'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Sat, 28 May 2016 23:48:06 PDT Sat, 28 May 2016 23:48:06 PDT jirtle@radonc.duke.edu james001@jirtle.com Endocrine therapy resistance in estrogen receptor (ER)-positive breast cancer. De Marchi T, Foekens JA, Umar A, Martens JW
Drug Discov Today (May 2016)

Estrogen receptor (ER)-positive breast cancer represents the majority (∼70%) of all breast malignancies. In this subgroup of breast cancers, endocrine therapies are effective both in the adjuvant and recurrent settings, although resistance remains a major issue. Several high-throughput approaches have been used to elucidate mechanisms of resistance and to derive potential predictive markers or alternative therapies. In this review, we cover the state-of-the-art of endocrine-resistance biomarker discovery with regard to the latest technological developments, and discuss current opportunities and restrictions for their implementation into a clinical setting.]]>
Sat, 28 May 2016 00:00:00 PDT
Plasma Amyloid Beta 1-42 and DNA Methylation Pattern Predict Accelerated Aging in Young Subjects with Down Syndrome. Obeid R, Hübner U, Bodis M, Geisel J
Neuromolecular Med (May 2016)

Gene methylation is an age-related dynamic process that influences diseases. Premature aging and disturbed methylation are components of Down syndrome (DS). We studied blood biomarkers and DNA methylation (DNAm) of three CpG sites (ASPA, ITGA2B, and PDE4C) in 60 elderly subjects (mean age = 68 years), 31 subjects with DS (12.1 years) and 44 controls (12.8 years). Plasma concentrations of amyloid beta (Aβ) 1-42 and biomarkers of methylation were measured in the young groups. Subjects with DS had significantly higher concentrations of plasma S-adenosylhomocysteine (SAH) and Aβ and reduced S-adenosylmethionine/SAH ratio compared with the controls. Methylations (%) of ASPA and ITGA2B were lower in DS [mean difference; 95 % confidence intervals = -2.2 (-4.5, 0.1) for ASPA and -5.0 (-8.9, -1.1) for ITGA2B]. Methylation of PDE4C did not differ between the groups. The sum of z-scores for methylations of ASPA and ITGA2B, both of which declined with age, was significantly lower in DS [-1.01 (-1.93, -0.20), p = 0.017]. Subjects with DS were found to be 3.1 (1.5-4.6) years older than their predicted age based on a regression model of the controls. Elevated SAH levels predicted lower DNAm of ASPA and ITGA2B in stepwise regression analysis. Therefore, methylation of three CpGs combined with plasma Aβ has shown a 3-year accelerated aging in subjects with DS at the age of 12 years. Disorders in the methylation cycle explained pathoepigenetic modifications in subjects with DS. The influence of modifications in the methylation cycle on epigenetic markers of aging warrants further investigations.]]>
Sat, 28 May 2016 00:00:00 PDT
H19ICR mediated transcriptional silencing does not require target promoter methylation. Gebert C, Rong Q, Jeong S, Iben J, Pfeifer K
Biochem Biophys Res Commun (May 2016)

Transcription of the reciprocally imprinted genes Insulin-like growth factor 2 (Igf2) and H19 is orchestrated by the 2.4-kb H19 Imprinting Control Region (H19ICR) located upstream of H19. Three known functions are associated with the H19ICR: (1) it is a germline differentially methylated region, (2) it is a transcriptional insulator, and (3) it is a transcriptional silencer. The molecular mechanisms of the DMR and insulator functions have been well characterized but the basis for the ICR's silencer function is less well understood. In order to study the role the H19ICR intrinsically plays in gene silencing, we transferred the 2.4-kb H19ICR to a heterologous non-imprinted location on chromosome 5, upstream of the alpha fetoprotein (Afp) promoter. Independent of its orientation, the 2.4-kb H19ICR silences transcription from the paternal Afp promoter. Thus silencing is a function intrinsic to this DNA element. Further, ICR mediated silencing is a developmental process that, unexpectedly, does not occur through DNA methylation at the target promoter.]]>
Wed, 25 May 2016 00:00:00 PDT
Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study. Walton E, Pingault JB, Cecil CA, Gaunt TR, Relton CL, Mill J, Barker ED
Mol Psychiatry (May 2016)

