Mouse Srpx2 Knockout Project (CRISPR/Cas9)
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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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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. -
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. -
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]. -
Next-Generation DNA Sequencing Identifies Novel Gene Variants And
www.nature.com/scientificreports OPEN Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific Received: 15 November 2016 Accepted: 08 March 2017 language impairment Published: 25 April 2017 Xiaowei Sylvia Chen1, Rose H. Reader2, Alexander Hoischen3, Joris A. Veltman3,4,5, Nuala H. Simpson2, Clyde Francks1,5, Dianne F. Newbury2,6 & Simon E. Fisher1,5 A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential “multiple-hit” cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affectingSTARD9 , while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation. -
What Can Mice Tell Us About Foxp2 Function?
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by MPG.PuRe Available online at www.sciencedirect.com ScienceDirect What can mice tell us about Foxp2 function? 1 2,3 Catherine A French and Simon E Fisher Disruptions of the FOXP2 gene cause a rare speech and Contemporary findings from neurobiology and cognitive language disorder, a discovery that has opened up novel neuroscience indicate that speech and language skills avenues for investigating the relevant neural pathways. depend on the activities of multiple sets of distributed FOXP2 shows remarkably high conservation of sequence neural circuits, both cortical and subcortical. It has been and neural expression in diverse vertebrates, suggesting that proposed that our unique human abilities arose through studies in other species are useful in elucidating its functions. adaptive evolution of pre-existing systems (neural, phys- Here we describe how investigations of mice that carry iological and anatomical) brought together in novel con- disruptions of Foxp2 provide insights at multiple levels: figurations [5,6]. This hypothesis is supported by existing molecules, cells, circuits and behaviour. Work thus far has molecular data. Thus far, genes that have been connected implicated the gene in key processes including neurite to aspects of speech and language have also been found in outgrowth, synaptic plasticity, sensorimotor integration and other species, often with surprisingly deep evolutionary motor-skill learning. histories [5]. Certain aspects of the neural infrastructure Addresses supporting spoken language may be particularly tractable 1 Champalimaud Neuroscience Programme, Champalimaud Centre for for studying in an evolutionary framework. For example, the Unknown, Lisbon, Portugal 2 learning to speak depends crucially on auditory-guided Language and Genetics Department, Max Planck Institute for vocal learning; the acquisition of a vocal repertoire is Psycholinguistics, Nijmegen, The Netherlands 3 based on hearing vocalisations of a conspecific. -
Integration of Molecular Interactome and Targeted Interaction Analysis To
www.nature.com/scientificreports OPEN Integration of Molecular Interactome and Targeted Interaction Analysis to Identify a Received: 2 November 2017 Accepted: 20 August 2018 COPD Disease Network Module Published: xx xx xxxx Amitabh Sharma1,3,4,5, Maksim Kitsak4, Michael H. Cho 1,2,3, Asher Ameli1,10, Xiaobo Zhou1,3, Zhiqiang Jiang1, James D. Crapo6, Terri H. Beaty 7, Jörg Menche8, Per S. Bakke9, Marc Santolini 1,4,5 & Edwin K. Silverman1,2,3 The polygenic nature of complex diseases ofers potential opportunities to utilize network-based approaches that leverage the comprehensive set of protein-protein interactions (the human interactome) to identify new genes of interest and relevant biological pathways. However, the incompleteness of the current human interactome prevents it from reaching its full potential to extract network-based knowledge from gene discovery eforts, such as genome-wide association studies, for complex diseases like chronic obstructive pulmonary disease (COPD). Here, we provide a framework that integrates the existing human interactome information with experimental protein- protein interaction data for FAM13A, one of the most highly associated genetic loci to COPD, to fnd a more comprehensive disease network module. We identifed an initial disease network neighborhood by applying a random-walk method. Next, we developed a network-based closeness approach (CAB) that revealed 9 out of 96 FAM13A interacting partners identifed by afnity purifcation assays were signifcantly close to the initial network neighborhood. Moreover, compared to a similar method (local radiality), the CAB approach predicts low-degree genes as potential candidates. The candidates identifed by the network-based closeness approach were combined with the initial network neighborhood to build a comprehensive disease network module (163 genes) that was enriched with genes diferentially expressed between controls and COPD subjects in alveolar macrophages, lung tissue, sputum, blood, and bronchial brushing datasets. -
