Associative DNA Methylation Changes in Children with Prenatal Alcohol Exposure

Laufer, Benjamin I.; Kapalanga, Joachim; Castellani, Christina A; Diehl, Eric J.; Yan, Liying; Singh, Shiva M.

doi:10.2217/epi.15.60

Cited by 91 publications

(87 citation statements)

References 60 publications

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“…Though it remains to be demonstrated that reduced γ-Pcdh protein levels are causal for any of the dendritic or synaptic defects seen in DS, the phenotypes observed in Pcdhg null cortex (as discussed above, decreased dendrite arborization and altered dendritic spine number and morphology) are certainly consistent with such a possibility [54,82]. Studies exploring methylation patterns in FASD similarly discovered increased methylation of the clustered Pcdhs both in the brains of FASD mouse models and in buccal cells of human FASD patients [168,169]. …”

Section: Roles In Behavior and Neurological Or Neurodevelopmental Dismentioning

confidence: 96%

Regulation of neural circuit formation by protocadherins

Peek

Mah

Weiner

2017

Cell. Mol. Life Sci.

114

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The Protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990's. Data implicating the Pcdhs, including ∼60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ∼10 non-clustered Pcdhs, in the regulation of neural development has continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination. We further discuss studies implicating mutation or epigenetic dysregulation of Pcdh genes in a variety of human neurodevelopmental and neurological disorders. With recent structural modeling of Pcdh proteins, the prospects for uncovering molecular mechanisms of Pcdh extracellular and intracellular interactions, and their role in normal and disrupted neural circuit formation, are bright.

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Section: Roles In Behavior and Neurological Or Neurodevelopmental Dismentioning

confidence: 96%

Regulation of neural circuit formation by protocadherins

Peek

Mah

Weiner

2017

Cell. Mol. Life Sci.

114

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“…Decreased DNA methylation and increased H4 acetylation in the ovary Alcohol Human/ cohort study Association between maternal alcohol and DNA methylation in whole blood/buccal tissues of children (1-16 years) [265,267] Hypomethylation of the KvDMR1 and PEG3 DMR Differential methylation of 269 CpGs on multiple genes related to protocadherins, glutamatergic synapses, and hippocampal signaling Human/ cohort study Association between periconceptional alcohol use in parents and cord blood methylation levels [266] Hypomethylation of the DAT gene promoter due to maternal (before and during pregnancy) and paternal (before conception) alcohol use…”

Section: Hypomethylation Of the Pancreatic Il13ra2 Genementioning

confidence: 99%

“…Increasing body of evidence indicates that epigenetic alterations may underlie the changes characteristic of fetal alcohol syndrome. [264] Prenatal exposure to alcohol is demonstrated to induce extensive DNA methylation changes in human [265][266][267] and rodent offsprings ( Table 2). [110,112,114,120,128,[268][269][270][271][272] These effects are possibly transmitted via methylation of the paternal germ line, [273] although alcohol-induced placental epigenetic changes suggest the involvement of the female germ line.…”

Section: Smoking Alcohol Pollutants and Other Environmental Chemicalsmentioning

confidence: 99%

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease

Imam

Ismail

2017

Global Challenges

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There are already extensive reviews on the global burden of NCCDs in the public domain. [1][2][3][4][5][6] The consensus that can be surmised from the available data on NCCDs is that their overall prevalence appears to be rising globally and the projections indicate an upward trend. Epidemiological transition data suggests that the morbidity and mortality rate from these diseases is far more than that of communicable diseases in the developed world [7] and a similar trend is now occurring in the low to medium income countries (LMICs). [8] Among the NCCDs, cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality, followed closely by metabolic diseases like Noncommunicable chronic diseases (NCCDs) are the leading causes of morbidity and mortality globally. The mismatch between present day diets and ancestral genome is suggested to contribute to the NCCDs burden, which is promoted by traditional risk factors like unhealthy diets, physical inactivity, alcohol and tobacco. However, epigenetic evidence now suggests that cumulatively inherited epigenetic modifications may have made humans more prone to the effects of present day lifestyle factors. Perinatal starvation was widespread in the 19th century. This together with more recent events like increasing consumption of western and low fiber diets, smoking, harmful use of alcohol, physical inactivity, and environmental pollutants may have programed the human epigenome for higher NCCDs risk. In this review, on the basis of available epigenetic data it is hypothesized that transgenerational effects of lifestyle factors may be contributing to the current global burden of NCCDs. Thus, there is a need to reconsider prevention strategies so that the subsequent generations will not have to pay for our sins and those of our ancestors. Cardiovascular DiseasesDr. M. U. Imam

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“…Since this initial work, other studies have identified heritable alterations in chromatin structure arising from early gestational exposures, suggesting epigenetic mechanisms are relevant to the development of FASDs (Chen et al, 2013, Veazey et al, 2015, Zhang et al, 2015, Marjonen et al, 2015). As an example, studies examining blood samples derived from FAS children have demonstrated altered DNA methylation within the regulatory regions of select imprinted genes, suggesting that alcohol-induced alterations in chromatin structure may persist through development and into early adulthood (Laufer et al, 2015, Masemola et al, 2015). Interestingly, recent work suggests some of these epigenetic lesions may transmit through the male germline into the next generation (Govorko et al, 2012).…”

Section: Epigenetic Mechanisms Underlying Dohadmentioning

confidence: 99%

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

Lunde

Washburn

Golding

et al. 2016

Alcohol Clin Exp Res

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Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD.

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Associative DNA Methylation Changes in Children with Prenatal Alcohol Exposure

Cited by 91 publications

References 60 publications

Regulation of neural circuit formation by protocadherins

Regulation of neural circuit formation by protocadherins

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

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