'; ?> 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 Thu, 23 Nov 2017 10:42:41 PST Thu, 23 Nov 2017 10:42:41 PST jirtle@radonc.duke.edu james001@jirtle.com Denise Barlow (1950-2017)-pioneer of genomic imprinting. Wutz A
EMBO Rep (Nov 2017)

Wed, 22 Nov 2017 00:00:00 PST
Novel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: case report and review of the literature. Aguilera C, Viñas-Jornet M, Baena N, Gabau E, Fernández C, Capdevila N, Cirkovic S, Sarajlija A, Miskovic M, Radivojevic D, Ruiz A, Guitart M
BMC Med Genet (Nov 2017)

Patients with Angelman syndrome (AS) are affected by severe intellectual disability with absence of speech, distinctive dysmorphic craniofacial features, ataxia and a characteristic behavioral phenotype. AS is caused by the lack of expression in neurons of the UBE3A gene, which is located in the 15q11.2-q13 imprinted region. Functional loss of UBE3A is due to 15q11.2-q13 deletion, mutations in the UBE3A gene, paternal uniparental disomy and genomic imprinting defects.]]>
Wed, 22 Nov 2017 00:00:00 PST
Breast cancer protection by genomic imprinting in close kin families. Denic S, Agarwal MM
BMC Med Genet (Nov 2017)

Human inbreeding generally reduces breast cancer risk (BCR). When the parents are biologically related, their infants have a lower birth weight due to smaller body organs. The undersized breasts, because of fewer mammary stem cells, have a lower likelihood of malignant conversion. Fetal growth is regulated by genomically imprinted genes which are in conflict; they promote growth when derived from the father and suppress growth when derived from the mother. The kinship theory explicates that the intensity of conflict between these genes affects growth and therefore the size of the newborn. In descendants of closely related parents, this gene clash is less resulting in a smaller infant. In this review, we elucidate the different mechanisms by which human inbreeding affects BCR, and why this risk is dissimilar in different inbred populations.]]>
Tue, 21 Nov 2017 00:00:00 PST
Enrichment of colorectal cancer associations in functional regions: Insight for using epigenomics data in the analysis of whole genome sequence-imputed GWAS data. Bien SA, Auer PL, Harrison TA, Qu C, Connolly CM, Greenside PG, Chen S, Berndt SI, Bézieau S, Kang HM, Huyghe J, Brenner H, Casey G, Chan AT, Hopper JL, Banbury BL, Chang-Claude J, Chanock SJ, Haile RW, Hoffmeister M, Fuchsberger C, Jenkins MA, Leal SM, Lemire M, Newcomb PA, Gallinger S, Potter JD, Schoen RE, Slattery ML, Smith JD, Le Marchand L, White E, Zanke BW, Abeçasis GR, Carlson CS, Peters U, Nickerson DA, Kundaje A, Hsu L,  
PLoS One (2017)

The evaluation of less frequent genetic variants and their effect on complex disease pose new challenges for genomic research. To investigate whether epigenetic data can be used to inform aggregate rare-variant association methods (RVAM), we assessed whether variants more significantly associated with colorectal cancer (CRC) were preferentially located in non-coding regulatory regions, and whether enrichment was specific to colorectal tissues.]]>
Tue, 21 Nov 2017 00:00:00 PST
Systematic Review of Epigenetic Effects of Pharmacological Agents for Bipolar Disorders. Lockwood LE, Youssef NA
Brain Sci (Nov 2017)

