'; ?> 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 Mon, 24 Oct 2016 03:48:37 PDT Mon, 24 Oct 2016 03:48:37 PDT jirtle@radonc.duke.edu james001@jirtle.com Future of environmental research in the age of epigenomics and exposomics. Holland N
Rev Environ Health (Oct 2016)

Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma. Rapidly evolving methodologies of exposure assessment and the conceptual framework of the Exposome, first introduced in 2005, are new frontiers of environmental research. Metabolomics and adductomics provide remarkable opportunities for a better understanding of exposure and prediction of potential adverse health outcomes. Metabolomics, the study of metabolism at whole-body level, involves assessment of the total repertoire of small molecules present in a biological sample, shedding light on interactions between gene expression, protein expression, and the environment. Advances in genomics, transcriptomics, and epigenomics are generating multidimensional structures of biomarkers of effect and susceptibility, increasingly important for the understanding of molecular mechanisms and the emergence of personalized medicine. Epigenetic mechanisms, particularly DNA methylation and miRNA expression, attract increasing attention as potential links between the genetic and environmental determinants of health and disease. Unlike genetics, epigenetic mechanisms could be reversible and an understanding of their role may lead to better protection of susceptible populations and improved public health.]]>
Fri, 21 Oct 2016 00:00:00 PDT
TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling. Dai HQ, Wang BA, Yang L, Chen JJ, Zhu GC, Sun ML, Ge H, Wang R, Chapman DL, Tang F, Sun X, Xu GL
Nature (Oct 2016)

Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined. Here we show that inactivation of all three Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal signalling. Introduction of a single mutant allele of Nodal in the Tet mutant background partially restored patterning, suggesting that hyperactive Nodal signalling contributes to the gastrulation failure of Tet mutants. Increased Nodal signalling is probably due to diminished expression of the Lefty1 and Lefty2 genes, which encode inhibitors of Nodal signalling. Moreover, reduction in Lefty gene expression is linked to elevated DNA methylation, as both Lefty-Nodal signalling and normal morphogenesis are largely restored in Tet-deficient embryos when the Dnmt3a and Dnmt3b genes are disrupted. Additionally, a point mutation in Tet that specifically abolishes the dioxygenase activity causes similar morphological and molecular abnormalities as the null mutation. Taken together, our results show that TET-mediated oxidation of 5-methylcytosine modulates Lefty-Nodal signalling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B. These findings reveal a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signalling pathways in early body plan formation.]]>
Wed, 19 Oct 2016 00:00:00 PDT
ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing. Chen X, Shen Y, Draper W, Buenrostro JD, Litzenburger U, Cho SW, Satpathy AT, Carter AC, Ghosh RP, East-Seletsky A, Doudna JA, Greenleaf WJ, Liphardt JT, Chang HY
Nat Methods (Oct 2016)

Spatial organization of the genome plays a central role in gene expression, DNA replication, and repair. But current epigenomic approaches largely map DNA regulatory elements outside of the native context of the nucleus. Here we report assay of transposase-accessible chromatin with visualization (ATAC-see), a transposase-mediated imaging technology that employs direct imaging of the accessible genome in situ, cell sorting, and deep sequencing to reveal the identity of the imaged elements. ATAC-see revealed the cell-type-specific spatial organization of the accessible genome and the coordinated process of neutrophil chromatin extrusion, termed NETosis. Integration of ATAC-see with flow cytometry enables automated quantitation and prospective cell isolation as a function of chromatin accessibility, and it reveals a cell-cycle dependence of chromatin accessibility that is especially dynamic in G1 phase. The integration of imaging and epigenomics provides a general and scalable approach for deciphering the spatiotemporal architecture of gene control.]]>
Mon, 17 Oct 2016 00:00:00 PDT
A reporter model to visualize imprinting stability at the Dlk1 locus during mouse development and in pluripotent cells. Swanzey E, Stadtfeld M
Development (Oct 2016)

