WO 2012/135397 A2 4 October 2012 (04.10.2012) P O P C T
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HPSE2 Gene Heparanase 2 (Inactive)
HPSE2 gene heparanase 2 (inactive) Normal Function The HPSE2 gene provides instructions for making a protein called heparanase 2. Little is known about this protein, but its structure is similar to that of another protein called heparanase 1. Heparanase 1 is an enzyme that splits (cleaves) molecules called heparan sulfate proteoglycans (HSPGs) by removing the heparan sulfate portion (the side chain). HSPGs are important parts of the lattice of proteins and other molecules outside the cell (extracellular matrix) and of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Cleavage of HSPGs by heparanase 1 may lead to changes in the basement membrane or extracellular matrix that allow cell movement or release of substances from the cell. The specific function of the heparanase 2 enzyme is not well understood, but studies suggest that it may block the action of heparanase 1. Health Conditions Related to Genetic Changes Migraine MedlinePlus Genetics provides information about Migraine Ochoa syndrome At least nine HPSE2 gene mutations have been identified in people with Ochoa syndrome (also called urofacial syndrome), a disorder that causes urinary problems and unusual facial expressions. These mutations result in changes in the heparanase 2 protein that likely prevent it from functioning. The connection between HPSE2 gene mutations and the features of Ochoa syndrome are unclear. Because the areas of the brain that control facial expression and urination are in close proximity, some researchers have suggested that the genetic changes may lead to an abnormality in this brain region that may account for the symptoms of Ochoa syndrome. -
The Title of the Article
Mechanism-Anchored Profiling Derived from Epigenetic Networks Predicts Outcome in Acute Lymphoblastic Leukemia Xinan Yang, PhD1, Yong Huang, MD1, James L Chen, MD1, Jianming Xie, MSc2, Xiao Sun, PhD2, Yves A Lussier, MD1,3,4§ 1Center for Biomedical Informatics and Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637 USA 2State Key Laboratory of Bioelectronics, Southeast University, 210096 Nanjing, P.R.China 3The University of Chicago Cancer Research Center, and The Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637 USA 4The Institute for Genomics and Systems Biology, and the Computational Institute, The University of Chicago, Chicago, IL 60637 USA §Corresponding author Email addresses: XY: [email protected] YH: [email protected] JC: [email protected] JX: [email protected] XS: [email protected] YL: [email protected] - 1 - Abstract Background Current outcome predictors based on “molecular profiling” rely on gene lists selected without consideration for their molecular mechanisms. This study was designed to demonstrate that we could learn about genes related to a specific mechanism and further use this knowledge to predict outcome in patients – a paradigm shift towards accurate “mechanism-anchored profiling”. We propose a novel algorithm, PGnet, which predicts a tripartite mechanism-anchored network associated to epigenetic regulation consisting of phenotypes, genes and mechanisms. Genes termed as GEMs in this network meet all of the following criteria: (i) they are co-expressed with genes known to be involved in the biological mechanism of interest, (ii) they are also differentially expressed between distinct phenotypes relevant to the study, and (iii) as a biomodule, genes correlate with both the mechanism and the phenotype. -
Urinary Tract Effects of HPSE2 Mutations
BRIEF COMMUNICATION www.jasn.org Urinary Tract Effects of HPSE2 Mutations † Helen M. Stuart,* Neil A. Roberts,* Emma N. Hilton,* Edward A. McKenzie, Sarah B. Daly,* † ‡ Kristen D. Hadfield,* Jeffery S. Rahal,* Natalie J. Gardiner, Simon W. Tanley, | Malcolm A. Lewis,* Emily Sites,§ Brad Angle,§ Cláudia Alves, Teresa Lourenço,¶ Márcia Rodrigues,¶ Angelina Calado,** Marta Amado,** Nancy Guerreiro,** Inês Serras,** †† †† || Christian Beetz , Rita-Eva Varga , Mesrur Selcuk Silay,§§ John M. Darlow, ¶¶ || || ††† Mark G. Dobson , ¶¶ David E. Barton , *** Manuela Hunziker,¶¶ Prem Puri,¶¶*** ‡‡‡ Sally A. Feather, Judith A. Goodship ,§§§ Timothy H.J. Goodship ,§§§ Heather J. ||| BRIEF COMMUNICATION Lambert ,§§§ Heather J. Cordell ,§§§ the UK VUR Study Group, Anand Saggar, †††† Maria Kinali ,¶¶¶, the 4C Study Group, Christian Lorenz ,**** Kristina Moeller, |||| Franz Schaefer,§§§§ Aysun K. Bayazit , Stefanie Weber,¶¶¶¶ William G. Newman ,* and Adrian S. Woolf * Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing grimacing and dysmorphic bladders. and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a Considering these and previously pub- heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spec- lished mutations4–7 (Figure 1A), it is clear trum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, that pathogenic HPSE2 mutations are including one with deleted asparagine 254, suggesting a role for this amino acid, found across the gene’s coding region. which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non- Most (i.e., nonsense or frameshift muta- neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic tions) would cause loss of function, but a vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. -