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent developmental disorder, associated with a range of long-term impairments. Variation in DNA methylation, an epigenetic mechanism, is implicated in both neurobiological functioning and psychiatric health. However, the potential role of DNA methylation in ADHD symptoms is currently unclear. In this study, we examined data from the Avon Longitudinal Study of Parents and Children (ALSPAC)-specifically the subsample forming the Accessible Resource for Integrated Epigenomics Studies (ARIES)-that includes (1) peripheral measures of DNA methylation (Illumina 450k) at birth (n=817, 49% male) and age 7 (n=892, 50% male) and (2) trajectories of ADHD symptoms (7-15 years). We first employed a genome-wide analysis to test whether DNA methylation at birth associates with later ADHD trajectories; and then followed up at age 7 to investigate the stability of associations across early childhood. We found that DNA methylation at birth differentiated ADHD trajectories across multiple genomic locations, including probes annotated to SKI (involved in neural tube development), ZNF544 (previously implicated in ADHD), ST3GAL3 (linked to intellectual disability) and PEX2 (related to perixosomal processes). None of these probes maintained an association with ADHD trajectories at age 7. Findings lend novel insights into the epigenetic landscape of ADHD symptoms, highlighting the potential importance of DNA methylation variation in genes related to neurodevelopmental and peroxisomal processes that play a key role in the maturation and stability of cortical circuits.Molecular Psychiatry advance online publication, 24 May 2016; doi:10.1038/mp.2016.85.]]>
Tue, 24 May 2016 00:00:00 PDT
The Role of STAT Signaling Pathways in the Pathogenesis of Systemic Lupus Erythematosus. GoropevÅ¡ek A, Holcar M, Avčin T
Clin Rev Allergy Immunol (May 2016)

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a broad spectrum of clinical presentations and association with multiple immunological abnormalities. Recent research of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway-revealed aberrant STAT signaling in inflammatory conditions and autoimmune diseases including SLE. STAT proteins are major components in interferon (IFN)-dependent gene expression and are responsible for signal transduction of over 50 cytokines, hormones, and growth factors regulating key cellular processes such as survival, proliferation, and differentiation. This review summarizes the present evidence from experimental animal models and patients with SLE for the involvement of STAT pathways in the pathogenesis of SLE underlining the role of different members of the STAT family. Genome-wide association studies provided evidence that variations in STAT4 gene are linked to the development of SLE in humans. First integration with genome-wide epigenomics data suggests that control of CD4+ T cell differentiation in which STATs play a major role may be an important component of the genetic contribution to disease susceptibility. Increased transcript and total protein STAT1 levels were described both in SLE T and B cells suggestive of the priming mechanisms that augment STAT1 signaling responses to IFN. STAT3 has a crucial role in Th17 differentiation, T follicular helper, and B cells, and STAT3 inhibition could represent a possible future therapeutic target in SLE. STAT5B appears to act as a critical modulator of human Treg development and function. While the imbalance between phosphorylated STAT5 and STAT3 in human SLE T cells was implicated in dysregulated IL-10 expression, Treg-specific deletion of STAT3 in mouse model even enhanced Th17-mediated inflammation. Finally, we present also a comprehensive analysis of studies investigating STAT signaling responses in conventional and regulatory subsets of SLE T and B cells and possible implications of STAT inhibition for clinical therapy.]]>
Tue, 24 May 2016 00:00:00 PDT
Tumor purity and differential methylation in cancer epigenomics. Wang F, Zhang N, Wang J, Wu H, Zheng X
Brief Funct Genomics (May 2016)

