implications of epigenetics both in terms of policies based on epigenetics as well as the internal and external dynamics of the science of epigenetics. This is why I also think more rigorous and sound presentation of epigenetics within the scientific community and to the general public is critically important—though by no means does the careful use of terms and definitions guarantee anything, as we can all think of instances of the misappropriation of genetics despite the best efforts of geneticists, from the insipid use of genetics, such as “DNA Love Connection?”[2] to the truly scary uses, such as the eugenics movements of the early 20th century.

To this end, @EpiExperts and @EpgntxEinstein recently recommended a very cogent commentary in the form of a review of an incredibly interesting-looking book[3] on this issue of the recent popularization of epigenetics (not to mention the blog post which kicked this whole thing off). While the author of the article proposes a definition of epigenetics that is perhaps too restrictive for my tastes, I still appreciate the effort to rein in the ‘Bruce-Liptonizing’ of epigenetics as Alison M wrote in her comment (and no offense intended to Bruce Lipton, whom I do not know and who I assume is a wonderful and well-intentioned and sincere person).

In the end, although I appreciate the almost intoxicating excitement that comes from witnessing the emergence of a field of research like epigenetics, at this point more caution in the description, interpretation and popularization of epigenetics is probably better than less…but hopefully not so much caution that it takes all the fun out of it.

[1] By which is meant phenomena which are ‘observer-independent’ (from Searle, John R. The construction of social reality. Simon and Schuster, 1995: 9-10)

[2] Special thanks to @AlexisCarere for bringing this gold mine of an example of genetics gone awry to my attention

[3] Weissmann G. (2012) Epigenetics in the Age of Twitter. Bellevue Literery, New York, NY.

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

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by Shea Robison (@EpigeneticsGuy)

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

Authors: Esther R. Berko, Masako Suzuki, Faygel Beren, et al.

Journal: PLosGenetics

Publication Date: May 29, 2014

This week’s paper deals with trying to trace the biological causes of Autism Spectrum Disorder (ASD). The authors begin by noting that one of the causes associated with ASD is the age of the mother, although the reasons for this increased risk are unknown. What is known is that the eggs of older women are more prone to chromosomal abnormalities, and so this has been suggested as a likely reason for this association between parental age and ASD. However, as the authors write, “age is also associated with a loss of control of epigenetic regulatory patterns that govern gene expression,” which suggests epigenetic dysregulation as a second potential mechanism. Thus, for this paper the authors tested both possibilities.

This effort to distinguish between genetic or epigenetic causes of ASD is the first reason for the selection of this paper as the paper of the week; the second reason is the extensive descriptions the authors give about the methods they use to test between these two mechanisms. For anyone interested in epigenetics, this discussion of the cutting edge of the technical side of epigenetics research can only be helpful.

Genetic mutations have long been proposed as the predominant cause for ASD, but the explanation of epigenetic mechanisms has recently gained credence as a cause for ASD. The authors cite three recent studies in particular which support epigenetic dysregulation as a potential mechanism in the incidence of ASD. A 2012 paper reported the discovery of distinctive chromatin features in the brains of subjects with ASD.[1] Authors of a paper published in 2013 tested blood leukocytes and found differences in DNA methylation between a monozygotic twin affected with ASD and their unaffected twin.[2] A second paper published in 2013 found differences in DNA methylation from subjects with ASD and subjects without ASD.[3]

Methods

To test whether ASD is the result of these genetic or epigenetic causes, the authors tested “homogeneous ectodermal cell types” from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years. Genome-wide tests were then performed on these cells to look for unusual chromosome numbers to test the hypothesis of genetic mutations; epigenome-wide analyses (EWASs) were used to test DNA methylation patterns in regards to the hypothesis of epigenetic dysregulation. This study, the authors note, “represents the largest epigenome-wide analysis to date testing a single cell type in ASD.”

The choice of this specific cell type served a couple of different purposes. First, the type of cell was selected because comes from the same developmental origin as brain cells. Second, the selection of this specific cell type minimizes the problem of “mixed cellularity” which has been already identified as a problem with EWASs.

The authors also addressed other such problems with EWASs, the biggest issue being “that the generally small changes in DNA methylation found may not be substantially in excess of the noise introduced by technical or biological effects influencing DNA methylation that have no relationship to the phenotype being tested.” To achieve what the authors call “the currently necessary level of stringency for EWAS studies,” the authors incorporated parallel SNP genotyping and “Surrogate Variable Analysis” (SVA) to account for these different possible sources of variability, as well as stringent pre-processing of the microarray data that was gathered and iterative use of this preprocessing data as means to focus in on only those regions of the DNA sequence that are being differentially methylated (i.e., to avoid ‘false positives’). Through these different efforts, the authors reduced the impact of these methodological issues due to “cell type and subpopulation heterogeneity, chromosomal aneuploidy, copy number variability, genetic polymorphism, age, sex and technical influences.” The authors go into considerable detail as to how these different approaches resolve these issues, so anyone interested should the relevant sections of the original paper.