Mouse Germ Line Mutations Due to Retrotransposon Insertions Liane Gagnier1, Victoria P
Gagnier et al. Mobile DNA (2019) 10:15 https://doi.org/10.1186/s13100-019-0157-4 REVIEW Open Access Mouse germ line mutations due to retrotransposon insertions Liane Gagnier1, Victoria P. Belancio2 and Dixie L. Mager1* Abstract Transposable element (TE) insertions are responsible for a significant fraction of spontaneous germ line mutations reported in inbred mouse strains. This major contribution of TEs to the mutational landscape in mouse contrasts with the situation in human, where their relative contribution as germ line insertional mutagens is much lower. In this focussed review, we provide comprehensive lists of TE-induced mouse mutations, discuss the different TE types involved in these insertional mutations and elaborate on particularly interesting cases. We also discuss differences and similarities between the mutational role of TEs in mice and humans. Keywords: Endogenous retroviruses, Long terminal repeats, Long interspersed elements, Short interspersed elements, Germ line mutation, Inbred mice, Insertional mutagenesis, Transcriptional interference Background promoter and polyadenylation motifs and often a splice The mouse and human genomes harbor similar types of donor site [10, 11]. Sequences of full-length ERVs can TEs that have been discussed in many reviews, to which encode gag, pol and sometimes env, although groups of we refer the reader for more in depth and general infor- LTR retrotransposons with little or no retroviral hom- mation [1–9]. In general, both human and mouse con- ology also exist [6–9]. While not the subject of this re- tain ancient families of DNA transposons, none view, ERV LTRs can often act as cellular enhancers or currently active, which comprise 1–3% of these genomes promoters, creating chimeric transcripts with genes, and as well as many families or groups of retrotransposons, have been implicated in other regulatory functions [11– which have caused all the TE insertional mutations in 13]. -
Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2010 Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis Ryan Fassnacht Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Physiology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2246 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Ryan C. Fassnacht 2010 All Rights Reserved Molecular Mechanisms Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. by Ryan Christopher Fassnacht, B.S. Hampden Sydney University, 2005 M.S. Virginia Commonwealth University, 2010 Director: Valeria Mas, Ph.D., Associate Professor of Surgery and Pathology Division of Transplant Department of Surgery Virginia Commonwealth University Richmond, Virginia July 9, 2010 Acknowledgement The Author wishes to thank his family and close friends for their support. He would also like to thank the members of the molecular transplant team for their help and advice. This project would not have been possible with out the help of Dr. Valeria Mas and her endearing -
Mathiomica: an Integrative Platform for Dynamic Omics George I
MathIOmica: An Integrative Platform for Dynamic Omics George I. Mias1,*, Tahir Yusufaly2, Raeuf Roushangar1, Lavida R. K. Brooks1, Vikas V. Singh1, and Christina Christou3 1Michigan State University, Biochemistry and Molecular Biology, East Lansing, MI 48824, USA 2University of Southern California, Department of Physics and Astronomy, Los Angeles, CA, 90089, USA 3Mercy Cancer Center, Department of Radiation Oncology, Mason City, IA 50401, USA *[email protected] SUPPLEMENTARY NOTE 1 1 1 MathIOmica: Omics Analysis Tutorial Loading the MathIOmica Package Metabolomic Data Data in MathIOmica Combined Data Clustering Transcriptome Data Visualization Proteomic Data Annotation and Enrichment MathIOmica is an omics analysis package designed to facilitate method development for the analysis of multiple omics in Mathematica, particularly for dynamics (time series/longitudinal data). This extensive tutorial follows the analysis of multiple dynamic omics data (transcriptomics, proteomics, and metabolomics from human samples). Various MathIOmica functions are introduced in the tutorial, including additional discussion of related functionality. We should note that the approach methods are simply an illustration of MathIOmica functionality, and should not be considered as a definitive appoach. Additionally, certain