Next-Generation Sequencing Identifies Novel Gene Variants and Pathways Involved in Specific Language Impairment
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Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma
Anatomy and Pathology Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma Sarah L. Lake,1 Sarah E. Coupland,1 Azzam F. G. Taktak,2 and Bertil E. Damato3 PURPOSE. To detect deletions and loss of heterozygosity of disease is fatal in 92% of patients within 2 years of diagnosis. chromosome 3 in a rare subset of fatal, disomy 3 uveal mela- Clinical and histopathologic risk factors for UM metastasis noma (UM), undetectable by fluorescence in situ hybridization include large basal tumor diameter (LBD), ciliary body involve- (FISH). ment, epithelioid cytomorphology, extracellular matrix peri- ϩ ETHODS odic acid-Schiff-positive (PAS ) loops, and high mitotic M . Multiplex ligation-dependent probe amplification 3,4 5 (MLPA) with the P027 UM assay was performed on formalin- count. Prescher et al. showed that a nonrandom genetic fixed, paraffin-embedded (FFPE) whole tumor sections from 19 change, monosomy 3, correlates strongly with metastatic death, and the correlation has since been confirmed by several disomy 3 metastasizing UMs. Whole-genome microarray analy- 3,6–10 ses using a single-nucleotide polymorphism microarray (aSNP) groups. Consequently, fluorescence in situ hybridization were performed on frozen tissue samples from four fatal dis- (FISH) detection of chromosome 3 using a centromeric probe omy 3 metastasizing UMs and three disomy 3 tumors with Ͼ5 became routine practice for UM prognostication; however, 5% years’ metastasis-free survival. to 20% of disomy 3 UM patients unexpectedly develop metas- tases.11 Attempts have therefore been made to identify the RESULTS. Two metastasizing UMs that had been classified as minimal region(s) of deletion on chromosome 3.12–15 Despite disomy 3 by FISH analysis of a small tumor sample were found these studies, little progress has been made in defining the key on MLPA analysis to show monosomy 3. -
Supplementary Materials
Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine -
Mitoxplorer, a Visual Data Mining Platform To
mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, Cecilia Garcia-Perez, José Villaveces, Salma Gamal, Giovanni Cardone, Fabiana Perocchi, et al. To cite this version: Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, et al.. mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dy- namics and mutations. Nucleic Acids Research, Oxford University Press, 2020, 10.1093/nar/gkz1128. hal-02394433 HAL Id: hal-02394433 https://hal-amu.archives-ouvertes.fr/hal-02394433 Submitted on 4 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gkz1128 Downloaded from https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkz1128/5651332 by Bibliothèque de l'université la Méditerranée user on 04 December 2019 mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim1,†, Prasanna Koti1,†, Adrien Bonnard2, Fabio Marchiano3, Milena Durrbaum¨ 1, Cecilia Garcia-Perez4, Jose Villaveces1, Salma Gamal1, Giovanni Cardone1, Fabiana Perocchi4, Zuzana Storchova1,5 and Bianca H. -
A Molecular Classification of Human Mesenchymal Stromal Cells Florian Rohart1, Elizabeth Mason1, Nicholas Matigian1, Rowland
bioRxiv preprint doi: https://doi.org/10.1101/024414; this version posted August 11, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Rohart'et'al,'The'MSC'Signature' 1' 1' A Molecular Classification of Human Mesenchymal Stromal Cells 2' Florian Rohart1, Elizabeth Mason1, Nicholas Matigian1, Rowland Mosbergen1, 3' Othmar Korn1, Tyrone Chen1, Suzanne Butcher1, Jatin Patel2, Kerry Atkinson2, 4' Kiarash Khosrotehrani2,3, Nicholas M Fisk2,4, Kim-Anh Lê Cao3 and Christine A 5' Wells1,5* 6' 1 Australian Institute for Bioengineering and Nanotechnology, The University of 7' Queensland, Brisbane, QLD Australia 4072 8' 2 The University of Queensland Centre for Clinical Research, Herston, Brisbane, 9' Queensland, Australia, 4029 10' 3 The University of Queensland Diamantina Institute, Translational Research 11' Institute, Woolloongabba, Brisbane QLD Australia, 4102 12' 4 Centre for Advanced Prenatal Care, Royal Brisbane & Women’s Hospital, Herston, 13' Brisbane, Queensland, Australia, 4029 14' 5 Institute for Infection, Immunity and Inflammation, College of Medical, Veterinary & 15' Life Sciences, The University of Glasgow, Scotland, UK G12 8TA 16' *Correspondence to: Christine Wells, [email protected] 17' bioRxiv preprint doi: https://doi.org/10.1101/024414; this version posted August 11, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
