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Sequence Overlap Between Autosomal and Sex-Linked Probes on the Illumina Humanmethylation27 Microarray
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Genomics 97 (2011) 214–222 Contents lists available at ScienceDirect Genomics journal homepage: www.elsevier.com/locate/ygeno Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray Yi-an Chen a,b, Sanaa Choufani a, Jose Carlos Ferreira a,b, Daria Grafodatskaya a, Darci T. Butcher a, Rosanna Weksberg a,b,⁎ a Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada b Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada article info abstract Article history: The Illumina Infinium HumanMethylation27 BeadChip (Illumina 27k) microarray is a high-throughput Received 12 August 2010 platform capable of interrogating the human DNA methylome. In a search for autosomal sex-specific DNA Accepted 18 December 2010 methylation using this microarray, we discovered autosomal CpG loci showing significant methylation Available online 4 January 2011 differences between the sexes. However, we found that the majority of these probes cross-reacted with sequences from sex chromosomes. Moreover, we determined that 6–10% of the microarray probes are non- Keywords: specific and map to highly homologous genomic sequences. Using probes targeting different CpGs that are Illumina Infinium HumanMethylation 27 BeadChip exact duplicates of each other, we investigated the precision of these repeat measurements and concluded Non-specific cross-reactive probe that the overall precision of this microarray is excellent. In addition, we identified a small number of probes Sex-specific DNA methylation targeting CpGs that include single-nucleotide polymorphisms. -
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. -
Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways
biomolecules Article Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways Aayushi Srivastava 1,2,3,4 , Abhishek Kumar 1,5,6 , Sara Giangiobbe 1, Elena Bonora 7, Kari Hemminki 1, Asta Försti 1,2,3 and Obul Reddy Bandapalli 1,2,3,* 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany; [email protected] (A.S.); [email protected] (A.K.); [email protected] (S.G.); [email protected] (K.H.); [email protected] (A.F.) 2 Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany 3 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany 4 Medical Faculty, Heidelberg University, D-69120 Heidelberg, Germany 5 Institute of Bioinformatics, International Technology Park, Bangalore 560066, India 6 Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India 7 S.Orsola-Malphigi Hospital, Unit of Medical Genetics, 40138 Bologna, Italy; [email protected] * Correspondence: [email protected]; Tel.: +49-6221-42-1709 Received: 29 August 2019; Accepted: 10 October 2019; Published: 13 October 2019 Abstract: Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family. -
Host Cell Factors Necessary for Influenza a Infection: Meta-Analysis of Genome Wide Studies
Host Cell Factors Necessary for Influenza A Infection: Meta-Analysis of Genome Wide Studies Juliana S. Capitanio and Richard W. Wozniak Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta Abstract: The Influenza A virus belongs to the Orthomyxoviridae family. Influenza virus infection occurs yearly in all countries of the world. It usually kills between 250,000 and 500,000 people and causes severe illness in millions more. Over the last century alone we have seen 3 global influenza pandemics. The great human and financial cost of this disease has made it the second most studied virus today, behind HIV. Recently, several genome-wide RNA interference studies have focused on identifying host molecules that participate in Influen- za infection. We used nine of these studies for this meta-analysis. Even though the overlap among genes identified in multiple screens was small, network analysis indicates that similar protein complexes and biological functions of the host were present. As a result, several host gene complexes important for the Influenza virus life cycle were identified. The biological function and the relevance of each identified protein complex in the Influenza virus life cycle is further detailed in this paper. Background and PA bound to the viral genome via nucleoprotein (NP). The viral core is enveloped by a lipid membrane derived from Influenza virus the host cell. The viral protein M1 underlies the membrane and anchors NEP/NS2. Hemagglutinin (HA), neuraminidase Viruses are the simplest life form on earth. They parasite host (NA), and M2 proteins are inserted into the envelope, facing organisms and subvert the host cellular machinery for differ- the viral exterior. -
