Rab18 Promotes Lipid Droplet (LD) Growth by Tethering the ER to Lds Through SNARE and NRZ Interactions
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Gene Expression Imputation Across Multiple Brain Regions Provides Insights Into Schizophrenia Risk
VU Research Portal Gene expression imputation across multiple brain regions provides insights into schizophrenia risk iPSYCH-GEMS Schizophrenia Working Group; CommonMind Consortium; The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium published in Nature Genetics 2019 DOI (link to publisher) 10.1038/s41588-019-0364-4 document version Publisher's PDF, also known as Version of record document license Article 25fa Dutch Copyright Act Link to publication in VU Research Portal citation for published version (APA) iPSYCH-GEMS Schizophrenia Working Group, CommonMind Consortium, & The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium (2019). Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51(4), 659–674. https://doi.org/10.1038/s41588-019-0364-4 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 28. -
Loss-Of-Function Mutations in RAB18 Cause Warburg Micro Syndrome
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REPORT Loss-of-Function Mutations in RAB18 Cause Warburg Micro Syndrome Danai Bem,1 Shin-Ichiro Yoshimura,2,12 Ricardo Nunes-Bastos,2 Frances F. Bond,3 Manju A. Kurian,1,13 Fatima Rahman,1 Mark T.W. Handley,4 Yavor Hadzhiev,1 Imran Masood,5 Ania A. Straatman-Iwanowska,1,13 Andrew R. Cullinane,1,14 Alisdair McNeill,1,3,15 Shanaz S. Pasha,1 Gail A. Kirby,1 Katharine Foster,6 Zubair Ahmed,7 Jenny E. Morton,3 Denise Williams,3 John M. Graham,8 William B. Dobyns,9 Lydie Burglen,10 John R. Ainsworth,11 Paul Gissen,1,13 Ferenc Mu¨ller,1 Eamonn R. Maher,1,3 Francis A. Barr,2 and Irene A. Aligianis1,3,16,* Warburg Micro syndrome and Martsolf syndrome are heterogenous autosomal-recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Previously, identification of mutations in RAB3GAP1 and RAB3GAP2 in both these syndromes implicated dysregulation of the RAB3 cycle (which controls calcium-mediated exocytosis of neurotransmitters and hormones) in disease pathogenesis. RAB3GAP1 and RAB3GAP2 encode the catalytic and noncatalytic subunits of the hetrodimeric enzyme RAB3GAP (RAB3GTPase-activating protein), a key regulator of the RAB3 cycle. We performed autozygosity mapping in five consanguineous families without RAB3GAP1/2 mutations and identified loss-of-function mutations in RAB18. A c.71T > A (p.Leu24Gln) founder mutation was identified in four Pakistani families, and a homozygous exon 2 deletion (predicted to result in a frameshift) was found in the fifth family. -
The A–Z of Zika Drug Discovery, Drug Discov Today (2018)
Drug Discovery Today Volume 00, Number 00 June 2018 REVIEWS Teaser Zika clinical outcomes might be nefarious impacting newborns for a lifetime. There is still no drug available to cure Zika. We provide guidance to help understand and advance the search for a cure. KEYNOTE REVIEW – The A Z of Zika drug discovery Reviews 1 1 1 Melina Mottin graduated Melina Mottin , Joyce V.V.B. Borba , Rodolpho C. Braga , in pharmacy and earned her 2,3 4 Master’s degree and PhD at Pedro H.M. Torres , Matheus C. Martini , University of Campinas 4 5 (UNICAMP), Brazil. The Jose Luiz Proenca-Modena , Carla C. Judice , main focus of her studies 5 6 7 was to apply molecular Fabio T.M. Costa , Sean Ekins , Alexander L. Perryman and dynamics simulations and 1,5 other computational Carolina Horta Andrade strategies for a nuclear receptor and its association with drugs and coregulatory proteins, implicated in diabetes. 1 LabMol – Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmacia, Universidade Federal de Melina is currently Research Associate of the OpenZika project, at Federal University of Goias, mainly applying Goias – UFG, Goiânia, GO 74605-170, Brazil 2 virtual screening based on docking and QSAR models to Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21040-900, Brazil 3 select drug candidates against Zika virus. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK 4 Alexander L. Perryman Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, earned his PhD in Andy Institute of Biology, UNICAMP, Campinas, SP 13083-864, Brazil 5 McCammon’s lab at UCSD. -