Dissecting the Genetics of Human Communication
DISSECTING THE GENETICS OF HUMAN COMMUNICATION: INSIGHTS INTO SPEECH, LANGUAGE, AND READING by HEATHER ASHLEY VOSS-HOYNES Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Epidemiology and Biostatistics CASE WESTERN RESERVE UNIVERSITY January 2017 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We herby approve the dissertation of Heather Ashely Voss-Hoynes Candidate for the degree of Doctor of Philosophy*. Committee Chair Sudha K. Iyengar Committee Member William Bush Committee Member Barbara Lewis Committee Member Catherine Stein Date of Defense July 13, 2016 *We also certify that written approval has been obtained for any proprietary material contained therein Table of Contents List of Tables 3 List of Figures 5 Acknowledgements 7 List of Abbreviations 9 Abstract 10 CHAPTER 1: Introduction and Specific Aims 12 CHAPTER 2: Review of speech sound disorders: epidemiology, quantitative components, and genetics 15 1. Basic Epidemiology 15 2. Endophenotypes of Speech Sound Disorders 17 3. Evidence for Genetic Basis Of Speech Sound Disorders 22 4. Genetic Studies of Speech Sound Disorders 23 5. Limitations of Previous Studies 32 CHAPTER 3: Methods 33 1. Phenotype Data 33 2. Tests For Quantitative Traits 36 4. Analytical Methods 42 CHAPTER 4: Aim I- Genome Wide Association Study 49 1. Introduction 49 2. Methods 49 3. Sample 50 5. Statistical Procedures 53 6. Results 53 8. Discussion 71 CHAPTER 5: Accounting for comorbid conditions 84 1. Introduction 84 2. Methods 86 3. Results 87 4. Discussion 105 CHAPTER 6: Hypothesis driven pathway analysis 111 1. Introduction 111 2. Methods 112 3. Results 116 4. -
Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
G C A T T A C G G C A T genes Article Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability Nekane Ibarluzea 1,2 , Ana Belén de la Hoz 1,2, Olatz Villate 1,2,3, Isabel Llano 1,2,3 , Intzane Ocio 4, Itxaso Martí 5, Miriam Guitart 6, Elisabeth Gabau 6, Fernando Andrade 1,2, Blanca Gener 1,2,3 and María-Isabel Tejada 1,2,3,* 1 Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (N.I.); [email protected] (A.B.d.l.H.); [email protected] (O.V.); [email protected] (I.L.); [email protected] (F.A.); [email protected] (B.G.) 2 Spanish Consortium for Research on Rare Diseases (CIBERER), 28029 Madrid, Spain 3 Genetics Service, Cruces University Hospital, Osakidetza Basque Health Service, 48903 Barakaldo, Spain 4 Department of Paediatric Neurology, Araba University Hospital, Osakidetza Basque Health Service, 01009 Gasteiz, Spain; [email protected] 5 Department of Paediatric Neurology, Donostia University Hospital, Osakidetza Basque Health Service, 20014 Donostia, Spain; [email protected] 6 Genetics Laboratory, Paediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; [email protected] (M.G.); [email protected] (E.G.) * Correspondence: [email protected] Received: 3 December 2019; Accepted: 30 December 2019; Published: 2 January 2020 Abstract: X-linked intellectual disability (XLID) is known to contribute up to 10% of intellectual disability (ID) in males and could explain the increased ratio of affected males observed in patients with ID. -
FOXP2 and Language Alterations in Psychiatric Pathology Salud Mental, Vol
Salud mental ISSN: 0185-3325 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz Castro Martínez, Xochitl Helga; Moltó Ruiz, María Dolores; Morales Marin, Mirna Edith; Flores Lázaro, Julio César; González Fernández, Javier; Gutiérrez Najera, Nora Andrea; Alvarez Amado, Daniel Eduardo; Nicolini Sánchez, José Humberto FOXP2 and language alterations in psychiatric pathology Salud mental, vol. 42, no. 6, 2019, pp. 297-308 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz DOI: 10.17711/SM.0185-3325.2019.039 Available in: http://www.redalyc.org/articulo.oa?id=58262364007 How to cite Complete issue Scientific Information System Redalyc More information about this article Network of Scientific Journals from Latin America and the Caribbean, Spain and Journal's webpage in redalyc.org Portugal Project