Epigenetic effects of medications are an evolving field of medicine, and can change the landscape of drug development. The aim of this paper is to systematically review the literature of the relationship between common medications used for treatment of bipolar disorders and epigenetic modifications. MedLine/PubMed searches were performed based on pre-specified inclusion criteria from inception to November 2017. Six animal and human studies met the inclusion criteria. These studies examined the epigenetic changes in the main classes of medications that are used in bipolar disorders, namely mood stabilizers and antipsychotics. Although these initial studies have small to moderate sample size, they generally suggest an evolving and accumulating evidence of epigenetic changes that are associated with several of the medications that are used in bipolar I and II disorders. In this manuscript, we describe the specific epigenetic changes that are associated with the medications studied. Of the studies reviewed, five of the six studies revealed epigenetic changes associated with the use of mood stabilizers or antipsychotic medications. This review contributes to future research directions. Further understanding of the complexities of the epigenome and the untangling of the effects and contributions of disease states versus medications is crucial for the future of drug design and the development of new therapeutics. Epigenetic therapeutics hold great promise for complex disease treatment and personalized interventions, including psychiatric diseases.]]>
Tue, 21 Nov 2017 00:00:00 PST
Ensembl 2018. Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, Billis K, Cummins C, Gall A, Girón CG, Gil L, Gordon L, Haggerty L, Haskell E, Hourlier T, Izuogu OG, Janacek SH, Juettemann T, To JK, Laird MR, Lavidas I, Liu Z, Loveland JE, Maurel T, McLaren W, Moore B, Mudge J, Murphy DN, Newman V, Nuhn M, Ogeh D, Ong CK, Parker A, Patricio M, Riat HS, Schuilenburg H, Sheppard D, Sparrow H, Taylor K, Thormann A, Vullo A, Walts B, Zadissa A, Frankish A, Hunt SE, Kostadima M, Langridge N, Martin FJ, Muffato M, Perry E, Ruffier M, Staines DM, Trevanion SJ, Aken BL, Cunningham F, Yates A, Flicek P
Nucleic Acids Res (Nov 2017)

The Ensembl project has been aggregating, processing, integrating and redistributing genomic datasets since the initial releases of the draft human genome, with the aim of accelerating genomics research through rapid open distribution of public data. Large amounts of raw data are thus transformed into knowledge, which is made available via a multitude of channels, in particular our browser (http://www.ensembl.org). Over time, we have expanded in multiple directions. First, our resources describe multiple fields of genomics, in particular gene annotation, comparative genomics, genetics and epigenomics. Second, we cover a growing number of genome assemblies; Ensembl Release 90 contains exactly 100. Third, our databases feed simultaneously into an array of services designed around different use cases, ranging from quick browsing to genome-wide bioinformatic analysis. We present here the latest developments of the Ensembl project, with a focus on managing an increasing number of assemblies, supporting efforts in genome interpretation and improving our browser.]]>
Mon, 20 Nov 2017 00:00:00 PST
ANISEED 2017: extending the integrated ascidian database to the exploration and evolutionary comparison of genome-scale datasets. Brozovic M, Dantec C, Dardaillon J, Dauga D, Faure E, Gineste M, Louis A, Naville M, Nitta KR, Piette J, Reeves W, Scornavacca C, Simion P, Vincentelli R, Bellec M, Aicha SB, Fagotto M, Guéroult-Bellone M, Haeussler M, Jacox E, Lowe EK, Mendez M, Roberge A, Stolfi A, Yokomori R, Brown CT, Cambillau C, Christiaen L, Delsuc F, Douzery E, Dumollard R, Kusakabe T, Nakai K, Nishida H, Satou Y, Swalla B, Veeman M, Volff JN, Lemaire P
Nucleic Acids Res (Nov 2017)

ANISEED (www.aniseed.cnrs.fr) is the main model organism database for tunicates, the sister-group of vertebrates. This release gives access to annotated genomes, gene expression patterns, and anatomical descriptions for nine ascidian species. It provides increased integration with external molecular and taxonomy databases, better support for epigenomics datasets, in particular RNA-seq, ChIP-seq and SELEX-seq, and features novel interactive interfaces for existing and novel datatypes. In particular, the cross-species navigation and comparison is enhanced through a novel taxonomy section describing each represented species and through the implementation of interactive phylogenetic gene trees for 60% of tunicate genes. The gene expression section displays the results of RNA-seq experiments for the three major model species of solitary ascidians. Gene expression is controlled by the binding of transcription factors to cis-regulatory sequences. A high-resolution description of the DNA-binding specificity for 131 Ciona robusta (formerly C. intestinalis type A) transcription factors by SELEX-seq is provided and used to map candidate binding sites across the Ciona robusta and Phallusia mammillata genomes. Finally, use of a WashU Epigenome browser enhances genome navigation, while a Genomicus server was set up to explore microsynteny relationships within tunicates and with vertebrates, Amphioxus, echinoderms and hemichordates.]]>
Fri, 17 Nov 2017 00:00:00 PST
Evolutionary epigenomics of retrotransposon-mediated methylation spreading in rice by. Choi JY, Purugganan MD
Mol Biol Evol (Nov 2017)