Convergent Functional Genomics of Schizophrenia: from Comprehensive Understanding to Genetic Risk Prediction
Molecular Psychiatry (2012) 17, 887 -- 905 & 2012 Macmillan Publishers Limited All rights reserved 1359-4184/12 www.nature.com/mp IMMEDIATE COMMUNICATION Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction M Ayalew1,2,9, H Le-Niculescu1,9, DF Levey1, N Jain1, B Changala1, SD Patel1, E Winiger1, A Breier1, A Shekhar1, R Amdur3, D Koller4, JI Nurnberger1, A Corvin5, M Geyer6, MT Tsuang6, D Salomon7, NJ Schork7, AH Fanous3, MC O’Donovan8 and AB Niculescu1,2 We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein-- coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. -
Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights Froma Highly Derived Visual Phenotype Rui Borges Universidade Do Porto - Portugal
Nova Southeastern University NSUWorks Biology Faculty Articles Department of Biological Sciences 8-22-2019 Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights froma Highly Derived Visual Phenotype Rui Borges Universidade do Porto - Portugal Joao Fonseca Universidade do Porto - Portugal Cidalia Gomes Universidade do Porto - Portugal Warren E. Johnson Smithsonian Institution Stephen James O'Brien St. Petersburg State University - Russia; Nova Southeastern University, [email protected] See next page for additional authors Follow this and additional works at: https://nsuworks.nova.edu/cnso_bio_facarticles Part of the Biology Commons NSUWorks Citation Borges, Rui; Joao Fonseca; Cidalia Gomes; Warren E. Johnson; Stephen James O'Brien; Guojie Zhang; M. Thomas P. Gilbert; Erich D. Jarvis; and Agostinho Antunes. 2019. "Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights froma Highly Derived Visual Phenotype." Genome Biology and Evolution 11, (8): 2244-2255. doi:10.1093/gbe/evz111. This Article is brought to you for free and open access by the Department of Biological Sciences at NSUWorks. It has been accepted for inclusion in Biology Faculty Articles by an authorized administrator of NSUWorks. For more information, please contact [email protected]. Authors Rui Borges, Joao Fonseca, Cidalia Gomes, Warren E. Johnson, Stephen James O'Brien, Guojie Zhang, M. Thomas P. Gilbert, Erich D. Jarvis, and Agostinho Antunes This article is available at NSUWorks: https://nsuworks.nova.edu/cnso_bio_facarticles/982 GBE Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights from a Highly Derived Visual Downloaded from https://academic.oup.com/gbe/article-abstract/11/8/2244/5544263 by Nova Southeastern University/HPD Library user on 16 September 2019 Phenotype Rui Borges1,2,Joao~ Fonseca1,Cidalia Gomes1, Warren E. -
Identification of Rab18 As an Essential Host Factor for Bkpyv Infection Using a Whole Genome RNA 2 Interference Screen
bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 2017. 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. 1 Identification of Rab18 as an Essential Host Factor for BKPyV Infection Using a Whole Genome RNA 2 Interference Screen 3 4 Linbo Zhaoa, Michael J. Imperialea,b,* 5 6 aDepartment of Microbiology and Immunology, bComprehensive Cancer Center, University of Michigan, 7 Ann Arbor, MI, 48109, USA 8 9 10 11 12 13 14 15 16 17 18 * Corresponding author. Department of Microbiology and Immunology, 1150 West Medical Center 19 Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA. Tel. +1 (734) 763 9162. Fax: +1 (734) 20 764 3562. 21 E-mail addresses: [email protected] (L. Zhao); [email protected] (M.J. Imperiale). 22 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 2017. 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. 25 Abstract 26 27 BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the 28 human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is 29 usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes 30 two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. -
Rare Mutations in RINT1 Predispose Carriers to Breast and Lynch Syndrome–Spectrum Cancers
Published OnlineFirst May 2, 2014; DOI: 10.1158/2159-8290.CD-14-0212 RESEARCH ARTICLE Rare Mutations in RINT1 Predispose Carriers to Breast and Lynch Syndrome–Spectrum Cancers Daniel J. Park 1 , K a y o k o Ta o 7 , Florence Le Calvez-Kelm 17 , Tu Nguyen-Dumont 1 , Nivonirina Robinot 17 , Fleur Hammet1 , Fabrice Odefrey 1 , Helen Tsimiklis 1 , Zhi L. Teo 1 , Louise B. Thingholm 1 , Erin L. Young 7 , Catherine Voegele 17 , Andrew Lonie 4 , Bernard J. Pope 2 , 4 , Terrell C. Roane 10 , Russell Bell 7 , Hao Hu 11 , Shankaracharya 11 , Chad D. Huff 11 , Jonathan Ellis 6 , Jun Li 6 , Igor V. Makunin 6 , Esther M. John 12 , 13 , Irene L. Andrulis 19 , Mary B. Terry 14 , Mary Daly 15 , Saundra S. Buys 9 , Carrie Snyder 16 , Henry T. Lynch 16 , Peter Devilee20 , Graham G. Giles 3 , 5 , John L. Hopper 3 , 21 , Bing-Jian Feng 8 , 9 , Fabienne Lesueur 17 , 18 , Sean V. Tavtigian 7 , Melissa C. Southey 1 , and David E. Goldgar 8 , 9 ABSTRACT Approximately half of the familial aggregation of breast cancer remains unex- plained. A multiple-case breast cancer family exome-sequencing study identifi ed three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing data- bases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this fi nding, a population-based case–control mutation-screening study was conducted that identifi ed 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi - dence interval (CI), 1.29–8.17; P = 0.013]. -
Large Homozygous RAB3GAP1 Gene Microdeletion Causes Warburg
Picker-Minh et al. Orphanet Journal of Rare Diseases 2014, 9:113 http://www.ojrd.com/content/9/1/113 LETTER TO THE EDITOR Open Access Large homozygous RAB3GAP1 gene microdeletion causes Warburg Micro Syndrome 1 Sylvie Picker-Minh1,2,3, Andreas Busche4, Britta Hartmann4, Birgit Spors5, Eva Klopocki6,7, Christoph Hübner1, Denise Horn6 and Angela M Kaindl1,2,3* Abstract Warburg micro syndrome (WARBM) is a genetic heterogeneous disease characterized by microcephaly, intellectual disability, brain, ocular, and endocrine anomalies. WARBM1-4 can be caused by biallelic mutations of the RAB3GAP1 (RAB3 GTPase-activating protein 1), RAB3GAP2, RAB18 (RAS-associated protein RAB18), or TBC1D20 (TBC1 domain protein, member 20) gene, respectively. Here, we delineate the so far largest intragenic homozygous RAB3GAP1 microdeletion. Despite the size of the RAB3GAP1 gene deletion, the patient phenotype is mainly consistent with that of other WARBM1 patients, supporting strongly the theory that WARBM1 is caused by a loss of RAB3GAP1 function. We further highlight osteopenia as a feature of WARBM1. Keywords: RAB3GAP1, WARBM, Warburg micro syndrome, Microcephaly, Intellectual disability, Congenital cataract, Array CGH Letter to the editor protein-function [1,2,4-7], putatively explaining the lack of Warburg micro syndrome (WARBM) is a rare autosomal a genotype-phenotype correlation. We here report the lar- recessive disorder characterized by neurodevelopmental gest RAB3GAP1 gene microdeletion to date in patients abnormalities such as congenital or postnatal microcephaly, with WARBM1 and compare their phenotype with that of severe intellectual disability, pachy- or polymicrogyria, other WARBM1 patients. The two index patients were and hypoplasia/agenesis of the corpus callosum as well as born at term without complications as the first and second ocular manifestations including congenital cataract, micro- child of healthy, consanguineous parents of Kurdish- cornea, microphthalmia, and optic atrophy [1-3]. -