Genomic imprinting results in the monoallelic expression of genes that encode important regulators of growth and proliferation. Dysregulation of imprinted genes, such as those within the Dlk1-Dio3 locus, is associated with developmental syndromes and specific diseases. Our ability to interrogate causes of imprinting instability has been hindered by the absence of suitable model systems. Here, we describe a Dlk1 knockin reporter mouse that enables single-cell visualization of allele-specific expression and prospective isolation of cells, simultaneously. We show that this "imprinting reporter mouse" can be used to detect tissue-specific Dlk1 expression patterns in developing embryos. We also apply this system to pluripotent cell culture and demonstrate that it faithfully indicates DNA methylation changes induced upon cellular reprogramming. Finally, the reporter system reveals a role of elevated oxygen levels in eroding imprinted Dlk1 expression during prolonged culture and in vitro differentiation. The possibility to study allele-specific expression in different contexts makes our reporter system a useful tool to dissect the regulation of genomic imprinting in normal development and disease.]]>
Wed, 12 Oct 2016 00:00:00 PDT
Expressed alleles of imprinted IGF2, DLK1 and MEG3 colocalize in 3D-preserved nuclei of porcine fetal cells. Lahbib-Mansais Y, Barasc H, Marti-Marimon M, Mompart F, Iannuccelli E, Robelin D, Riquet J, Yerle-Bouissou M
BMC Cell Biol (Oct 2016)

To explore the relationship between spatial genome organization and gene expression in the interphase nucleus, we used a genomic imprinting model, which offers parental-specific gene expression. Using 3D FISH in porcine fetal liver cells, we compared the nuclear organization of the two parental alleles (expressed or not) of insulin-like growth factor 2 (IGF2), a paternally imprinted gene located on chromosome 2. We investigated whether its nuclear positioning favors specific locus associations. We also tested whether IGF2 is implicated in long-range chromatin trans-associations as previously shown in the mouse model species for its reciprocal imprinted gene H19.]]>
Fri, 07 Oct 2016 00:00:00 PDT
Genomic imprinting, disrupted placental expression, and speciation. Brekke TD, Henry LA, Good JM
Evolution (Oct 2016)

The importance of regulatory incompatibilities to the early stages of speciation remains unclear. Hybrid mammals often show extreme parent-of-origin growth effects that are thought to be a consequence of disrupted genetic imprinting (parent-specific epigenetic gene silencing) during early development. Here we test the long-standing hypothesis that abnormal hybrid growth reflects disrupted gene expression due to loss of imprinting (LOI) in hybrid placentas, resulting in dosage imbalances between paternal growth factors and maternal growth repressors. We analyzed placental gene expression in reciprocal dwarf hamster hybrids that show extreme parent-of-origin growth effects relative to their parental species. In massively enlarged hybrid placentas, we observed both extensive transgressive expression of growth-related genes and bi-allelic expression of many genes that were paternally silenced in normal sized hybrids. However, the apparent widespread disruption of paternal silencing was coupled with reduced gene expression levels overall. These patterns are contrary to the predictions of the LOI model and indicate that hybrid misexpression of dosage sensitive genes is caused by other regulatory mechanisms in this system. Collectively, our results support a central role for disrupted gene expression and imprinting in the evolution of mammalian hybrid inviability, but call into question the generality of the widely invoked LOI model. This article is protected by copyright. All rights reserved.]]>
Fri, 07 Oct 2016 00:00:00 PDT
A Synopsis of the "Influence of Epigenetics, Genetics, and Immunology" Session Part A at the 35th Annual Society of Toxicologic Pathology Symposium. Harrill AH, Moggs JG, Adkins KK, Augustin HG, Johnson RC, Leach MW
Toxicol Pathol (Oct 2016)

The overarching theme of the 2016 Society of Toxicology Pathology's Annual Symposium was "The Basis and Relevance of Variation in Toxicologic Responses." Session 4 focused on genetic variation as a potential source for variability in toxicologic responses within nonclinical toxicity studies and further explored how knowledge of genetic traits might enable targeted prospective and retrospective studies in drug development and human health risk assessment. In this session, the influence of both genetic sequence variation and epigenetic modifications on toxicologic responses and their implications for understanding risk were explored. In this overview, the presentations in this session will be summarized, with a goal of exploring the ramifications of genetic and epigenetic variability within and across species for toxicity studies and disseminating information regarding novel tools to harness this variability to advance understanding of toxicologic responses across populations.]]>
Thu, 06 Oct 2016 00:00:00 PDT
Insights in human epigenomic dynamics through comparative primate analysis. Bell CG
Genomics (Oct 2016)