Plant genomes contain numerous transposable elements (TEs), and many hypotheses on the evolutionary drivers that restrict TE activity have been postulated. Few models, however, have focused on the evolutionary epigenomic interaction between the plant host and its TE. The host genome recruits epigenetic factors, such as methylation, to silence TEs but methylation can spread beyond the TE sequence and influence the expression of nearby host genes. In this study, we investigated this epigenetic trade-off between TE and proximal host gene silencing by studying the epigenomic regulation of repressing long terminal repeat (LTR) retrotransposons (RTs) in Oryza sativa. Results showed significant evidence of methylation spreading originating from the LTR-RT sequences, and the extent of spreading was dependent on 5 factors: 1) LTR-RT family, 2) time since the LTR-RT insertion, 3) recombination rate of the LTR-RT region, 4) level of LTR-RT sequence methylation, and 5) chromosomal location. Methylation spreading had negative effects by reducing host gene expression, but only on host genes with LTR-RT inserted in its introns. Our results also suggested high levels of LTR-RT methylation might have a role in suppressing TE-mediated deleterious ectopic recombination. In the end, despite the methylation spreading, no strong epigenetic trade-off was detected and majority of LTR-RT may have only minor epigenetic effects on nearby host genes.]]>
Fri, 10 Nov 2017 00:00:00 PST
The Impact of Translational Research in Breast Cancer Care: Can We Improve the Therapeutic Scenario? Perri F, Buono G, Schettini F, Arpino G, Bianco R, Criscitiello C, De Placido S, Giuliano M
Anticancer Agents Med Chem (Nov 2017)

Traditionally, breast cancer (BC) is divided into different immunohistochemically (IHC)-defined subtypes, according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors "omics", including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. It is likely that translational research will have in the near future a significant impact in BC care,, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.]]>
Tue, 07 Nov 2017 00:00:00 PST
Naive pluripotent stem cells as a model for studying human developmental epigenomics: opportunities and limitations. Rugg-Gunn PJ
Epigenomics (Dec 2017)

Mon, 06 Nov 2017 00:00:00 PST
An evaluation of noncoding genome annotation tools through enrichment analysis of 15 genome-wide association studies. Li B, Lu Q, Zhao H
Brief Bioinform (Nov 2017)

Functionally annotating genetic variations is an essential yet challenging topic in human genetics research. As large consortia including ENCODE and Roadmap Epigenomics Project continue to generate high-throughput transcriptomic and epigenomic data, many computational frameworks have been developed to integrate these experimental data to predict functionality of genetic variations in both protein-coding and noncoding regions. Here, we compare a number of recently developed annotation frameworks for noncoding regions through enrichment analysis on genome-wide association studies (GWASs). We also compare several different strategies to quantify enrichment using GWAS summary statistics. Our analyses highlight the importance of jointly modeling context-specific annotations with genome-wide data in providing statistically powerful and biologically interpretable enrichment for complex disease associations. Our findings provide insights into when and how computational genome annotations may benefit future complex disease studies on the genome-wide scale.]]>
Mon, 06 Nov 2017 00:00:00 PST
Parent-of-origin-environment interactions in case-parent triads with or without independent controls. Gjerdevik M, Haaland Ã˜A, Romanowska J, Lie RT, Jugessur A, Gjessing HK
Ann Hum Genet (Nov 2017)