DNA methylation is an epigenetic modification of DNA molecule that plays a vital role in gene expression regulation. It is not only involved in many basic biological processes, but also considered an important factor for tumorigenesis and other human diseases. Study of DNA methylation has been an active field in cancer epigenomics research. With the advances of high-throughput technologies and the accumulation of enormous amount of data, method development for analyzing these data has gained tremendous interests in the fields of computational biology and bioinformatics. In this review, we systematically summarize the recent developments of computational methods and software tools in high-throughput methylation data analysis with focus on two aspects: differential methylation analysis and tumor purity estimation in cancer studies.]]>
Fri, 20 May 2016 00:00:00 PDT
Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time. Filbin MG, Suvà ML
Annu Rev Pathol (May 2016)

Gliomas are the most common primary human brain tumors and occur in both adults and children. Over the past few years, systematic large-scale genomic and epigenomic profiling has provided unprecedented insight into their pathogenesis, uncovering alterations in an unanticipated number of genes and regulatory elements. In this review, we discuss recent discoveries about the genomics and epigenomics of adult and pediatric gliomas and highlight how some of the founding genetic mutations reshape the cancer epigenome. These studies provide an in-depth view of the molecular routes leading to glioma development, offer insight into the cancer stem cell model, help refine classifications, and should lay the foundation for improved clinical care.]]>
Thu, 19 May 2016 00:00:00 PDT
Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment response in rheumatoid arthritis. Márquez A, Martín J, Carmona FD
Expert Rev Mol Diagn (Jun 2016)

Important advances have occurred during the last decade in the understanding of the pathogenesis of rheumatoid arthritis (RA). However, we are still far from having a clear picture of the molecular network that predisposes an individual to develop the disease, to worsen the symptoms after that, or to successfully respond to a specific treatment. In this sense, different -omics fields (including transcriptomics, proteomics, metabolomics, genomics and epigenomics) have recently produced promising insights that could definitively help us to sharpen such picture if integrated trough a systems biology approach. In this review we will summarise and discuss the recent progress achieved in those fields and its possible impact on the discovery of suitable biomarkers for RA diagnosis, prognosis and treatment response.]]>
Thu, 19 May 2016 00:00:00 PDT
Chromatin and epigenetics in all their states: Meeting report of the first conference on Epigenetic and Chromatin Regulation of Plant Traits - January 14 - 15, 2016 - Strasbourg, France. Bey T, Jamge S, Klemme S, Komar DN, Le Gall S, Mikulski P, Schmidt M, Zicola J, Berr A
Epigenetics (May 2016)

In January 2016, the first Epigenetic and Chromatin Regulation of Plant Traits conference was held in Strasbourg, France. An all-star lineup of speakers, a packed audience of 130 participants from over 20 countries, and a friendly scientific atmosphere contributed to make this conference a meeting to remember. In this article we summarize some of the new insights into chromatin, epigenetics, and epigenomics research and highlight nascent ideas and emerging concepts in this exciting area of research.]]>
Tue, 17 May 2016 00:00:00 PDT
Genetic sources of population epigenomic variation. Taudt A, Colomé-Tatché M, Johannes F
Nat Rev Genet (Jun 2016)

The field of epigenomics has rapidly progressed from the study of individual reference epigenomes to surveying epigenomic variation in populations. Recent studies in a number of species, from yeast to humans, have begun to dissect the cis- and trans-regulatory genetic mechanisms that shape patterns of population epigenomic variation at the level of single epigenetic marks, as well as at the level of integrated chromatin state maps. We show that this information is paving the way towards a more complete understanding of the heritable basis underlying population epigenomic variation. We also highlight important conceptual challenges when interpreting results from these genetic studies, particularly in plants, in which epigenomic variation can be determined both by genetic and epigenetic inheritance.]]>
Tue, 17 May 2016 00:00:00 PDT
Beyond DNA puffs: What can we learn from studying sciarids? Simon CR, Siviero F, Monesi N
Genesis (May 2016)