details are included to illustrate common complications (e.g. renaming samples, combining datasets, transforming accessions from one database to another, dealing with replicates and Missing data, etc.). After a brief discussion of data in MathIOmica, each example data (transcriptome, proteome and metabolome) are imported and preprocessed. Next a simulation is carried out to obtain datasets for each omics used to assess statistical significance cutoffs. The datasets are combined, and classified for time series patterns, followed by clustering. The clusters are visualized, and biological annotation of Gene Ontology (GO) and pathway analysis (KEGG: Kyoto Encyclopedia of Genes and Genomes) are finally considered. -
Supplementary Information Integrative Analyses of Splicing in the Aging Brain: Role in Susceptibility to Alzheimer’S Disease
Supplementary Information Integrative analyses of splicing in the aging brain: role in susceptibility to Alzheimer’s Disease Contents 1. Supplementary Notes 1.1. Religious Orders Study and Memory and Aging Project 1.2. Mount Sinai Brain Bank Alzheimer’s Disease 1.3. CommonMind Consortium 1.4. Data Availability 2. Supplementary Tables 3. Supplementary Figures Note: Supplementary Tables are provided as separate Excel files. 1. Supplementary Notes 1.1. Religious Orders Study and Memory and Aging Project Gene expression data1. Gene expression data were generated using RNA- sequencing from Dorsolateral Prefrontal Cortex (DLPFC) of 540 individuals, at an average sequence depth of 90M reads. Detailed description of data generation and processing was previously described2 (Mostafavi, Gaiteri et al., under review). Samples were submitted to the Broad Institute’s Genomics Platform for transcriptome analysis following the dUTP protocol with Poly(A) selection developed by Levin and colleagues3. All samples were chosen to pass two initial quality filters: RNA integrity (RIN) score >5 and quantity threshold of 5 ug (and were selected from a larger set of 724 samples). Sequencing was performed on the Illumina HiSeq with 101bp paired-end reads and achieved coverage of 150M reads of the first 12 samples. These 12 samples will serve as a deep coverage reference and included 2 males and 2 females of nonimpaired, mild cognitive impaired, and Alzheimer's cases. The remaining samples were sequenced with target coverage of 50M reads; the mean coverage for the samples passing QC is 95 million reads (median 90 million reads). The libraries were constructed and pooled according to the RIN scores such that similar RIN scores would be pooled together. -
Viewed the Thesis/Dissertation in Its Final Electronic Format and Certify That It Is an Accurate Copy of the Document Reviewed and Approved by the Committee
U UNIVERSITY OF CINCINNATI Date: I, , hereby submit this original work as part of the requirements for the degree of: in It is entitled: Student Signature: This work and its defense approved by: Committee Chair: Approval of the electronic document: I have reviewed the Thesis/Dissertation in its final electronic format and certify that it is an accurate copy of the document reviewed and approved by the committee. Committee Chair signature: Investigation of Phosphorylated Proteins and Peptides in Human Cerebrospinal Fluid via High-Performance Liquid Chromatography Coupled to Elemental and Molecular Mass Spectrometry A thesis submitted to the Graduate School of the University of Cincinnati In partial fulfillment of the Requirements for the degree of MASTER OF SCIENCE In the Department of Chemistry of the College of Arts and Sciences By ORVILLE DEAN STUART B.S., Chemistry The University of Texas at Tyler, Tyler, Texas May 2006 Committee Chair: Joseph A. Caruso, Ph.D Abstract Cerebrospinal fluid (CSF) surrounds and serves as a protective media for the brain and central nervous system (CNS). This fluid remains isolated from other biological matrices in normal bodily conditions, therefore, an in depth analysis of CSF has the potential to reveal important details and malfunctions of many diseases that plague the nervous system. Because phosphorylation of a wide variety of proteins governs the activity of biological enzymes and systems, a method for the detection of 31P in proteins found in human cerebrospinal fluid by high-performance liquid chromatography (HPLC) coupled to inductively coupled plasma mass spectrometry (ICPMS) is described. Specifically, it is of interest to compare phosphorylated proteins/peptides from patients suffering from post subarachnoid hemorrhage (SAH) arterial vasospasms against CSF from non-diseased patients. -
Identification and Characterization of TPRKB Dependency in TP53 Deficient Cancers