Epigenomic analysis gives a molecular insight into cell-specific genomic activity. It provides a detailed functional plan to dissect an organism, tissue by tissue. Therefore comparative epigenomics may increase understanding of human-acquired traits, by revealing regulatory changes in systems such as the neurological, musculoskeletal, and immunological. Enhancer loci evolve fast by hijacking elements from other tissues or rewiring and amplifying existing units for human-specific function. Promoters by contrast often require a CpG dense genetic infrastructure. Specific interplay occurs between the two, but also a shared modality of function, with coordination from global chromatin-modifying enzymes. Changes in specific transcription factor binding sites also facilitate the local epigenetic state. In the case of CTCF, these may further influence 3-dimensional structure and interaction. How these mechanistic units are modulated between tissue and species enables more comprehensive understanding of human processes and pathology. With this information, precise therapeutic targeting of these epigenetic modifications may become possible.]]>
Wed, 05 Oct 2016 00:00:00 PDT
Establishment and functions of DNA methylation in the germline. Stewart KR, Veselovska L, Kelsey G
Epigenomics (Oct 2016)

Epigenetic modifications established during gametogenesis regulate transcription and other nuclear processes in gametes, but also have influences in the zygote, embryo and postnatal life. This is best understood for DNA methylation which, established at discrete regions of the oocyte and sperm genomes, governs genomic imprinting. In this review, we describe how imprinting has informed our understanding of de novo DNA methylation mechanisms, highlight how recent genome-wide profiling studies have provided unprecedented insights into establishment of the sperm and oocyte methylomes and consider the fate and function of gametic methylation and other epigenetic modifications after fertilization.]]>
Fri, 23 Sep 2016 00:00:00 PDT
Increased dosage of the imprinted Ascl2 gene restrains two key endocrine lineages of the mouse Placenta. Tunster SJ, McNamara GI, Creeth HD, John RM
Dev Biol (Oct 2016)

Imprinted genes are expressed primarily from one parental allele by virtue of a germ line epigenetic process. Achaete-scute complex homolog 2 (Ascl2 aka Mash2) is a maternally expressed imprinted gene that plays a key role in placental and intestinal development. Loss-of-function of Ascl2 results in an expansion of the parietal trophoblast giant cell (P-TGC) lineage, an almost complete loss of Trophoblast specific protein alpha (Tpbpa) positive cells in the ectoplacental cone and embryonic failure by E10.5. Tpbpa expression marks the progenitors of some P-TGCs, two additional trophoblast giant cell lineages (spiral artery and canal), the spongiotrophoblast and the glycogen cell lineage. Using a transgenic model, here we show that elevated expression of Ascl2 reduced the number of P-TGC cells by 40%. Elevated Ascl2 also resulted in a marked loss of the spongiotrophoblast and a substantial mislocalisation of glycogen cells into the labyrinth. In addition, Ascl2-Tg placenta contained considerably more placental glycogen than wild type. Glycogen cells are normally located within the junctional zone in close contact with spongiotrophoblast cells, before migrating through the P-TGC layer into the maternal decidua late in gestation where their stores of glycogen are released. The failure of glycogen cells to release their stores of glycogen may explain both the inappropriate accumulation of glycogen and fetal growth restriction observed late in gestation in this model. In addition, using in a genetic cross we provide evidence that Ascl2 requires the activity of a second maternally expressed imprinted gene, Pleckstrin homology-like domain, family a, member 2 (Phlda2) to limit the expansion of the spongiotrophoblast. This "belts and braces" approach demonstrates the importance of genomic imprinting in regulating the size of the placental endocrine compartment for optimal placental development and fetal growth.]]>
Wed, 21 Sep 2016 00:00:00 PDT
The epigenome in Alzheimer's disease: current state and approaches for a new path to gene discovery and understanding disease mechanism. Klein HU, Bennett DA, De Jager PL
Acta Neuropathol (Oct 2016)

