Genome-Wide Association Study Identifies Multiple Susceptibility Loci
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HEXIM1 (D5Y5K) Rabbit
HEXIM1 (D5Y5K) Rabbit mAb Store at -20°C 3 n 100 µl Orders n 877-616-CELL (2355) (10 western blots) [email protected] Support n 877-678-TECH (8324) [email protected] Web n www.cellsignal.com rev. 01/05/15 #12604 For Research Use Only. Not For Use In Diagnostic Procedures. Entrez-Gene ID #10614 UniProt ID #O94992 Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 Applications Species Cross-Reactivity* Molecular Wt. Isotype mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% W, IP, IF-IC H, Mk 60 kDa Rabbit IgG** sodium azide. Store at –20°C. Do not aliquot the antibody. Endogenous *Species cross-reactivity is determined by western blot. Background: Hexamethylene bis-acetamide-inducible ** Anti-rabbit secondary antibodies must be used to protein 1 (HEXIM1) was originally identified in vascular kDa HeLa A-431 Hep G2 COS-7 detect this antibody. smooth muscle cells as a protein that is upregulated upon 200 Recommended Antibody Dilutions: treatment with the differentiating agent hexamethylene bi- 140 Western blotting 1:1000 sacetamide (1). HEXIM1 binds 7SK RNA, a highly abundant 100 Immunoprecipitation 1:100 non-coding RNA, and together they act as a potent inhibitor 80 Immunofluorescence (IF-IC) 1:1200 of positive transcription elongation factor b (P-TEFb) (2,3). 60 HEXIM1 P-TEFb phosphorylates the C-terminal domain of the largest 50 For product specific protocols please see the web page subunit of RNA polymerase II and is an important regulator for this product at www.cellsignal.com. 40 of transcription elongation (4-8). -
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. -
Expression Patterns of Slit and Robo Family Members in Adult Mouse Spinal Cord and Peripheral Nervous System
RESEARCH ARTICLE Expression patterns of Slit and Robo family members in adult mouse spinal cord and peripheral nervous system Lauren Carr1, David B. Parkinson1, Xin-peng Dun1,2* 1 Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, Devon, United Kingdom, 2 Hubei University of Science and Technology, Xian-Ning City, Hubei, China a1111111111 * [email protected] a1111111111 a1111111111 a1111111111 Abstract a1111111111 The secreted glycoproteins, Slit1-3, are classic axon guidance molecules that act as repul- sive cues through their well characterised receptors Robo1-2 to allow precise axon pathfind- ing and neuronal migration. The expression patterns of Slit1-3 and Robo1-2 have been OPEN ACCESS most characterized in the rodent developing nervous system and the adult brain, but little is Citation: Carr L, Parkinson DB, Dun X-p (2017) known about their expression patterns in the adult rodent peripheral nervous system. Here, Expression patterns of Slit and Robo family we report a detailed expression analysis of Slit1-3 and Robo1-2 in the adult mouse sciatic members in adult mouse spinal cord and nerve as well as their expression in the nerve cell bodies within the ventral spinal cord peripheral nervous system. PLoS ONE 12(2): (motor neurons) and dorsal root ganglion (sensory neurons). Our results show that, in the e0172736. doi:10.1371/journal.pone.0172736 adult mouse peripheral nervous system, Slit1-3 and Robo1-2 are expressed in the cell bod- Editor: Thomas H Gillingwater, University of ies and axons of both motor and sensory neurons. While Slit1 and Robo2 are only Edinburgh, UNITED KINGDOM expressed in peripheral axons and their cell bodies, Slit2, Slit3 and Robo1 are also Received: November 14, 2016 expressed in satellite cells of the dorsal root ganglion, Schwann cells and fibroblasts of Accepted: February 8, 2017 peripheral nerves. -
DE-Kupl: Exhaustive Capture of Biological Variation in RNA-Seq Data Through K-Mer Decomposition