Identification and Characterization of TPRKB Dependency in TP53 Deficient Cancers. by Kelly Kennaley A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Molecular and Cellular Pathology) in the University of Michigan 2019 Doctoral Committee: Associate Professor Zaneta Nikolovska-Coleska, Co-Chair Adjunct Associate Professor Scott A. Tomlins, Co-Chair Associate Professor Eric R. Fearon Associate Professor Alexey I. Nesvizhskii Kelly R. Kennaley [email protected] ORCID iD: 0000-0003-2439-9020 © Kelly R. Kennaley 2019 Acknowledgements I have immeasurable gratitude for the unwavering support and guidance I received throughout my dissertation. First and foremost, I would like to thank my thesis advisor and mentor Dr. Scott Tomlins for entrusting me with a challenging, interesting, and impactful project. He taught me how to drive a project forward through set-backs, ask the important questions, and always consider the impact of my work. I’m truly appreciative for his commitment to ensuring that I would get the most from my graduate education. I am also grateful to the many members of the Tomlins lab that made it the supportive, collaborative, and educational environment that it was. I would like to give special thanks to those I’ve worked closely with on this project, particularly Dr. Moloy Goswami for his mentorship, Lei Lucy Wang, Dr. Sumin Han, and undergraduate students Bhavneet Singh, Travis Weiss, and Myles Barlow. I am also grateful for the support of my thesis committee, Dr. Eric Fearon, Dr. Alexey Nesvizhskii, and my co-mentor Dr. Zaneta Nikolovska-Coleska, who have offered guidance and critical evaluation since project inception. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Analysis of BMP4 and BMP7 Signaling in Breast Cancer Cells Unveils Time
Rodriguez-Martinez et al. BMC Medical Genomics 2011, 4:80 http://www.biomedcentral.com/1755-8794/4/80 RESEARCHARTICLE Open Access Analysis of BMP4 and BMP7 signaling in breast cancer cells unveils time-dependent transcription patterns and highlights a common synexpression group of genes Alejandra Rodriguez-Martinez1†, Emma-Leena Alarmo1†, Lilli Saarinen2, Johanna Ketolainen1, Kari Nousiainen2, Sampsa Hautaniemi2 and Anne Kallioniemi1* Abstract Background: Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of growth factors. They are known for their roles in regulation of osteogenesis and developmental processes and, in recent years, evidence has accumulated of their crucial functions in tumor biology. BMP4 and BMP7, in particular, have been implicated in breast cancer. However, little is known about BMP target genes in the context of tumor. We explored the effects of BMP4 and BMP7 treatment on global gene transcription in seven breast cancer cell lines during a 6- point time series, using a whole-genome oligo microarray. Data analysis included hierarchical clustering of differentially expressed genes, gene ontology enrichment analyses and model based clustering of temporal data. Results: Both ligands had a strong effect on gene expression, although the response to BMP4 treatment was more pronounced. The cellular functions most strongly affected by BMP signaling were regulation of transcription and development. The observed transcriptional response, as well as its functional outcome, followed a temporal sequence, with regulation of gene expression and signal transduction leading to changes in metabolism and cell proliferation. Hierarchical clustering revealed distinct differences in the response of individual cell lines to BMPs, but also highlighted a synexpression group of genes for both ligands. -
The Porcine Major Histocompatibility Complex and Related Paralogous Regions: a Review Patrick Chardon, Christine Renard, Claire Gaillard, Marcel Vaiman
The porcine Major Histocompatibility Complex and related paralogous regions: a review Patrick Chardon, Christine Renard, Claire Gaillard, Marcel Vaiman To cite this version: Patrick Chardon, Christine Renard, Claire Gaillard, Marcel Vaiman. The porcine Major Histocom- patibility Complex and related paralogous regions: a review. Genetics Selection Evolution, BioMed Central, 2000, 32 (2), pp.109-128. 10.1051/gse:2000101. hal-00894302 HAL Id: hal-00894302 https://hal.archives-ouvertes.fr/hal-00894302 Submitted on 1 Jan 2000 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. Genet. Sel. Evol. 32 (2000) 109–128 109 c INRA, EDP Sciences Review The porcine Major Histocompatibility Complex and related paralogous regions: a review Patrick CHARDON, Christine RENARD, Claire ROGEL GAILLARD, Marcel VAIMAN Laboratoire de radiobiologie et d’etude du genome, Departement de genetique animale, Institut national de la recherche agronomique, Commissariat al’energie atomique, 78352, Jouy-en-Josas Cedex, France (Received 18 November 1999; accepted 17 January 2000) Abstract – The physical alignment of the entire region of the pig major histocompat- ibility complex (MHC) has been almost completed. In swine, the MHC is called the SLA (swine leukocyte antigen) and most of its class I region has been sequenced.