The advent of new technologies and analytic approaches is beginning to provide an unprecedented look at features of the human genome that affect RNA expression. These "epigenomic" features are found in a number of different forms: they include DNA methylation, covalent modifications of histone proteins and non-coding RNAs. Some of these features have now been implicated in Alzheimer's disease (AD). Here, we focus on recent studies that have identified robust observations relating to DNA methylation and chromatin in human brain tissue; these findings will ground the next generation of studies and provide a model for the design of such studies. Stemming from observations that compounds with histone deacetylase activity may be beneficial in AD, epigenome-wide studies in cortical samples from large numbers of human subjects have now shown that AD-associated epigenomic changes are reproducible, are not driven by genetic risk factors, and are widespread at specific locations in the genome. A fundamental question of whether such changes are causal remains to be demonstrated, but it is already clear that well-powered investigations of the human epigenome in the target organ of a neurodegenerative disease are feasible, are implicating new areas of the genome in the disease, and will be an important tool for future studies. We are now at an inflection point: as genome-wide association studies of genetic variants come to an end, a new generation of studies exploring the epigenome will provide an important new layer of information with which to enrich our understanding of AD pathogenesis and to possibly guide development of new therapeutic targets.]]>
Sat, 17 Sep 2016 00:00:00 PDT
Genomic Imprinting in the Endosperm Is Systematically Perturbed in Abortive Hybrid Tomato Seeds. Florez-Rueda AM, Paris M, Schmidt A, Widmer A, Grossniklaus U, Städler T
Mol Biol Evol (Nov 2016)

Hybrid seed failure represents an important postzygotic barrier to interbreeding among species of wild tomatoes (Solanum section Lycopersicon) and other flowering plants. We studied genome-wide changes associated with hybrid seed abortion in the closely related Solanum peruvianum and S. chilense where hybrid crosses yield high proportions of inviable seeds due to endosperm failure and arrested embryo development. Based on differences of seed size in reciprocal hybrid crosses and developmental evidence implicating endosperm failure, we hypothesized that perturbed genomic imprinting is involved in this strong postzygotic barrier. Consequently, we surveyed the transcriptomes of developing endosperms from intra- and inter-specific crosses using tissues isolated by laser-assisted microdissection. We implemented a novel approach to estimate parent-of-origin-specific expression using both homozygous and heterozygous nucleotide differences between parental individuals and identified candidate imprinted genes. Importantly, we uncovered systematic shifts of "normal" (intraspecific) maternal:paternal transcript proportions in hybrid endosperms; the average maternal proportion of gene expression increased in both crossing directions but was stronger with S. peruvianum in the maternal role. These genome-wide shifts almost entirely eliminated paternally expressed imprinted genes in S. peruvianum hybrid endosperm but also affected maternally expressed imprinted genes and all other assessed genes. These profound, systematic changes in parental expression proportions suggest that core processes of transcriptional regulation are functionally compromised in hybrid endosperm and contribute to hybrid seed failure.]]>
Fri, 16 Sep 2016 00:00:00 PDT
Interspecific hybrids of dwarf hamsters and Phasianidae birds as animal models for studying the genetic and developmental basis of hybrid incompatibility. Ishishita S, Matsuda Y
Genes Genet Syst (Oct 2016)

Hybrid incompatibility is important in speciation as it prevents gene flow between closely related populations. Reduced fitness from hybrid incompatibility may also reinforce prezygotic reproductive isolation between sympatric populations. However, the genetic and developmental basis of hybrid incompatibility in higher vertebrates remains poorly understood. Mammals and birds, both amniotes, have similar developmental processes, but marked differences in development such as the XY/ZW sex determination systems and the presence or absence of genomic imprinting. Here, we review the sterile phenotype of hybrids between the Phodopus dwarf hamsters P. campbelli and P. sungorus, and the inviable phenotype of hybrids between two birds of the family Phasianidae, chicken (Gallus gallus domesticus) and Japanese quail (Coturnix japonica). We propose hypotheses for developmental defects that are associated with these hybrid incompatibilities. In addition, we discuss the genetic and developmental basis for these defects in conjunction with recent findings from mouse and avian models of genetics, reproductive biology and genomics. We suggest that these hybrids are ideal animal models for studying the genetic and developmental basis of hybrid incompatibility in amniotes.]]>
Thu, 15 Sep 2016 00:00:00 PDT
Methods of epigenome editing for probing the function of genomic imprinting. Rienecker KD, Hill MJ, Isles AR
Epigenomics (Oct 2016)