Bioinformatics Mining of the Dark Matter Proteome For
BIOINFORMATICS MINING OF THE DARK MATTER PROTEOME FOR CANCER TARGETS DISCOVERY by Ana Paula Delgado A Thesis Submitted to the Faculty of The Charles E. Schmidt College of Science In Partial Fulfillment of the Requirements for the Degree of Master of Science Florida Atlantic University Boca Raton, Florida May 2015 Copyright 2015 by Ana Paula Delgado ii ACKNOWLEDGEMENTS I would first like to thank Dr. Narayanan for his continuous encouragement, guidance, and support during the past two years of my graduate education. It has truly been an unforgettable experience working in his laboratory. I also want to express gratitude to my external advisor Professor Van de Ven from the University of Leuven, Belgium for his constant involvement and assistance on my project. Moreover, I would like to thank Dr. Binninger and Dr. Dawson-Scully for their advice and for agreeing to serve on my thesis committee. I also thank provost Dr. Perry for his involvement in my project. I thank Jeanine Narayanan for editorial assistance with the publications and with this dissertation. It has been a pleasure working with various undergraduate students some of whom became lab mates including Pamela Brandao, Maria Julia Chapado and Sheilin Hamid. I thank them for their expert help in the projects we were involved in. Lastly, I want to express my profound thanks to my parents and brother for their unconditional love, support and guidance over the last couple of years. They were my rock when I was in doubt and never let me give up. I would also like to thank my boyfriend Spencer Daniel and best friends for being part of an incredible support system. -
Supporting Information
Supporting Information Friedman et al. 10.1073/pnas.0812446106 SI Results and Discussion intronic miR genes in these protein-coding genes. Because in General Phenotype of Dicer-PCKO Mice. Dicer-PCKO mice had many many cases the exact borders of the protein-coding genes are defects in additional to inner ear defects. Many of them died unknown, we searched for miR genes up to 10 kb from the around birth, and although they were born at a similar size to hosting-gene ends. Out of the 488 mouse miR genes included in their littermate heterozygote siblings, after a few weeks the miRBase release 12.0, 192 mouse miR genes were found as surviving mutants were smaller than their heterozygote siblings located inside (distance 0) or in the vicinity of the protein-coding (see Fig. 1A) and exhibited typical defects, which enabled their genes that are expressed in the P2 cochlear and vestibular SE identification even before genotyping, including typical alopecia (Table S2). Some coding genes include huge clusters of miRNAs (in particular on the nape of the neck), partially closed eyelids (e.g., Sfmbt2). Other genes listed in Table S2 as coding genes are [supporting information (SI) Fig. S1 A and C], eye defects, and actually predicted, as their transcript was detected in cells, but weakness of the rear legs that were twisted backwards (data not the predicted encoded protein has not been identified yet, and shown). However, while all of the mutant mice tested exhibited some of them may be noncoding RNAs. Only a single protein- similar deafness and stereocilia malformation in inner ear HCs, coding gene that is differentially expressed in the cochlear and other defects were variable in their severity. -
Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors
University of Cincinnati Date: 12/20/2010 I, Arturo R Maldonado , hereby submit this original work as part of the requirements for the degree of Doctor of Philosophy in Developmental Biology. It is entitled: Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors Student's name: Arturo R Maldonado This work and its defense approved by: Committee chair: Jeffrey Whitsett Committee member: Timothy Crombleholme, MD Committee member: Dan Wiginton, PhD Committee member: Rhonda Cardin, PhD Committee member: Tim Cripe 1297 Last Printed:1/11/2011 Document Of Defense Form Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors A dissertation submitted to the Graduate School of the University of Cincinnati College of Medicine in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (PH.D.) in the Division of Molecular & Developmental Biology 2010 By Arturo Rafael Maldonado B.A., University of Miami, Coral Gables, Florida June 1993 M.D., New Jersey Medical