Members of the Sciaridae family attracted the interest of researchers because of the demonstration that the DNA puff regions, which are formed in the salivary gland polytene chromosomes at the end of the fourth larval instar, constitute sites of developmentally regulated gene amplification. Besides contributing to a deeper understanding of the process of gene amplification, the study of sciarids has also provided important insights on other biological processes such as sex determination, programmed cell death, insect immunity, telomere maintenance and nucleolar organizing regions (NOR) formation. Open questions in sciarids include among others, early development, the role of non coding RNAs in gene amplification and the relationship between gene amplification and transcription in DNA puff forming regions. These and other questions can now be pursued with next generation sequencing techniques and experiments using RNAi experiments, since this latter technique has been shown to be feasible in sciarids. These new perspectives in the field of sciarid biology open the opportunity to consolidate sciarid species as important emerging models. This article is protected by copyright. All rights reserved.]]>
Sat, 14 May 2016 00:00:00 PDT
Long non-coding RNAs in normal and malignant hematopoiesis. Nobili L, Lionetti M, Neri A
Oncotarget (May 2016)

Long non coding RNAs (lncRNAs) are defined as ncRNAs of more than 200 nt in length. They are involved in a large spectrum of biological processes, such as maintenance of genome integrity, genomic imprinting, cell differentiation, and development by means of mechanisms that remain to be fully elucidated. Besides their role in normal cellular physiology, accumulating evidence has linked lncRNA expression and functions to cancer development and progression. In this review, we summarize and discuss what is known about their expression and roles in hematopoiesis with a particular focus on their cell-type specificity, functional interactions, and involvement in the pathobiology of hematological malignancies.]]>
Fri, 13 May 2016 00:00:00 PDT
Association of interleukin-6 methylation in leukocyte DNA with serum level and the risk of ischemic heart disease. Yang Q, Zhao Y, Zhang Z, Chen J
Scand J Clin Lab Invest (Jul 2016)

Background Interleukin-6 (IL-6), a multifunctional cytokine, plays an important role in the development of ischemic heart disease (IHD), and DNA hypomethylation of 2 CpGs, located downstream in the proximity of the IL-6 gene promoter, has been associated with risk factor for IHD. This study was to examine the association of blood leukocyte DNA methylation of the 2 CpGs in IL-6 with the risk of IHD and the serum IL-6 level. Methods IL-6 methylation levels of 582 cases and 673 controls were measured using the bisulfite pyrosequencing technology. Serum level of IL-6 was measured using enzyme-linked immunosorbent assay. Results The IL-6 methylation was significantly lower in IHD cases than in the controls, irrespective of CpG site. After multivariate adjustment, lower (< median) average IL-6 methylation was associated with an increased risk of IHD (OR 1.57, 95% CI 1.22-2.02, p < 0.001). Average IL-6 methylation level was inversely associated with serum IL-6 level (β = -1.02 pg/mL per increase in IL-6 methylation, p = 0.002) among IHD cases. This significant relationship was not observed among controls. Conclusions DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of IHD. IL-6 demethylation may upregulate its expression, whereby exerting its risk effect on the development of IHD.]]>
Fri, 13 May 2016 00:00:00 PDT
Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalised Nutrition: Part 1 - Fields of Precision Nutrition. Ferguson LR, De Caterina R, Görman U, Allayee H, Kohlmeier M, Prasad C, Choi MS, Curi R, de Luis DA, Gil Ã, Kang JX, Martin RL, Milagro FI, Nicoletti CF, Nonino CB, Ordovas JM, Parslow VR, Portillo MP, Santos JL, Serhan CN, Simopoulos AP, Velázquez-Arellano A, Zulet MA, Martinez JA
J Nutrigenet Nutrigenomics (May 2016)