Audoux et al. Genome Biology (2017) 18:243 DOI 10.1186/s13059-017-1372-2 METHOD Open Access DE-kupl: exhaustive capture of biological variation in RNA-seq data through k-mer decomposition Jérôme Audoux1, Nicolas Philippe2,3, Rayan Chikhi4, Mikaël Salson4, Mélina Gallopin5, Marc Gabriel5,6, Jérémy Le Coz5,EmilieDrouineau5, Thérèse Commes1,2 and Daniel Gautheret5,6* Abstract We introduce a k-mer-based computational protocol, DE-kupl, for capturing local RNA variation in a set of RNA-seq libraries, independently of a reference genome or transcriptome. DE-kupl extracts all k-mers with differential abundance directly from the raw data files. This enables the retrieval of virtually all variation present in an RNA-seq data set. This variation is subsequently assigned to biological events or entities such as differential long non-coding RNAs, splice and polyadenylation variants, introns, repeats, editing or mutation events, and exogenous RNA. Applying DE-kupl to human RNA-seq data sets identified multiple types of novel events, reproducibly across independent RNA-seq experiments. Background diversity is genomic variation. Polymorphism and struc- Successive generations of RNA-sequencing technologies tural variations within transcribed regions produce RNAs have bolstered the notion that organisms produce a highly with single-nucleotide variations (SNVs), tandem dupli- diverse and adaptable set of RNA molecules. Modern cations or deletions, transposon integrations, unstable transcript catalogs, such as GENCODE [1], now include microsatellites, or fusion events. These events are major hundreds of thousands of transcripts, reflecting pervasive sources of transcript variation that can strongly impact transcription and widespread alternative RNA processing. RNA processing, transport, and coding potential. -
Transcriptional Mechanisms of Resistance to Anti-PD-1 Therapy
Author Manuscript Published OnlineFirst on February 13, 2017; DOI: 10.1158/1078-0432.CCR-17-0270 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Transcriptional mechanisms of resistance to anti-PD-1 therapy Maria L. Ascierto1, Alvin Makohon-Moore2, 11, Evan J. Lipson1, Janis M. Taube3,4, Tracee L. McMiller5, Alan E. Berger6, Jinshui Fan6, Genevieve J. Kaunitz3, Tricia R. Cottrell4, Zachary A. Kohutek7, Alexander Favorov8,10, Vladimir Makarov7,11, Nadeem Riaz7,11, Timothy A. Chan7,11, Leslie Cope8, Ralph H. Hruban4,9, Drew M. Pardoll1, Barry S. Taylor11,12,13, David B. Solit13, Christine A Iacobuzio-Donahue2,11, and Suzanne L. Topalian5 From the 1Departments of Oncology, 3Dermatology, 4Pathology, 5Surgery, 6The Lowe Family Genomics Core, 8Oncology Bioinformatics Core, and the 9 Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287; the 10Laboratory of System Biology and Computational Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia; and 2Pathology, 7Radiation Oncology, 11Human Oncology and Pathogenesis Program, 12Department of Epidemiology and Biostatistics, and the 13Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York NY 10065. MLA, AM-M, EJL, and JMT contributed equally to this work Running title: Transcriptional mechanisms of resistance to anti-PD-1 Key Words: melanoma, cancer genetics, immunotherapy, anti-PD-1 Financial Support: This study was supported by the Melanoma Research Alliance (to SLT and CI-D), the Bloomberg~Kimmel Institute for Cancer Immunotherapy (to JMT, DMP, and SLT), the Barney Family Foundation (to SLT), Moving for Melanoma of Delaware (to SLT), the 1 Downloaded from clincancerres.aacrjournals.org on October 2, 2021. -
MUC4/MUC16/Muc20high Signature As a Marker of Poor Prognostic for Pancreatic, Colon and Stomach Cancers