School, Newark, New Jersey June 1999 Committee Chair: Jeffrey A. Whitsett, M.D. Advisor: Timothy M. Crombleholme, M.D. Timothy P. Cripe, M.D. Ph.D. Dan Wiginton, Ph.D. Rhonda D. Cardin, Ph.D. ABSTRACT Since 1999, cancer has surpassed heart disease as the number one cause of death in the US for people under the age of 85. Malignant Peripheral Nerve Sheath Tumor (MPNST), a common malignancy in patients with Neurofibromatosis, and colorectal cancer are midkine- producing tumors with high mortality rates. In vitro and preclinical xenograft models of MPNST were utilized in this dissertation to study the role of midkine (MDK), a tumor-specific gene over- expressed in these tumors and to test the efficacy of a MDK-transcriptionally targeted oncolytic HSV-1 (oHSV). -
Receptor Signaling Through Osteoclast-Associated Monocyte
Downloaded from http://www.jimmunol.org/ by guest on September 29, 2021 is online at: average * The Journal of Immunology The Journal of Immunology , 20 of which you can access for free at: 2015; 194:3169-3179; Prepublished online 27 from submission to initial decision 4 weeks from acceptance to publication February 2015; doi: 10.4049/jimmunol.1402800 http://www.jimmunol.org/content/194/7/3169 Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor Heidi S. Schultz, Louise M. Nitze, Louise H. Zeuthen, Pernille Keller, Albrecht Gruhler, Jesper Pass, Jianhe Chen, Li Guo, Andrew J. Fleetwood, John A. Hamilton, Martin W. Berchtold and Svetlana Panina J Immunol cites 43 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Author Choice option Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Freely available online through http://www.jimmunol.org/content/suppl/2015/02/27/jimmunol.140280 0.DCSupplemental This article http://www.jimmunol.org/content/194/7/3169.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Author Choice Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. -
Genetic Amplification of the NOTCH Modulator LNX2 Upregulates The
Cancer Tumor and Stem Cell Biology Research Genetic Amplification of the NOTCH Modulator LNX2 Upregulates the WNT/b-Catenin Pathway in Colorectal Cancer Jordi Camps1, Jason J. Pitt2, Georg Emons1,3, Amanda B. Hummon1, Chanelle M. Case1, Marian Grade1,3, Tamara L. Jones2, Quang T. Nguyen1, B. Michael Ghadimi3, Tim Beissbarth3, Michael J. Difilippantonio1, Natasha J. Caplen2, and Thomas Ried1 Abstract Chromosomal copy number alterations (aneuploidy) define the genomic landscape of most cancer cells, but identification of the oncogenic drivers behind these imbalances remains an unfinished task. In this study, we conducted a systematic analysis of colorectal carcinomas that integrated genomic copy number changes and gene expression profiles. This analysis revealed 44 highly overexpressed genes mapping to localized amplicons on chromosome 13, gains of which occur often in colorectal cancers (CRC). RNA interference (RNAi)–mediated silencing identified eight candidates whose loss-of-function reduced cell viability 20% or more in CRC cell lines. The functional space of the genes NUPL1, LNX2, POLR1D, POMP, SLC7A1, DIS3, KLF5, and GPR180 was established by global expression profiling after RNAi exposure. One candidate, LNX2, not previously known as an oncogene, was involved in regulating NOTCH signaling. Silencing LNX2 reduced NOTCH levels but also downregulated the transcription factor TCF7L2 and markedly reduced WNT signaling. LNX2 overexpression and chromosome 13 amplification therefore constitutively activates the WNT pathway, offering evidence of an aberrant NOTCH–WNT axis in CRC. Cancer Res; 73(6); 1–11. Ó2012 AACR. Introduction band or less) or they affect entire chromosome arms or Colorectal cancer (CRC) has an annual incidence of some chromosomes, most commonly resulting in low level gains or 150,000 new cases and a mortality of more than 50,000 in the losses. -
Identifying Blood Biomarkers for Mood Disorders Using Convergent