With case-parent triad data, one can frequently deduce parent of origin of the child's alleles. This allows a parent-of-origin (PoO) effect to be estimated as the ratio of relative risks associated with the alleles inherited from the mother and the father, respectively. A possible cause of PoO effects is DNA methylation, leading to genomic imprinting. Because environmental exposures may influence methylation patterns, gene-environment interaction studies should be extended to allow for interactions between PoO effects and environmental exposures (i.e., PoOxE). One should thus search for loci where the environmental exposure modifies the PoO effect. We have developed an extensive framework to analyze PoOxE effects in genome-wide association studies (GWAS), based on complete or incomplete case-parent triads with or without independent control triads. The interaction approach is based on analyzing triads in each exposure stratum using maximum likelihood estimation in a log-linear model. Interactions are then tested applying a Wald-based posttest of parameters across strata. Our framework includes a complete setup for power calculations. We have implemented the models in the R software package Haplin. To illustrate our PoOxE test, we applied the new methodology to top hits from our previous GWAS, assessing whether smoking during the periconceptional period modifies PoO effects on cleft palate only.]]>
Thu, 02 Nov 2017 00:00:00 PDT
Rat embryonic stem cells produce fertile offspring through tetraploid complementation. Li TD, Feng GH, Li YF, Wang M, Mao JJ, Wang JQ, Li X, Wang XP, Qu B, Wang LY, Zhang XX, Wan HF, Cui TT, Wan C, Liu L, Zhao XY, Hu BY, Li W, Zhou Q
Proc Natl Acad Sci U S A (Nov 2017)

Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naïve ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.]]>
Sat, 28 Oct 2017 00:00:00 PDT
Mouse Genetic Analysis of Bone Marrow Stem Cell Niches: Technological Pitfalls, Challenges, and Translational Considerations. Chen KG, Johnson KR, Robey PG
Stem Cell Reports (Nov 2017)

The development of mouse genetic tools has made a significant contribution to the understanding of skeletal and hematopoietic stem cell niches in bone marrow (BM). However, many experimental designs (e.g., selections of marker genes, target vector constructions, and choices of reporter murine strains) have unavoidable technological limitations and bias, which lead to experimental discrepancies, data reproducibility issues, and frequent data misinterpretation. Consequently, there are a number of conflicting views relating to fundamental biological questions, including origins and locations of skeletal and hematopoietic stem cells in the BM. In this report, we systematically unravel complicated data interpretations via comprehensive analyses of technological benefits, pitfalls, and challenges in frequently used mouse models and discuss their translational relevance to human stem cell biology. Particularly, we emphasize the important roles of using large human genomic data-informatics in facilitating genetic analyses of mouse models and resolving existing controversies in mouse and human BM stem cell biology.]]>
Mon, 23 Oct 2017 00:00:00 PDT
Whole Genome DNA Methylation Analysis Using Next-Generation Sequencing (BS-seq). Lin IH
Methods Mol Biol (2018)

Plant methylation is widely evident and has played crucial roles ranging in defining the epi-genome variations during abiotic and biotic stress. Variations in epi-genomic level has observed not only in the symmetrical as well as the non-symmetrical sequences. Plethora of these epi-genomic variations have been widely also demonstrated at the flowering, tissue-specific, and also at developmental stages revealing a strong association of the observed epi-alleles to the physiological state. In the present chapter, epi-genomic analysis of the s has been described with functional workflow and illustrated methodology.]]>
Tue, 17 Oct 2017 00:00:00 PDT
NLRPs, the subcortical maternal complex and genomic imprinting. Monk D, Sanchez-Delgado M, Fisher R
Reproduction (Dec 2017)