The curious patterns of imprinted gene expression draw interest from several scientific disciplines to the functional consequences of genomic imprinting. Methods of probing the function of imprinting itself have largely been indirect and correlational, relying heavily on conventional transgenics. Recently, the burgeoning field of epigenome editing has provided new tools and suggested strategies for asking causal questions with site specificity. This perspective article aims to outline how these new methods may be applied to questions of functional imprinting and, with this aim in mind, to suggest new dimensions for the expansion of these epigenome-editing tools.]]>
Wed, 14 Sep 2016 00:00:00 PDT
Parental Genome Imbalance Causes Post-Zygotic Seed Lethality and Deregulates Imprinting in Rice. Zhang HY, Luo M, Johnson SD, Zhu XW, Liu L, Huang F, Liu YT, Xu PZ, Wu XJ
Rice (N Y) (Dec 2016)

Reproductive isolation between rice of different ploidy levels is manifested as endosperm and embryo abortion in seeds produced by interploidy crosses. Genomic imprinting is considered to be the underlying mechanism establishing the post-zygotic hybridization barrier. We characterized disrupted seed development in reciprocal crosses between a diploid Japonica rice and a tetraploid Indica rice.]]>
Mon, 29 Aug 2016 00:00:00 PDT
A modified MS-PCR approach to diagnose patients with Prader-Willi and Angelman syndrome. Dos Santos JF, Mota LR, Rocha PH, Ferreira de Lima RL
Mol Biol Rep (Nov 2016)

Prader-Willi (PWS) and Angelman (AS) syndromes are clinically distinct neurodevelopmental genetic diseases with multiple phenotypic manifestations. They are one of the most common genetic syndromes caused by non-Mendelian inheritance in the form of genomic imprinting, and can be attributable to the loss of gene expression due to imprinting within the chromosomal region 15q11-q13. Clinical diagnosis of PWS and AS is challenging, and the use of molecular and cytomolecular studies is recommended to help in determining the diagnosis of these conditions. The methylation analysis is a sensible approach; however there are several techniques for this purpose, such as the methylation-sensitive polymerase chain reaction (MS-PCR). This study aims to optimize the MS-PCR assay for the diagnosis of potential PWS and AS patients using DNA modified by sodium bisulfite. We used the MS-PCR technique of PCR described by Kosaki et al. (1997) adapted with betaine. All different concentrations of betaine used to amplify the methylated and unmethylated chromosomal region 15q11-q13 on the gene SNRPN showed amplification results, which increased proportionally to the concentration of betaine. The methylation analysis is a technically robust and reproducible screening method for PWS and AS. The MS-PCR assures a faster, cheaper and more efficient method for the primary diagnosis of the SNRPN gene in cases with PWS and AS, and may detect all of the three associated genetic abnormalities: deletion, uniparental disomy or imprinting errors.]]>
Thu, 18 Aug 2016 00:00:00 PDT
Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases. Li Y, Kellis M
Nucleic Acids Res (Oct 2016)

Genome wide association studies (GWAS) provide a powerful approach for uncovering disease-associated variants in human, but fine-mapping the causal variants remains a challenge. This is partly remedied by prioritization of disease-associated variants that overlap GWAS-enriched epigenomic annotations. Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations. In simulation, RiVIERA promising power in detecting causal variants and causal annotations, the multi-trait joint inference further improved the detection power. We applied RiVIERA to model the existing GWAS summary statistics of 9 autoimmune diseases and Schizophrenia by jointly harnessing the potential causal enrichments among 848 tissue-specific epigenomics annotations from ENCODE/Roadmap consortium covering 127 cell/tissue types and 8 major epigenomic marks. RiVIERA identified meaningful tissue-specific enrichments for enhancer regions defined by H3K4me1 and H3K27ac for Blood T-Cell specifically in the nine autoimmune diseases and Brain-specific enhancer activities exclusively in Schizophrenia. Moreover, the variants from the 95% credible sets exhibited high conservation and enrichments for GTEx whole-blood eQTLs located within transcription-factor-binding-sites and DNA-hypersensitive-sites. Furthermore, joint modeling the nine immune traits by simultaneously inferring and exploiting the underlying epigenomic correlation between traits further improved the functional enrichments compared to single-trait models.]]>
Wed, 13 Jul 2016 00:00:00 PDT
Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14. Martinez ME, Cox DF, Youth BP, Hernandez A
Eur J Hum Genet (Nov 2016)