academic non-profit, developed under the open access initiative REVIEW ARTICLE Volume 42, Issue 6, November-December 2019 doi: 10.17711/SM.0185-3325.2019.039 FOXP2 and language alterations in psychiatric pathology Xochitl Helga Castro Martínez,1 María Dolores Moltó Ruiz,2,3 Mirna Edith Morales Marin,1 Julio César Flores Lázaro,4 Javier González Fernández,2 Nora Andrea Gutiérrez Najera,1 Daniel Eduardo Alvarez Amado,5 José Humberto Nicolini Sánchez1 1 Laboratorio de Genómica de Enfer- ABSTRACT medades Psiquiátricas y Neurode- generativas, Instituto Nacional de From the first reports of the linguist Noam Chomsky it has become clear that the development Medicina Genómica, Ciudad de Background. México, México. of language has an important genetic component. Several reports in families have shown the relationship 2 Departamento de Genética. Univer- between language disorders and genetic polymorphisms. The FOXP2 gene has been a fundamental piece sitat de València. -
Identi Cation of Novel Hub Genes Through Expression Pro Les
Identication of Novel Hub Genes Through Expression Proles Analysis in Adrenocortical Carcinoma Chenhe Yao Beijing Zhicheng Biomedical Technology Co,Ltd Xiaoling Zhao Beijing Zhicheng Biomedical Technology Co,Ltd Xuemeng Shang Beijing Zhicheng Biomedical Technology Co,Ltd Binghan Jia Beijing Zhicheng Biomedical Technology Co,Ltd Shuaijie Dou Beijing Zhicheng Biomedical Technology Co,Ltd Weiliang Ye Beijing Zhicheng Biomedical Technology Co,Ltd Yuemei Yang ( [email protected] ) Beijing Zhicheng Biomedical Technology,Co.,Ltd. Research Keywords: Adrenocortical carcinoma, biomarkers, gene expression proling, Co-expression, prognosis Posted Date: July 1st, 2020 DOI: https://doi.org/10.21203/rs.3.rs-38768/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/21 Abstract Background: Adrenocortical carcinoma (ACC) is a heterogeneous and rare malignant tumor associated with a poor prognosis. The molecular mechanisms of ACC remain elusive and more accurate biomarkers for the prediction of prognosis are needed. Methods: In this study, integrative proling analyses were performed to identify novel hub genes in ACC to provide promising targets for future investigation. Three gene expression proling datasets in the GEO database were used for the identication of overlapped differentially expressed genes (DEGs) following the criteria of adj.P.Value<0.05 and |log2 FC|>0.5 in ACC. Novel hub genes were screened out following a series of processes: the retrieval of DEGs with no known associations with ACC on Pubmed, then the cross-validation of expression values and signicant associations with overall survival in the GEPIA2 and starBase databases, and nally the prediction of gene-tumor association in the GeneCards database. -
Sex Determines the Expression Level of One Third of the Actively Expressed Genes in Bovine Blastocysts
Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts P. Bermejo-Alvareza, D. Rizosa, D. Rathb, P. Lonerganc, and A. Gutierrez-Adana,1 aDepartamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid 28040, Spain; bInstitute of Farm Animal Genetics, Friedrich-Loeffer-Institut, 31535 Neustadt-Mariensee, Germany; and cSchool of Agriculture, Food Science, and Veterinary Medicine, University College Dublin, Dublin 4, Ireland Edited by George Seidel, Colorado State University, and approved January 6, 2010 (received for review December 3, 2009) Although genetically identical for autosomal Chrs (Chr), male and inactivation process and be expressed biallelically. This situation is female preimplantation embryos could display sex-specific transcrip- especially common during preimplantation development, when X tional regulation. To illustrate sex-specific differences at the mRNA inactivation is a reversible dynamic process (11) and may lead to an level, we compared gene-expression patterns between male and up-regulation of X-linked genes in female embryos (2, 3). On the female blastocysts by DNA microarray comparison of nine groups of other hand, male embryos only contain the maternally inherited X- 60 bovine in vitro-produced blastocysts of each sex. Almost one-third Chr; thus, an X-linked gene up-regulation in females may also occur of the transcripts detected showed sexual dimorphism (2,921 tran- as a result of an imprinting mechanism leading to a total or partial scripts; false-discovery rate, P < 0.05), suggesting that in the absence maternal allele transcriptional repression (11). of hormonal influences, the sex Chrs impose an extensive transcrip- Global gene expression analyses in preimplantation embryos tional regulation upon autosomal genes.