Optic Nerve Crush Induces Spatial and Temporal Gene Expression Patterns
Sharma et al. Molecular Neurodegeneration 2014, 9:14 http://www.molecularneurodegeneration.com/content/9/1/14 RESEARCH ARTICLE Open Access Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice Tasneem P Sharma1,2, Colleen M McDowell1,2, Yang Liu1,2, Alex H Wagner3,4, David Thole3, Benjamin P Faga4, Robert J Wordinger1,2, Terry A Braun3,4 and Abbot F Clark1,2* Abstract Background: Central nervous system (CNS) trauma and neurodegenerative disorders trigger a cascade of cellular and molecular events resulting in neuronal apoptosis and regenerative failure. The pathogenic mechanisms and gene expression changes associated with these detrimental events can be effectively studied using a rodent optic nerve crush (ONC) model. The purpose of this study was to use a mouse ONC model to: (a) evaluate changes in retina and optic nerve (ON) gene expression, (b) identify neurodegenerative pathogenic pathways and (c) discover potential new therapeutic targets. Results: Only 54% of total neurons survived in the ganglion cell layer (GCL) 28 days post crush. Using Bayesian Estimation of Temporal Regulation (BETR) gene expression analysis, we identified significantly altered expression of 1,723 and 2,110 genes in the retina and ON, respectively. Meta-analysis of altered gene expression (≥1.5, ≤-1.5, p < 0.05) using Partek and DAVID demonstrated 28 up and 20 down-regulated retinal gene clusters and 57 up and 41 down-regulated optic nerve clusters. Regulated gene clusters included regenerative change, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. Expression of selected genes (Vsnl1, Syt1, Synpr and Nrn1) from retinal and ON neuronal clusters were quantitatively and qualitatively examined for their relation to axonal neurodegeneration by immunohistochemistry and qRT-PCR. -
Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant
G C A T T A C G G C A T genes Article Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging Hao Xu 1, Yu Jiang 2, Sheng Li 2, Lang Xie 1, Yi-Xi Tao 1 and Yun Li 1,2,* 1 Institute of Three Gorges Ecological Fisheries of Chongqing, College of Fisheries, Southwest University, Chongqing 400715, China; [email protected] (H.X.); [email protected] (L.X.); [email protected] (Y.-X.T.) 2 Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University, Chongqing 400715, China; [email protected] (Y.J.); [email protected] (S.L.) * Correspondence: [email protected]; Tel.: +86-2368-2519-62 Received: 19 August 2020; Accepted: 21 September 2020; Published: 24 September 2020 Abstract: Oxidation resistance gene 1 (OXR1) is essential for protection against oxidative stress in mammals, but its functions in non-mammalian vertebrates, especially in fish, remain uncertain. Here, we created a homozygous oxr1a-knockout zebrafish via the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9) system. Compared with / wild-type (WT) zebrafish, oxr1a− − mutants exhibited higher mortality and more apoptotic cells under oxidative stress, and multiple antioxidant genes (i.e., gpx1b, gpx4a, gpx7 and sod3a) involved in detoxifying cellular reactive oxygen species were downregulated significantly. Based on these observations, we conducted a comparative transcriptome analysis of early oxidative stress response. The results show that oxr1a mutation caused more extensive changes in transcriptional networks / compared to WT zebrafish, and several stress response and pro-inflammatory pathways in oxr1a− − mutant zebrafish were strongly induced. -
Oxr1 Improves Pathogenic Cellular Features of ALS-Associated FUS
Human Molecular Genetics, 2015, Vol. 24, No. 12 3529–3544 doi: 10.1093/hmg/ddv104 Advance Access Publication Date: 19 March 2015 Original Article ORIGINAL ARTICLE Oxr1 improves pathogenic cellular features of ALS-associated FUS and TDP-43 mutations Downloaded from https://academic.oup.com/hmg/article/24/12/3529/623195 by guest on 26 July 2021 Mattéa J. Finelli†, Kevin X. Liu†, Yixing Wu, Peter L. Oliver* and Kay E. Davies* MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK *To whom correspondence should be addressed. Tel: +44 1865285880/79; Email: [email protected] (K.E.D.); [email protected] (P.L.O.) Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neuron-like cells. Mutations in the RNA- and DNA-binding proteins, fused in sarcoma (FUS) and transactive response DNA-binding protein 43 kDa (TDP-43), are responsible for 5–10% of familial and 1% of sporadic ALS cases. Importantly, aggregation of misfolded FUS or TDP- 43 is also characteristic of several neurodegenerative disorders in addition to ALS, including frontotemporal lobar degeneration. Moreover, splicing deregulation of FUS and TDP-43 target genes as well as mitochondrial abnormalities are associated with disease-causing FUS and TDP-43 mutants. While progress has been made to understand the functions of these proteins, the exact mechanisms by which FUS and TDP-43 cause ALS remain unknown. Recently, we discovered that, in addition to being up-regulated in spinal cords of ALS patients, the novel protein oxidative resistance 1 (Oxr1) protects neurons from oxidative stress-induced apoptosis. -