Individuals with uniparental disomy of chromosome 14 (Temple and Kagami-Ogata syndromes) exhibit a number of developmental abnormalities originating, in part, from aberrant developmental expression of imprinted genes in the DLK1-DIO3 cluster. Although genomic imprinting has been reported in humans for some genes in the cluster, little evidence is available about the imprinting status of DIO3, which modulates developmental exposure to thyroid hormones. We used pyrosequencing to evaluate allelic expression of DLK1 and DIO3 in cDNAs prepared from neonatal foreskins carrying single-nucleotide polymorphisms (SNPs) in the exonic sequence of those genes, and hot-stop PCR to quantify DIO3 allelic expression in cDNA obtained from a skin specimen collected from an adult individual with known parental origin of the DIO3 SNP. In neonatal skin, DLK1 and DIO3 both exhibited a high degree of monoallelic expression from the paternal allele. In the adult skin sample, the allele preferentially expressed is that inherited from the mother, although a different, larger DIO3 mRNA transcript appears the most abundant at this stage. We conclude that DIO3 is an imprinted gene in humans, suggesting that alterations in thyroid hormone exposure during development may partly contribute to the phenotypes associated with uniparental disomy of chromosome 14.]]>
Wed, 22 Jun 2016 00:00:00 PDT
Separating the wheat from the chaff: systematic identification of functionally relevant noncoding variants in ADHD. Tong JH, Hawi Z, Dark C, Cummins TD, Johnson BP, Newman DP, Lau R, Vance A, Heussler HS, Matthews N, Bellgrove MA, Pang KC
Mol Psychiatry (Nov 2016)

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition with negative lifetime outcomes. Uncovering its genetic architecture should yield important insights into the neurobiology of ADHD and assist development of novel treatment strategies. Twenty years of candidate gene investigations and more recently genome-wide association studies have identified an array of potential association signals. In this context, separating the likely true from false associations ('the wheat' from 'the chaff') will be crucial for uncovering the functional biology of ADHD. Here, we defined a set of 2070 DNA variants that showed evidence of association with ADHD (or were in linkage disequilibrium). More than 97% of these variants were noncoding, and were prioritised for further exploration using two tools-genome-wide annotation of variants (GWAVA) and Combined Annotation-Dependent Depletion (CADD)-that were recently developed to rank variants based upon their likely pathogenicity. Capitalising on recent efforts such as the Encyclopaedia of DNA Elements and US National Institutes of Health Roadmap Epigenomics Projects to improve understanding of the noncoding genome, we subsequently identified 65 variants to which we assigned functional annotations, based upon their likely impact on alternative splicing, transcription factor binding and translational regulation. We propose that these 65 variants, which possess not only a high likelihood of pathogenicity but also readily testable functional hypotheses, represent a tractable shortlist for future experimental validation in ADHD. Taken together, this study brings into sharp focus the likely relevance of noncoding variants for the genetic risk associated with ADHD, and more broadly suggests a bioinformatics approach that should be relevant to other psychiatric disorders.]]>
Tue, 26 Apr 2016 00:00:00 PDT
High-throughput «Omics» technologies: New tools for the study of triple-negative breast cancer. Judes G, Rifaï K, Daures M, Dubois L, Bignon YJ, Penault-Llorca F, Bernard-Gallon D
Cancer Lett (Nov 2016)

Triple negative breast cancer (TNBC) represents about 15% to 20% of all breast cancers and is typically associated with poorer outcome than other breast cancer subtypes. The heterogeneity of this breast cancer subtype and present lack of clinically established targeted therapies further complicates treatment of patients. The treatment of TNBC emphasizes enhancing health care and developing personalized medicine. To respond to this need, the researchers have turned their attention to a different approach to scientific enquiry: the era of "big biology" and the integrative study of biological systems, also called "Omics" technologies. The term omics comprises different fields of molecular studies and characterizes a global view on biological molecules such as DNA, RNA, proteins, and metabolites. Combined "omics" approach offers a major tool for the understanding of a challenging cancer model, TNBC. This review discusses the different discoveries made using omics technologies concerning the molecular mechanisms underlying TNBC phenotypic heterogeneity, and their potential transfer to clinical applications.]]>
Fri, 01 Apr 2016 00:00:00 PDT