Diversity in the genetic profile between individuals and specific ethnic groups affects nutrient requirements, metabolism and response to nutritional and dietary interventions. Indeed, individuals respond differently to lifestyle interventions (diet, physical activity, smoking, etc.). The sequencing of the human genome and subsequent increased knowledge regarding human genetic variation is contributing to the emergence of personalized nutrition. These advances in genetic science are raising numerous questions regarding the mode that precision nutrition can contribute solutions to emerging problems in public health, by reducing the risk and prevalence of nutrition-related diseases. Current views on personalized nutrition encompass omics technologies (nutrigenomics, transcriptomics, epigenomics, foodomics, metabolomics, metagenomics, etc.), functional food development and challenges related to legal and ethical aspects, application in clinical practice, and population scope, in terms of guidelines and epidemiological factors. In this context, precision nutrition can be considered as occurring at three levels: (1) conventional nutrition based on general guidelines for population groups by age, gender and social determinants; (2) individualized nutrition that adds phenotypic information about the person's current nutritional status (e.g. anthropometry, biochemical and metabolic analysis, physical activity, among others), and (3) genotype-directed nutrition based on rare or common gene variation. Research and appropriate translation into medical practice and dietary recommendations must be based on a solid foundation of knowledge derived from studies on nutrigenetics and nutrigenomics. A scientific society, such as the International Society of Nutrigenetics/Nutrigenomics (ISNN), internationally devoted to the study of nutrigenetics/nutrigenomics, can indeed serve the commendable roles of (1) promoting science and favoring scientific communication and (2) permanently working as a 'clearing house' to prevent disqualifying logical jumps, correct or stop unwarranted claims, and prevent the creation of unwarranted expectations in patients and in the general public. In this statement, we are focusing on the scientific aspects of disciplines covering nutrigenetics and nutrigenomics issues. Genetic screening and the ethical, legal, social and economic aspects will be dealt with in subsequent statements of the Society.]]>
Thu, 12 May 2016 00:00:00 PDT
Brain Radiation Information Data Exchange (BRIDE): integration of experimental data from low-dose ionising radiation research for pathway discovery. Karapiperis C, Kempf SJ, Quintens R, Azimzadeh O, Vidal VL, Pazzaglia S, Bazyka D, Mastroberardino PG, Scouras ZG, Tapio S, Benotmane MA, Ouzounis CA
BMC Bioinformatics (2016)

The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being explored using omics technologies.]]>
Thu, 12 May 2016 00:00:00 PDT
Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures. Wang X, Tucker NR, Rizki G, Mills R, Krijger PH, de Wit E, Subramanian V, Bartell E, Nguyen XX, Ye J, Leyton-Mange J, Dolmatova EV, van der Harst P, de Laat W, Ellinor PT, Newton-Cheh C, Milan DJ, Kellis M, Boyer LA
Elife (2016)

Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits.]]>
Tue, 10 May 2016 00:00:00 PDT
Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation. Do C, Lang CF, Lin J, Darbary H, Krupska I, Gaba A, Petukhova L, Vonsattel JP, Gallagher MP, Goland RS, Clynes RA, Dwork A, Kral JG, Monk C, Christiano AM, Tycko B
Am J Hum Genet (May 2016)

Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A(∗)-ILF2, associated with immune phenotypes, MYT1L, PTPRN2, CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites were over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to macaques, indicated that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; and variation in CTCF and TF binding sites is an underlying mechanism, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supra- and sub-threshold GWAS peaks in immunological and neurological disorders.]]>
Sat, 07 May 2016 00:00:00 PDT
Childhood obesity: a systems medicine approach. Stone WL, Schetzina K, Stuart C
Front Biosci (Landmark Ed) (2016)