Jonckheere and Van Seuningen J Transl Med (2018) 16:259 https://doi.org/10.1186/s12967-018-1632-2 Journal of Translational Medicine RESEARCH Open Access Integrative analysis of the cancer genome atlas and cancer cell lines encyclopedia large‑scale genomic databases: MUC4/MUC16/ MUC20 signature is associated with poor survival in human carcinomas Nicolas Jonckheere* and Isabelle Van Seuningen* Abstract Background: MUC4 is a membrane-bound mucin that promotes carcinogenetic progression and is often proposed as a promising biomarker for various carcinomas. In this manuscript, we analyzed large scale genomic datasets in order to evaluate MUC4 expression, identify genes that are correlated with MUC4 and propose new signatures as a prognostic marker of epithelial cancers. Methods: Using cBioportal or SurvExpress tools, we studied MUC4 expression in large-scale genomic public datasets of human cancer (the cancer genome atlas, TCGA) and cancer cell line encyclopedia (CCLE). Results: We identifed 187 co-expressed genes for which the expression is correlated with MUC4 expression. Gene ontology analysis showed they are notably involved in cell adhesion, cell–cell junctions, glycosylation and cell signal- ing. In addition, we showed that MUC4 expression is correlated with MUC16 and MUC20, two other membrane-bound mucins. We showed that MUC4 expression is associated with a poorer overall survival in TCGA cancers with diferent localizations including pancreatic cancer, bladder cancer, colon cancer, lung adenocarcinoma, lung squamous adeno- carcinoma, skin cancer and stomach cancer. We showed that the combination of MUC4, MUC16 and MUC20 signature is associated with statistically signifcant reduced overall survival and increased hazard ratio in pancreatic, colon and stomach cancer. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Essential Genes and Their Role in Autism Spectrum Disorder
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Essential Genes And Their Role In Autism Spectrum Disorder Xiao Ji University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, and the Genetics Commons Recommended Citation Ji, Xiao, "Essential Genes And Their Role In Autism Spectrum Disorder" (2017). Publicly Accessible Penn Dissertations. 2369. https://repository.upenn.edu/edissertations/2369 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2369 For more information, please contact [email protected]. Essential Genes And Their Role In Autism Spectrum Disorder Abstract Essential genes (EGs) play central roles in fundamental cellular processes and are required for the survival of an organism. EGs are enriched for human disease genes and are under strong purifying selection. This intolerance to deleterious mutations, commonly observed haploinsufficiency and the importance of EGs in pre- and postnatal development suggests a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication and repetitive behavior. More and more genetic evidence points to a polygenic model of ASD and it is estimated that hundreds of genes contribute to ASD. The central question addressed in this dissertation is whether genes with a strong effect on survival and fitness (i.e. EGs) play a specific oler in ASD risk. I compiled a comprehensive catalog of 3,915 mammalian EGs by combining human orthologs of lethal genes in knockout mice and genes responsible for cell-based essentiality. -
Inhibition of SNW1 Association with Spliceosomal Proteins Promotes
Cancer Medicine Open Access ORIGINAL RESEARCH Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells Naoki Sato1, Masao Maeda2, Mai Sugiyama2, Satoko Ito2, Toshinori Hyodo2, Akio Masuda3, Nobuyuki Tsunoda1, Toshio Kokuryo1, Michinari Hamaguchi2, Masato Nagino1 & Takeshi Senga2 1Department of Surgical Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan 2Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan 3Division of Neurogenetics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan Keywords Abstract Apoptosis, EFTUD2, PRPF8, RNA splicing, SNRNP200, SNW1 RNA splicing is a fundamental process for protein synthesis. Recent studies have reported that drugs that inhibit splicing have cytotoxic effects on various Correspondence tumor cell lines. In this report, we demonstrate that depletion of SNW1, a Takeshi Senga, 65 Tsurumai, Showa, Nagoya component of the spliceosome, induces apoptosis in breast cancer cells. Proteo- 466-8550, Japan. Tel: 81-52-744-2463; mics and biochemical analyses revealed that SNW1 directly associates with Fax: 81-52-744-2464; other spliceosome components, including EFTUD2 (Snu114) and SNRNP200 E-mail: [email protected] (Brr2). The SKIP region of SNW1 interacted with the N-terminus of EFTUD2 Funding Information as well as two independent regions in the C-terminus of SNRNP200. Similar to This research was funded by a grant from SNW1 depletion, knockdown of EFTUD2 increased the numbers of apoptotic the Ministry of Education, Culture, Sports, cells. Furthermore, we demonstrate that exogenous expression of either the Science and Technology of Japan SKIP region of SNW1 or the N-terminus region of EFTUD2 significantly pro- (Nanomedicine molecular science, 23107010. -