HHS Public Access Author Manuscript
HHS Public Access Author manuscript Author Manuscript Author ManuscriptNature. Author ManuscriptAuthor manuscript; Author Manuscript available in PMC 2015 July 14. Published in final edited form as: Nature. 2014 November 20; 515(7527): 414–418. doi:10.1038/nature13716. Synaptic dysregulation in a human iPS cell model of mental disorders Zhexing Wen1,2,*, Ha Nam Nguyen1,3,*, Ziyuan Guo4,*, Matthew A. Lalli5, Xinyuan Wang1,6, Yijing Su1,2, Nam-Shik Kim1,2, Ki-Jun Yoon1,2, Jaehoon Shin1,3, Ce Zhang1,2, Georgia Makri1,2, David Nauen1,7, Huimei Yu1,2, Elmer Guzman5, Cheng-Hsuan Chiang1,2,8, Nadine Yoritomo9, Kozo Kaibuchi10, Jizhong Zou1,11, Kimberly M. Christian1,2, Linzhao Cheng1,11, Christopher A. Ross3,8,9, Russell L. Margolis3,8,9,§, Gong Chen4,§, Kenneth S. Kosik5,§, Hongjun Song1,2,3,8,§, and Guo-li Ming1,2,3,8,§ 1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 3Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 4Department of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA 5Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, California 93106, USA 6School of Basic Medical Sciences, Fudan University, Shanghai 200032, China 7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA 8The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA Reprints and permissions information is available at www.nature.com/reprints. -
A Widespread Peroxiredoxin-Like Domain Present in Tumor Suppression
Pawłowski et al. BMC Genomics 2010, 11:590 http://www.biomedcentral.com/1471-2164/11/590 RESEARCH ARTICLE Open Access A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins Krzysztof Pawłowski2,4*, Anna Muszewska1, Anna Lenart2, Teresa Szczepińska2, Adam Godzik3, Marcin Grynberg1* Abstract Background: Peroxide turnover and signalling are involved in many biological phenomena relevant to human diseases. Yet, all the players and mechanisms involved in peroxide perception are not known. Elucidating very remote evolutionary relationships between proteins is an approach that allows the discovery of novel protein functions. Here, we start with three human proteins, SRPX, SRPX2 and CCDC80, involved in tumor suppression and progression, which possess a conserved region of similarity. Structure and function prediction allowed the definition of P-DUDES, a phylogenetically widespread, possibly ancient protein structural domain, common to vertebrates and many bacterial species. Results: We show, using bioinformatics approaches, that the P-DUDES domain, surprisingly, adopts the thioredoxin-like (Thx-like) fold. A tentative, more detailed prediction of function is made, namely, that of a 2-Cys peroxiredoxin. Incidentally, consistent overexpression of all three human P-DUDES genes in two public glioblastoma microarray gene expression datasets was discovered. This finding is discussed in the context of the tumor suppressor role that has been ascribed to P-DUDES proteins in several studies. Majority of non-redundant P- DUDES proteins are found in marine metagenome, and among the bacterial species possessing this domain a trend for a higher proportion of aquatic species is observed. Conclusions: The new protein structural domain, now with a broad enzymatic function predicted, may become a drug target once its detailed molecular mechanism of action is understood in detail. -
Transcriptome Analysis of Human OXR1 Depleted Cells Reveals Its Role