Before activation of the embryonic genome, the oocyte provides many of the RNAs and proteins required for the epigenetic reprogramming and the transition to a totipotent state. Targeted disruption of a subset of oocyte-derived transcripts in mice results in early embryonic lethality and cleavage-stage embryonic arrest as highlighted by the members of the subcortical maternal complex (SCMC). Maternal-effect recessive mutations of NLRP7, KHDC3L and NLRP5 in humans are associated with variable reproductive outcomes, biparental hydatidiform moles (BiHM) and widespread multi-locus imprinting disturbances. The precise mechanism of action of these genes is unknown, but the maternal-effect phenomenon suggests a function during early pre-implantation development, while biochemical and genetic studies implement them as SCMC members or interacting partners. In this review article, we discuss the role of the NLRP family members and the SCMC proteins in the establishment of genomic imprints and post-zygotic methylation maintenance, the recent advances made in the understanding of the biology involved in BiHM formation and the wider roles of the SCMC in mammalian reproduction.]]>
Sat, 16 Sep 2017 00:00:00 PDT
Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker. Zadora J, Singh M, Herse F, Przybyl L, Haase N, Golic M, Yung HW, Huppertz B, Cartwright JE, Whitley G, Johnsen GM, Levi G, Isbruch A, Schulz H, Luft FC, Müller DN, Staff AC, Hurst LD, Dechend R, Izsvák Z
Circulation (Nov 2017)

Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia.]]>
Thu, 14 Sep 2017 00:00:00 PDT
'Omics' and endocrine-disrupting chemicals - new paths forward. Messerlian C, Martinez RM, Hauser R, Baccarelli AA
Nat Rev Endocrinol (Dec 2017)

The emerging field of omics - large-scale data-rich biological measurements of the genome - provides new opportunities to advance and strengthen research into endocrine-disrupting chemicals (EDCs). Although some EDCs have been associated with adverse health effects in humans, our understanding of their impact remains incomplete. Progress in the field has been primarily limited by our inability to adequately estimate and characterize exposure and identify sensitive and measurable outcomes during windows of vulnerability. Evolving omics technologies in genomics, epigenomics and mitochondriomics have the potential to generate data that enhance exposure assessment to include the exposome - the totality of the lifetime exposure burden - and provide biology-based estimates of individual risks. Applying omics technologies to expand our knowledge of individual risk and susceptibility will augment biological data in the prediction of variability and response to disease, thereby further advancing EDC research. Together, refined exposure characterization and enhanced disease-risk prediction will help to bridge crucial gaps in EDC research and create opportunities to move the field towards a new vision - precision public health.]]>
Fri, 14 Jul 2017 00:00:00 PDT
Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing. Euskirchen P, Bielle F, Labreche K, Kloosterman WP, Rosenberg S, Daniau M, Schmitt C, Masliah-Planchon J, Bourdeaut F, Dehais C, Marie Y, Delattre JY, Idbaih A
Acta Neuropathol (Nov 2017)

Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e.g., for 1p/19q-codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A, and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within 6 h and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas, and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2, and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations, and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource-restricted settings.]]>
Thu, 22 Jun 2017 00:00:00 PDT
Genetic determinants of low birth weight. Mallia T, Grech A, Hili A, Calleja-Agius J, Pace NP
Minerva Ginecol (Dec 2017)

Birth weight depends on the elaborate interaction between maternal and fetal genotypes, placental function, maternal nutrition and lifestyle and their effect on epigenetic regulators of gene activity. The maternal environment in which the fetus develops is a critical factor in determining birth weight. This review provides an overview of the effect of several genetic variants leading to intrauterine growth restriction and low birth weight. Irrespective of the exact cause of genetic variations of fetal genes, intrauterine growth restriction is most likely due to alteration in the growth hormone and insulin like growth factor axis with distinct changes in the growth factors and their interaction with corresponding receptors. Interactions also occur between the fetal genotype and the intrauterine environment, influencing expression certain genes required for fetal growth. Genomic imprinting is an important mechanism whereby the restraint of fetal growth could be determined through the maternal line. Furthermore, maternal cigarette smoking results in genetic variations in two specific genes, which interact synergistically, resulting in low birth weight. Confined placental mosaicism can also lead to clinically compelling intrauterine growth restriction or even intrauterine fetal death.]]>
Wed, 22 Mar 2017 00:00:00 PDT