On the Role of Chromosomal Rearrangements in Evolution
On the role of chromosomal rearrangements in evolution: Reconstruction of genome reshuffling in rodents and analysis of Robertsonian fusions in a house mouse chromosomal polymorphism zone by Laia Capilla Pérez A thesis submitted for the degree of Doctor of Philosophy in Animal Biology Supervisors: Dra. Aurora Ruiz-Herrera Moreno and Dr. Jacint Ventura Queija Institut de Biotecnologia i Biomedicina (IBB) Departament de Biologia Cel·lular, Fisiologia i Immunologia Departament de Biologia Animal, Biologia Vegetal i Ecologia Universitat Autònoma de Barcelona Supervisor Supervisor PhD candidate Aurora Ruiz-Herrera Moreno Jacint Ventura Queija Laia Capilla Pérez Bellaterra, 2015 A la mare Al pare Al mano “Visto a la luz de la evolución, la biología es, quizás, la ciencia más satisfactoria e inspiradora. Sin esa luz, se convierte en un montón de hechos varios, algunos de ellos interesantes o curiosos, pero sin formar ninguna visión conjunta.” Theodosius Dobzhansky “La evolución es tan creativa. Por eso tenemos jirafas.” Kurt Vonnegut This thesis was supported by grants from: • Ministerio de Economía y Competitividad (CGL2010-15243 and CGL2010- 20170). • Generalitat de Catalunya, GRQ 1057. • Ministerio de Economía y Competitividad. Beca de Formación de Personal Investigador (FPI) (BES-2011-047722). • Ministerio de Economía y Competitividad. Beca para la realización de estancias breves (EEBB-2011-07350). Covers designed by cintamontserrat.blogspot.com INDEX Abstract 15-17 Acronyms 19-20 1. GENERAL INTRODUCTION 21-60 1.1 Chromosomal rearrangements -
D82b54407ece9642da45e12eee
Oxford Medical Case Reports, 2020;4,1–3 doi: 10.1093/omcr/omaa031 Case Report CASE REPORT Novel mutation in the RAB3GAP1 gene, the first diagnosed Warburg Micro syndrome case in Syria Soubhi Tenawi1,†, Rawan Al Khudari1,†,* and Diana Alasmar2 1Faculty of Medicine, Damascus University, Damascus, Syria, 2Professor of Inborn Errors of Metabolism, Pediatrics Department, Damascus University, Damascus, Syria *Correspondence address. Faculty of Medicine, Damascus University, Damascus, Syria. Tel: +963992336336; E-mail: [email protected] Abstract Warburg Micro syndrome is a rare autosomal recessive disease due to mutation in the RAB3GAP1, RAB3GAP2, RAB18 and TBC1D20 genes. It is commonly seen in consanguineous marriages, characterized by optic (microcornea, microphthalmia, congenital cataracts), neurologic )microcephaly, corpus callosum hypoplasia, severe mental retardation( and hypogonadism; some non-typical findings could be present (cardiomyopathy, peripheral neuropathy). We report a novel homozygous mutation in the RAB3GAP1 gene in a 7-month-old boy from healthy nonconsanguineous parents from the same village in Syria, with bilateral congenital cataracts, hypogonadism, muscular hypotonia and severe developmental delay. Whole exome sequencing (WES) showed a homozygous mutation in the c.2195del p.(Pro732Glnfs∗6) in exon 19 of the RAB3GAP1 gene, which is likely pathogenic and correlates with Warburg Micro syndrome type 1. INTRODUCTION eye and brain [4]. Here, we report a novel RAB3GAP1 homozygous mutation in a child with WARBM. Warburg Micro syndrome (WARBM) is a rare autosomal reces- sive disorder characterized by postnatal growth retardation, hypoplasia of the corpus callosum, microcephalus, delayed CASE REPORT motor development, severe intellectual disability, microph- thalmia, microcornea, congenital cataracts, optic atrophy and A 7-month-old boy presented to Children’s University Hospi- hypogonadism [1]. -