Results

Using these rigorous and intensive methods to test the competing hypotheses of mutations in DNA versus epigenetic dysregulation as increasing the risk for ASD, the authors discover 15 differentially methylated regions (DMRs) at 14 genes which distinguished the ASD and TD samples. From subsequent analysis of these DMRs, the authors conclude that “DNA methylation patterns are dysregulated in ectodermal cells” in individuals with ASD, but did not find evidence of chromosomal abnormalities in those same DMRs. In their own words, the authors conclude that “of the two mechanisms we originally proposed for AMA causing ASD, covert aneuploidy occurring at detectable levels (≥20%) is not as likely to be involved as epigenetic dysregulation.”

Interestingly, though, the genes in these DMRs are those already associated with ASD, which means that instead of genetic mutations this analysis reveals “a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms.” In other words, the genes previously associated with ASD are still implicated in ASD, but through epigenetic dysregulation rather than through mutations in DNA sequences. However, the exact pathways of this epigenetic dysregulation are still unclear. Given the results of their study, the authors suggest aging parental gametes, environmental influences during embryogenesis, or mutations of the chromatin regulatory genes implicated in ASD as the most likely possible environmental factors in this epigenetic dysregulation.

Commentary

Some additional points of interest about this study are worth mention:

First, mosaicism in this context usually refers to differences in chromosomal makeup between cell populations within the same individual (the “covert aneuploidy” just mentioned). As this was not found to be significant, the “mosaicism” in the title of this paper refers not to chromosomal differences between cell types but rather “the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD.”

Second, the authors note prior epigenetic studies of ASD had used mixed cell types, which may have limited the ability to detect the effects found by the authors and their use of homogeneous ectodermal cell types.

Third, the authors note that their study implicated the same gene in epigenetic dysregulation (OR2L13) as found in two previous studies associated with altered DNA methylation in individuals with ASD. This replication suggests this gene is “especially labile in ASD in terms of DNA methylation and expression.”

Fourth, the authors observe that while the epigenetic changes they observed from a cohort of subjects born to mothers with AMA may be the result of the aging of the mother’s egg, the sperm of the fathers—who are likely as old as the mothers—may also be experiencing epigenetic changes of their own which are contributing to the epigenetic dysregulation observed in their study; as this was not controlled for in their study, subsequent efforts should include such controls.

Finally, given the ages of the parents and the increased probability of mutational events, the authors allow that the observed epigenetic dysregulation may actually be a secondary effect of the mutations in the genes involved, and not actually the cause but rather a symptom of ASD. What is most interesting to me about this suggestion is the authors’ recommendation that “combined genetic and epigenetic analyses of the same subjects will be needed to test these possibilities.” I have written about the substantial benefits of this combination of epigenetics and genomics before in terms of the need to identify the impacts of both gene sequence and three-dimensional structure on gene expression in general, and as it pertains to expanding the scope of disease phenotypes which are amenable to drug discovery in particular, and this paper provides yet another concrete example of the need to combine both epigenetics and genomics.

[1] Shulha HP, Cheung I, Whittle C, Wang J, Virgil D, et al. (2012) Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons. Arch Gen Psychiatry 69: 314-324.

[2] Wong CC, Meaburn EL, Ronald A, Price TS, Jeffries AR, et al. (2013) Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Mol Psychiatry.

[3] Ladd-Acosta C, Hansen KD, Briem E, Fallin MD, Kaufmann WE, et al. (2013) Common DNA methylation alterations in multiple brain regions in autism. Mol Psychiatry.

Epigenetics and Drug Discovery: The Missing Link?

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by Shea Robison (@EpigeneticsGuy)

(This post was also featured by the genomics-focused multimedia outlet Front Line Genomics on February 4, 2015, available here. Front Line Genomics have also invited me to write a guest piece for their magazine about epigenetics and cancer, so stay tuned for that as well.)

In a recent post titled “Phenotype matters!”, Robert Plenge, Vice President and Head of the newly created Department of Genetics & Pharmacogenomics at Merck, begins with the premise that “for drug discovery…human genetics is a useful tool to uncover novel drug targets that are likely to have unambiguous promotable advantage.” From this premise Dr. Plenge promotes  the idea that the most effective use of genetic studies of this kind is to “pick the right phenotype, one that is an appropriate surrogate for drug efficacy.”