Noelia Díaz Blanco
Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr. -
SHROOM3 Is a Novel Candidate for Heterotaxy Identified by Whole Exome Sequencing Tariq Et Al
SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing Tariq et al. Tariq et al. Genome Biology 2011, 12:R91 http://genomebiology.com/2011/12/9/R91 (21 September 2011) Tariq et al. Genome Biology 2011, 12:R91 http://genomebiology.com/2011/12/9/R91 RESEARCH Open Access SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing Muhammad Tariq1, John W Belmont2, Seema Lalani2, Teresa Smolarek3 and Stephanie M Ware1,3* Abstract Background: Heterotaxy-spectrum cardiovascular disorders are challenging for traditional genetic analyses because of clinical and genetic heterogeneity, variable expressivity, and non-penetrance. In this study, high-resolution SNP genotyping and exon-targeted array comparative genomic hybridization platforms were coupled to whole-exome sequencing to identify a novel disease candidate gene. Results: SNP genotyping identified absence-of-heterozygosity regions in the heterotaxy proband on chromosomes 1, 4, 7, 13, 15, 18, consistent with parental consanguinity. Subsequently, whole-exome sequencing of the proband identified 26,065 coding variants, including 18 non-synonymous homozygous changes not present in dbSNP132 or 1000 Genomes. Of these 18, only 4 - one each in CXCL2, SHROOM3, CTSO, RXFP1 - were mapped to the absence-of- heterozygosity regions, each of which was flanked by more than 50 homozygous SNPs, confirming recessive segregation of mutant alleles. Sanger sequencing confirmed the SHROOM3 homozygous missense mutation and it was predicted as pathogenic by four bioinformatic tools. SHROOM3 has been identified as a central regulator of morphogenetic cell shape changes necessary for organogenesis and can physically bind ROCK2, a rho kinase protein required for left-right patterning. -
Core Circadian Clock Transcription Factor BMAL1 Regulates Mammary Epithelial Cell
bioRxiv preprint doi: https://doi.org/10.1101/2021.02.23.432439; this version posted February 23, 2021. 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 4.0 International license. 1 Title: Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell 2 growth, differentiation, and milk component synthesis. 3 Authors: Theresa Casey1ǂ, Aridany Suarez-Trujillo1, Shelby Cummings1, Katelyn Huff1, 4 Jennifer Crodian1, Ketaki Bhide2, Clare Aduwari1, Kelsey Teeple1, Avi Shamay3, Sameer J. 5 Mabjeesh4, Phillip San Miguel5, Jyothi Thimmapuram2, and Karen Plaut1 6 Affiliations: 1. Department of Animal Science, Purdue University, West Lafayette, IN, USA; 2. 7 Bioinformatics Core, Purdue University; 3. Animal Science Institute, Agriculture Research 8 Origination, The Volcani Center, Rishon Letsiyon, Israel. 4. Department of Animal Sciences, 9 The Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of 10 Jerusalem, Rehovot, Israel. 5. Genomics Core, Purdue University 11 Grant support: Binational Agricultural Research Development (BARD) Research Project US- 12 4715-14; Photoperiod effects on milk production in goats: Are they mediated by the molecular 13 clock in the mammary gland? 14 ǂAddress for correspondence. 15 Theresa M. Casey 16 BCHM Room 326 17 175 South University St. 18 West Lafayette, IN 47907 19 Email: [email protected] 20 Phone: 802-373-1319 21 22 bioRxiv preprint doi: https://doi.org/10.1101/2021.02.23.432439; this version posted February 23, 2021. 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.