Evaluation of Rint1 As a Modifier of Intestinal Tumorigenesis and Cancer Risk
RESEARCH ARTICLE Evaluation of Rint1 as a modifier of intestinal tumorigenesis and cancer risk Karla L. Otterpohl¤, Karen A. Gould* Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America ¤ Current address: Children's Health Research Center, Sanford Research, Sioux Falls, South Dakota, United States of America * [email protected] a1111111111 Abstract a1111111111 a1111111111 The Rad50 Interacting Protein 1 (Rint1) influences cellular homeostasis through mainte- a1111111111 nance of endoplasmic reticulum, Golgi and centrosome integrity and regulation of vesicle a1111111111 transport, autophagy and the G2/M checkpoint. Rint1 has been postulated to function as a tumor suppressor as well as an oncogene, with its role depending perhaps upon the precise cellular and/or experimental context. In humans, heterozygosity for germline missense vari- ants in RINT1 have, in some studies, been associated with increased risk of both breast and OPEN ACCESS Lynch syndrome type cancers. However, it is not known if these germline variants represent Citation: Otterpohl KL, Gould KA (2017) Evaluation loss of function alleles or gain of function alleles. Based upon these findings, as well as our of Rint1 as a modifier of intestinal tumorigenesis initial consideration of Rint1 as a potential candidate for Mom5, a genetic modifier of intesti- and cancer risk. PLoS ONE 12(3): e0172247. Min/+ doi:10.1371/journal.pone.0172247 nal tumorigenesis in Apc mice, we sought to explicitly examine the impact of Rint1 on tumorigenesis in ApcMin/+ mice. However, heterozygosity for a knockout of Rint1 had no Editor: Alvaro Galli, CNR, ITALY impact on tumorigenesis in Rint1+/-; ApcMin/+ mice. -
The FEM R Package: Identification of Functional Epigenetic Modules
The FEM R package: Identification of Functional Epigenetic Modules Yinming Jiao and Andrew E. Teschendorff April 24, 2017 1 Summary This vignette provides examples of how to use the package FEM to identify interactome hotspots of differential promoter methylation and differential ex- pression, where an inverse association between promoter methylation and gene expression is assumed [1]. By \interactome hotspot" we mean a connected sub- network of the protein interaction network (PIN) with an exceptionally large average edge-weight density in relation to the rest of the network. The weight edges are constructed from the statistics of association of DNA methylation and gene expression with the phenotype of interest. Thus, the FEM algorithm can be viewed as a functional supervised algorithm, which uses a network of relations between genes (in our case a PPI network), to identify subnetworks where a significant number of genes are associated with a phenotype of interest (POI). We call these \hotspots" also Functional Epigenetic Modules (FEMs). Current functionality of FEM works for Illumina Infinium 450k data, how- ever, the structure is modular allowing easy application or generalization to DNA methylation data generated with other technologies. The FEM algorithm on Illumina 27k data was first presented in [2], with its extension to Illumina 450k data described in [1]. The module detection algorithm used is the spin- glass algorithm of [3]. The PIN used in this vignette includes only protein- protein interactions, derives from Pathway Commons [4] and is available from http://sourceforge.net/projects/funepimod/files under filename hprdAsigH*.Rd, but the user is allowed to specify his own network.