www.nature.com/scientificreports OPEN Transcriptome analysis of human OXR1 depleted cells reveals its role in regulating the p53 signaling Received: 28 July 2015 Accepted: 23 October 2015 pathway Published: 30 November 2015 Mingyi Yang1,2, Xiaolin Lin2,5, Alexander Rowe2, Torbjørn Rognes1,3, Lars Eide2 & Magnar Bjørås1,2,4 The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown. We employed RNA sequencing to examine the role of human OXR1 for genome wide transcription regulation. In total, in non-treated and hydrogen peroxide exposed HeLa cells, OXR1 depletion resulted in down-regulation of 554 genes and up-regulation of 253 genes. These differentially expressed genes include transcription factors (i.e. HIF1A, SP6, E2F8 and TCF3), antioxidant genes (PRDX4, PTGS1 and CYGB) and numerous genes of the p53 signaling pathway involved in cell-cycle arrest (i.e. cyclin D, CDK6 and RPRM) and apoptosis (i.e. CytC and CASP9). We demonstrated that OXR1 depleted cells undergo cell cycle arrest in G2/M phase during oxidative stress and increase protein expression of the apoptosis initiator protease CASP9. In summary, OXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species and modulate cell cycle and apoptosis. Reactive oxygen species (ROS) are readily formed in aerobic organisms and constitute a heterogene- ous group comprising superoxide anions, hydrogen peroxide, hydroxyl radicals and other free radicals, which differ in level between compartments inside the cell. In the cell, ROS may attack DNA causing accumulation of oxidative DNA damage and mutations, which are implicated in diseases such as cancer and neurodegeneration1–3. -
Research2007herschkowitzetvolume Al
Open Access Research2007HerschkowitzetVolume al. 8, Issue 5, Article R76 Identification of conserved gene expression features between comment murine mammary carcinoma models and human breast tumors Jason I Herschkowitz¤*†, Karl Simin¤‡, Victor J Weigman§, Igor Mikaelian¶, Jerry Usary*¥, Zhiyuan Hu*¥, Karen E Rasmussen*¥, Laundette P Jones#, Shahin Assefnia#, Subhashini Chandrasekharan¥, Michael G Backlund†, Yuzhi Yin#, Andrey I Khramtsov**, Roy Bastein††, John Quackenbush††, Robert I Glazer#, Powel H Brown‡‡, Jeffrey E Green§§, Levy Kopelovich, reviews Priscilla A Furth#, Juan P Palazzo, Olufunmilayo I Olopade, Philip S Bernard††, Gary A Churchill¶, Terry Van Dyke*¥ and Charles M Perou*¥ Addresses: *Lineberger Comprehensive Cancer Center. †Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ‡Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. reports §Department of Biology and Program in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ¶The Jackson Laboratory, Bar Harbor, ME 04609, USA. ¥Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. #Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA. **Department of Pathology, University of Chicago, Chicago, IL 60637, USA. ††Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. ‡‡Baylor College of Medicine, Houston, TX 77030, USA. §§Transgenic Oncogenesis Group, Laboratory of Cancer Biology and Genetics. Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, MD 20892, USA. Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Section of Hematology/Oncology, Department of Medicine, Committees on Genetics and Cancer Biology, University of Chicago, Chicago, IL 60637, USA. -
The Untold Stories of the Speech Gene, the FOXP2 Cancer Gene
www.Genes&Cancer.com Genes & Cancer, Vol. 9 (1-2), January 2018 The untold stories of the speech gene, the FOXP2 cancer gene Maria Jesus Herrero1,* and Yorick Gitton2,* 1 Center for Neuroscience Research, Children’s National Medical Center, NW, Washington, DC, USA 2 Sorbonne University, INSERM, CNRS, Vision Institute Research Center, Paris, France * Both authors contributed equally to this work Correspondence to: Yorick Gitton, email: [email protected] Keywords: FOXP2 factor, oncogene, cancer, prognosis, language Received: March 01, 2018 Accepted: April 02, 2018 Published: April 18, 2018 Copyright: Herrero and Gitton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT FOXP2 encodes a transcription factor involved in speech and language acquisition. Growing evidence now suggests that dysregulated FOXP2 activity may also be instrumental in human oncogenesis, along the lines of other cardinal developmental transcription factors such as DLX5 and DLX6 [1–4]. Several FOXP family members are directly involved during cancer initiation, maintenance and progression in the adult [5–8]. This may comprise either a pro- oncogenic activity or a deficient tumor-suppressor role, depending upon cell types and associated signaling pathways. While FOXP2 is expressed in numerous cell types, its expression has been found to be down-regulated in breast cancer [9], hepatocellular carcinoma [8] and gastric cancer biopsies [10]. Conversely, overexpressed FOXP2 has been reported in multiple myelomas, MGUS (Monoclonal Gammopathy of Undetermined Significance), several subtypes of lymphomas [5,11], as well as in neuroblastomas [12] and ERG fusion-negative prostate cancers [13].