Molecular Psychiatry (2009) 14, 156–174 & 2009 Nature Publishing Group All rights reserved 1359-4184/09 $32.00 www.nature.com/mp ORIGINAL ARTICLE Identifying blood biomarkers for mood disorders using convergent functional genomics H Le-Niculescu1,2,3, SM Kurian4, N Yehyawi1,5, C Dike1,5, SD Patel1,3, HJ Edenberg6, MT Tsuang7, DR Salomon4, JI Nurnberger Jr3 and AB Niculescu1,2,3,5 1Laboratory of Neurophenomics, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; 2INBRAIN, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; 3Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; 4Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA; 5Indianapolis VA Medical Center, Indianapolis, IN, USA; 6Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA and 7Department of Psychiatry, University of California at San Diego, La Jolla, CA, USA There are to date no objective clinical laboratory blood tests for mood disorders. The current reliance on patient self-report of symptom severity and on the clinicians’ impression is a rate- limiting step in effective treatment and new drug development. We propose, and provide proof of principle for, an approach to help identify blood biomarkers for mood state. We measured whole-genome gene expression differences in blood samples from subjects with bipolar disorder that had low mood vs those that had high mood at the time of the blood draw, and separately, changes in gene expression in brain and blood of a mouse pharmacogenomic model. We then integrated our human blood gene expression data with animal model gene expression data, human genetic linkage/association data and human postmortem brain data, an approach called convergent functional genomics, as a Bayesian strategy for cross- validating and prioritizing findings. -
High-Density Array Comparative Genomic Hybridization Detects Novel Copy Number Alterations in Gastric Adenocarcinoma
ANTICANCER RESEARCH 34: 6405-6416 (2014) High-density Array Comparative Genomic Hybridization Detects Novel Copy Number Alterations in Gastric Adenocarcinoma ALINE DAMASCENO SEABRA1,2*, TAÍSSA MAÍRA THOMAZ ARAÚJO1,2*, FERNANDO AUGUSTO RODRIGUES MELLO JUNIOR1,2, DIEGO DI FELIPE ÁVILA ALCÂNTARA1,2, AMANDA PAIVA DE BARROS1,2, PAULO PIMENTEL DE ASSUMPÇÃO2, RAQUEL CARVALHO MONTENEGRO1,2, ADRIANA COSTA GUIMARÃES1,2, SAMIA DEMACHKI2, ROMMEL MARIO RODRÍGUEZ BURBANO1,2 and ANDRÉ SALIM KHAYAT1,2 1Human Cytogenetics Laboratory and 2Oncology Research Center, Federal University of Pará, Belém Pará, Brazil Abstract. Aim: To investigate frequent quantitative alterations gastric cancer is the second most frequent cancer in men and of intestinal-type gastric adenocarcinoma. Materials and the third in women (4). The state of Pará has a high Methods: We analyzed genome-wide DNA copy numbers of 22 incidence of gastric adenocarcinoma and this disease is a samples and using CytoScan® HD Array. Results: We identified public health problem, since mortality rates are above the 22 gene alterations that to the best of our knowledge have not Brazilian average (5). been described for gastric cancer, including of v-erb-b2 avian This tumor can be classified into two histological types, erythroblastic leukemia viral oncogene homolog 4 (ERBB4), intestinal and diffuse, according to Laurén (4, 6, 7). The SRY (sex determining region Y)-box 6 (SOX6), regulator of intestinal type predominates in high-risk areas, such as telomere elongation helicase 1 (RTEL1) and UDP- Brazil, and arises from precursor lesions, whereas the diffuse Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 5 type has a similar distribution in high- and low-risk areas and (B4GALT5). -
HHS Public Access Provided by Iupuischolarworks Author Manuscript
View metadata, citation and similar papers at core.ac.uk brought to you by CORE HHS Public Access provided by IUPUIScholarWorks Author manuscript Author Manuscript Author ManuscriptPharmacol Author Manuscript Biochem Behav Author Manuscript . Author manuscript; available in PMC 2015 July 27. Published in final edited form as: Pharmacol Biochem Behav. 2008 June ; 89(4): 481–498. doi:10.1016/j.pbb.2008.01.023. Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats Zachary A. Rodd1,6, Mark W. Kimpel1,6, Howard J. Edenberg2,4,5, Richard L. Bell1,6, Wendy N. Strother1,6, Jeanette N. McClintick2,5, Lucinda G. Carr3, Tiebing Liang3, and William J. McBride1,6 1Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202-4887 2Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202-4887 3Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-4887 4Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202-4887 5Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202-4887 6Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202-4887 Abstract The current study examined the effects of operant ethanol (EtOH) self-administration on gene expression in the nucleus accumbens (ACB) and amygdala (AMYG) of inbred alcohol-preferring (iP) rats. Rats self-trained on a standard two-lever operant paradigm to administer either water- water, EtOH (15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were killed 24 hr after the last operant session, and the ACB and AMYG dissected; RNA was extracted and purified for microarray analysis.