As examples of the importance of phenotype in effective drug discovery, Plenge discusses type I diabetes and rheumatoid arthritis. For type I diabetes, Plenge observes that geneticists have identified a number of alleles associated with increased risk for this disease, “nearly all of which act on the immune system (see here).” Given the identification of these genetic components, Plenge writes, we would expect drug therapies that alter the immune system to prevent development of the disease. However, the primary treatments for type I diabetes  focus on the administration of insulin “thus, the genetic pathways that lead to the development of type 1 diabetes (immune dysregulation) are different from the biological pathways that are relevant for treating type 1 diabetes once diagnosed (glucose homeostasis).” In contrast, “in patients with rheumatoid arthritis the immunological pathways that lead to the disease also seem to be related to the immunological pathways that contribute to symptoms in patients with established disease,” which pathways are the targets for effective drug therapies for rheumatoid arthritis.

Plenge uses these examples to pose the question: “Are the genetic pathways that lead to disease the same as the pathways that should be modulated to treat the disease?” And asks his readers to consider phenotypes such as asthma, heart failure and type 2 diabetes in the context of this question, arguing that some of these phenotypes are more relevant to drug discovery than others. Plenge then observes that one good way to answer his own question is “if prior genetic data link a clinical phenotype and an approved therapy, then this provides strong evidence that the clinical phenotype is relevant for drug discovery.” He then refers to the results of genome-wide association studies (GWASs) of psoriasis and osteoporosis as providing evidence of these as more relevant phenotypes, and of developmental diseases (e.g., autism and congenital heart defects) and degenerative diseases (e.g., Alzheimer’s) as examples of less relevant phenotypes. In regards to the latter, Plenge writes that while “genetics may uncover targets that, if pharmacologically modulated prior to disease onset, may prevent development of disease…it seems less likely that genetics will uncover targets that can be modulated once the disease is established.” Plenge does allow that as biological knowledge evolves such phenotypes may become more relevant in the future “as additional knowledge about biological pathways is learned,” but that for now efforts at drug discovery are best confined to these more relevant phenotypes as identified through genomics.

I concede to Dr. Plenge’s expertise in this area in terms of the current practices based on contemporary genetics. However, his emphasis on the importance of phenotype for drug discovery raises what I think is a critically important aspect which is missed by this conventional approach based solely on genetics and genomics: The role of epigenetics in the expression of these phenotypes.

I have already posted about what epigenetics adds—or could add—to such gene-focused searches for the genetic correlates of diseases and disorders. In this previous post I discuss how while GWASs can reveal the sequences of genes associated with certain phenotypes such as those mentioned by Dr. Plenge, GWASs [to my knowledge] do not reveal anything about the three-dimensional structure of genomes which can also have a significant effect on gene regulation and expression. This structure is both determined and manipulable through the epigenome (in particular, through the methylation/demethylation or acetylation/deacetylation of chromatin and histones) in response to a host of environmental conditions. Thus, my recommendation in this previous post is that including epigenetics with genomics will allow for the analysis of both the sequence and the structure, and should only enhance the diagnostic and predictive power of such processes.

The observations of Dr. Plenge introduce another wrinkle into this discussion about what epigenetics can add to genomics. It is interesting to me that the phenotypes Plenge identifies as “less relevant” are precisely those which are the focus of so much research in epigenetics (see here for an extensive list of Q&As with experts working in epigenetics in different areas). In other words, while the biological pathways of some phenotypes may be difficult to target with effective drug treatments using conventional gene-focused methods, these same pathways appear to be identifiable via epigenetics—in ways which are capable of addressing not just the symptoms of the disease phenotype but the actual biological sources of the phenotype, just as Dr. Plenge recommends.

For example, consider the phenotypes of impaired brain development, abnormal sexual differentiation and impaired immune function. Because these are developmental disorders, according to Dr. Plenge, once these diseases are established “it seems less likely that genetics will uncover targets that can be modulated,” which makes them “less relevant” for drug discovery via genomics.

However, research in both animals and humans has linked these same phenotypes, among many other effects, with ingestion of the synthetic chemical bisphenol A (BPA) through epigenetic effects.[1] Because these phenotypes have been found to manifest through modifications of the epigenome,[2] the biological pathways of the diseases themselves and not just their symptoms have been identified, just as recommended by Dr. Plenge. What is more, very specific treatments for such disease phenotypes have been found via epigenetics —as in this study which found that maternal dietary supplementation with methyl donors “negated the DNA hypomethylating effect of BPA.”[3] Although this maternal supplementation does not ‘modulate the target’ once the disease is established, to paraphrase Dr. Plenge, prior [epi-]genetic data does link a clinical phenotype and an approved therapy, which “provides strong evidence that the clinical phenotype is relevant for drug discovery.”