Childhood obesity and its sequelae are a major public health problem in both the USA and globally. This review will focus on a systems medicine approach to obesity. Systems medicine is an integrative approach utilizing the vast amount of data garnered from "omics" technology and integrating these data with conventional pathophysiology as well as diverse environmental factors such as diet, exercise, community dynamics and the intestinal microbiome. Omics technology includes genomics, epigenomics, metagenomics, metabolomics and proteomics. In addition to unraveling etiology, the goals of a systems medicine approach are to provide actionable and evidenced-based clinical approaches. In the case of childhood obesity, an additional goal is characterizing measureable risk factors/biomarkers for obesity at the earliest possible age and devising age-appropriate optimal intervention strategies. It is also important to establish the age at which interventions could be critical. As discussed below, it is possible that some of the pathophysiological and epigenetic changes resulting from childhood obesity could become more irreversible the longer the obesity remains untreated.]]>
Fri, 22 Apr 2016 00:00:00 PDT
Biomarkers in neonatology: the new "omics" of bronchopulmonary dysplasia. Piersigilli F, Bhandari V
J Matern Fetal Neonatal Med (Jun 2016)

Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from gene-environmental interactions. An improved understanding of the pathogenesis of this most common chronic lung disease in infants has been made by utilizing animal models and correlating with human data. Currently, while some (vitamin A, caffeine) pharmacotherapeutic options are being utilized to ameliorate this condition, there is still no specific or effective treatment for BPD. It would be helpful for prognostication and targeted potential novel therapeutic strategies to identify those babies accurately who are at risk for developing this disease. A reliable biomarker would have the capacity to be detected in the initial phase of the disease, to allow early interventions to avoid or minimize the detrimental effects of the disease. This review will focus on human studies performed with the "omic" techniques, specifically genomics, epigenomics, microbiomics, transciptomics, proteomics and metabolomics, and summarize the information available in the literature, as it pertains to biomarker identification for BPD. Using "omics" technologies, investigators have reported markers that have the potential to be used as biomarkers of BPD: SPOCK2, VEGF -624C > G, VEGF -460T > C, mast cells specific markers, miR-219 pathway, miR-152, -30a-3p, -133b, -206, -7, lactate, taurine, trimethylamine-N-oxide, gluconate, myoinositol and alterations in surfactant lipid profile.]]>
Fri, 25 Mar 2016 00:00:00 PDT
DNA methylation analysis in constitutional disorders: Clinical implications of the epigenome. Schenkel LC, Rodenhiser DI, Ainsworth PJ, Paré G, Sadikovic B
Crit Rev Clin Lab Sci (Jun 2016)

Genomic, chromosomal, and gene-specific changes in the DNA sequence underpin both phenotypic variations in populations as well as disease associations, and the application of genomic technologies for the identification of constitutional (inherited) or somatic (acquired) alterations in DNA sequence forms a cornerstone of clinical and molecular genetics. In addition to the disruption of primary DNA sequence, the modulation of DNA function by epigenetic phenomena, in particular by DNA methylation, has long been known to play a role in the regulation of gene expression and consequent pathogenesis. However, these epigenetic factors have been identified only in a handful of pediatric conditions, including imprinting disorders. Technological advances in the past decade that have revolutionized clinical genomics are now rapidly being applied to the emerging discipline of clinical epigenomics. Here, we present an overview of epigenetic mechanisms with a focus on DNA modifications, including the molecular mechanisms of DNA methylation and subtypes of DNA modifications, and we describe the classic and emerging genomic technologies that are being applied to this study. This review focuses primarily on constitutional epigenomic conditions associated with a spectrum of developmental and intellectual disabilities. Epigenomic disorders are discussed in the context of global genomic disorders, imprinting disorders, and single gene disorders. We include a section focused on integration of genetic and epigenetic mechanisms together with their effect on clinical phenotypes. Finally, we summarize emerging epigenomic technologies and their impact on diagnostic aspects of constitutional genetic and epigenetic disorders.]]>
Tue, 16 Feb 2016 00:00:00 PST