Epigenetic pathways have also been found for other “less relevant” phenotypes explicitly mentioned by Dr. Plenge, such as autism.[4] Significant attention is already being focused on the epigenetic aspects of autism – see germlineexposures.org and autismepigenetics.org – as potential avenues for the treatment and possibly the cure for autism.  This identification of the pathways of these phenotypes and not just of the symptoms of the phenotypes should therefore, according to Dr. Plenge. move these disorders from the “less relevant” to the “more relevant” category in terms of developing targeted pharmaceutical therapies.

What is noteworthy, though, is that epigenetics—or even any consideration of epigenetic mechanisms—are not mentioned by Dr. Plenge. This oversight is understandable in one sense, in that no one can or should be expected to be a specialist about everything; in another sense, though, this oversight carries some rather significant implications for all those who currently suffer from disease phenotypes which are ‘less relevant’ via genomics, as well as for all those who will suffer from diseases such as “autism, congenital heart defects…late-stage Alzheimer’s disease, end-stage kidney disease,” to name only those phenotypes mentioned by Dr. Plenge. That such suffering could be alleviated by the seemingly simple combination of genomics with epigenetics seems incentive enough to pursue the unification of these two fields (as recommended here by Dr. Randy Jirtle).

Given the magnitude of the possible benefits of unification, that there is still such an unawareness or even outright hostility towards epigenetics by many geneticists is curious. Science-based doubts about the results of epigenetic research are understandable enough, and resolvable through science-based back-and-forth; the non-science based opprobrium directed towards epigenetics is not so understandable. Detailing the historical, political and philosophical reasons for this antipathy and even antagonism towards epigenetics is a primary focus of this blog, as discussed in posts too numerous to mention.

My intentions for writing this post and this blog are not as some diatribe against genetics or genomics; rather I see the benefits of both genomics and epigenetics, and would like to see the unification of both which would provide a more complete picture of ourselves and of our relationships to each other, and of our place in the world around us. Hopefully posts like this contribute to this project.

Is the unification of epigenetics and genomics possible? Is it probable? What would have to occur for this unification to take place? What are some of the ways this unification could take place? Or is genomics fine without epigenetics (and vice versa)?

I am curious to hear what you think. Leave your comments below and I will respond.

Also, if you find these thoughts I’ve shared interesting and worthwhile, Like this post, Reblog it, or Tweet about it using the buttons below.

[1] Muhlhauser, A., Susiarjo, M., Rubio, C., Griswold, J., Gorence, G., Hassold, T., & Hunt, P. A. (2009). Bisphenol A effects on the growing mouse oocyte are influenced by diet. Biology of reproduction, 80(5), 1066-1071; Staples, C. A., Dome, P. B., Klecka, G. M., Oblock, S. T., & Harris, L. R. (1998). A review of the environmental fate, effects, and exposures of bisphenol A. Chemosphere, 36(10), 2149-2173; Vom Saal, F. S., & Hughes, C. (2005). An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environmental health perspectives, 926-933; Watts, M. M., Pascoe, D., & Carroll, K. (2001). Chronic exposure to 17α-ethinylestradiol and bisphenol A-effects on development and reproduction in the freshwater invertebrate Chironomus riparius (Diptera: Chironomidae).Aquatic Toxicology, 55(1), 113-124; Welshons, W. V., Nagel, S. C., & vom Saal, F. S. (2006). Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology, 147(6), s56-s69.

[2] Bromer, J. G., Zhou, Y., Taylor, M. B., Doherty, L., & Taylor, H. S. (2010). Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. The FASEB Journal, 24(7), 2273-2280; Kundakovic, M., & Champagne, F. A. (2011). Epigenetic perspective on the developmental effects of bisphenol A. Brain, behavior, and immunity, 25(6), 1084-1093; Singh, S., & Li, S. S. L. (2012). Epigenetic effects of environmental chemicals bisphenol a and phthalates. International journal of molecular sciences, 13(8), 10143-10153.

[3] Dolinoy, D. C., Huang, D., & Jirtle, R. L. (2007). Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proceedings of the National Academy of Sciences, 104(32), 13056-13061.

[4] Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., … & Pericak-Vance, M. A. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC medicine, 7(1), 62; Jenkins, T. G., Aston, K. I., Pflueger, C., Cairns, B. R., & Carrell, D. T. (2014). Age-Associated Sperm DNA Methylation Alterations: Possible Implications in Offspring Disease Susceptibility. PLoS genetics, 10(7), e1004458; Morrow Jr, K. J. (2014). Cancer, Autism and Their Epigenetic Roots. McFarland; Nguyen, A., Rauch, T. A., Pfeifer, G. P., & Hu, V. W. (2010). Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. The FASEB Journal, 24(8), 3036-3051; Zhubi, A. (2014). Alterations of Epigenetic Mechanisms in post-mortem Autism Spectrum Disorder (ASD) subjects (Doctoral dissertation, University of Illinois at Chicago).