CUBN Is a Gene Locus for Albuminuria
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Structure, Function and Five Basic Needs of the Global Health Research System
Edinburgh Research Explorer Structure, function and five basic needs of the global health research system Citation for published version: Rudan, I & Sridhar, D 2016, 'Structure, function and five basic needs of the global health research system', Journal of Global Health, vol. 6, no. 1, pp. 010505. https://doi.org/10.7189/jogh.06.010505 Digital Object Identifier (DOI): 10.7189/jogh.06.010505 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Journal of Global Health Publisher Rights Statement: Copyright © 2016 by the Journal of Global Health. All rights reserved. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download -
Exome Sequencing Reveals Cubilin Mutation As a Single-Gene Cause of Proteinuria
BRIEF COMMUNICATION www.jasn.org Exome Sequencing Reveals Cubilin Mutation as a Single-Gene Cause of Proteinuria Bugsu Ovunc,*† Edgar A. Otto,* Virginia Vega-Warner,* Pawaree Saisawat,* Shazia Ashraf,* Gokul Ramaswami,* Hanan M. Fathy,‡ Dominik Schoeb,* Gil Chernin,* Robert H. Lyons,§ ʈ Engin Yilmaz,† and Friedhelm Hildebrandt* ¶ ʈ Departments of *Pediatrics and Human Genetics, §Department of Biological Chemistry and DNA Sequencing Core, and ¶Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan; †Department of Medical Biology, Hacettepe University, Ankara, Turkey; and ‡The Pediatric Nephrology Unit, Alexandria University, Alexandria, Egypt ABSTRACT In two siblings of consanguineous parents with intermittent nephrotic-range pro- tion is still unknown.7 This forbids the use of teinuria, we identified a homozygous deleterious frameshift mutation in the gene cohort studies for gene identification and ne- CUBN, which encodes cubulin, using exome capture and massively parallel re- cessitates the ability to identify disease-caus- sequencing. The mutation segregated with affected members of this family and ing genes in single families. We therefore was absent from 92 healthy individuals, thereby identifying a recessive mutation in combined whole genome homozygosity CUBN as the single-gene cause of proteinuria in this sibship. Cubulin mutations mapping with consecutive whole human ex- cause a hereditary form of megaloblastic anemia secondary to vitamin B12 defi- ome capture (WHEC) and massively par- ciency, and proteinuria occurs in 50% of cases since cubilin is coreceptor for both allel re-sequencing to overcome this lim- 6 the intestinal vitamin B12-intrinsic factor complex and the tubular reabsorption of itation. In this way we here identify a protein in the proximal tubule. -
Detailed Investigations of Proximal Tubular Function in Imerslund-Grasbeck Syndrome
Detailed investigations of proximal tubular function in Imerslund-Grasbeck syndrome. Tina Storm, Christina Zeitz, Olivier Cases, Sabine Amsellem, Pierre Verroust, Mette Madsen, Jean-François Benoist, Sandrine Passemard, Sophie Lebon, Iben Jønsson, et al. To cite this version: Tina Storm, Christina Zeitz, Olivier Cases, Sabine Amsellem, Pierre Verroust, et al.. Detailed in- vestigations of proximal tubular function in Imerslund-Grasbeck syndrome.. BMC Medical Genetics, BioMed Central, 2013, 14 (1), pp.111. 10.1186/1471-2350-14-111. inserm-00904107 HAL Id: inserm-00904107 https://www.hal.inserm.fr/inserm-00904107 Submitted on 13 Nov 2013 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. Storm et al. BMC Medical Genetics 2013, 14:111 http://www.biomedcentral.com/1471-2350/14/111 RESEARCHARTICLE Open Access Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome Tina Storm1, Christina Zeitz2,3,4, Olivier Cases2,3,4, Sabine Amsellem2,3,4, Pierre J Verroust1,2,3,4, Mette Madsen1, Jean-François Benoist6, Sandrine Passemard7,8, Sophie Lebon8, Iben Møller Jønsson9, Francesco Emma10, Heidi Koldsø11, Jens Michael Hertz12, Rikke Nielsen1, Erik I Christensen1* and Renata Kozyraki2,3,4,5* Abstract Background: Imerslund-Gräsbeck Syndrome (IGS) is a rare genetic disorder characterised by juvenile megaloblastic anaemia. -
Detailed Investigations of Proximal Tubular Function in Imerslund-Gräsbeck Syndrome
Storm et al. BMC Medical Genetics 2013, 14:111 http://www.biomedcentral.com/1471-2350/14/111 RESEARCH ARTICLE Open Access Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome Tina Storm1, Christina Zeitz2,3,4, Olivier Cases2,3,4, Sabine Amsellem2,3,4, Pierre J Verroust1,2,3,4, Mette Madsen1, Jean-François Benoist6, Sandrine Passemard7,8, Sophie Lebon8, Iben Møller Jønsson9, Francesco Emma10, Heidi Koldsø11, Jens Michael Hertz12, Rikke Nielsen1, Erik I Christensen1* and Renata Kozyraki2,3,4,5* Abstract Background: Imerslund-Gräsbeck Syndrome (IGS) is a rare genetic disorder characterised by juvenile megaloblastic anaemia. IGS is caused by mutations in either of the genes encoding the intestinal intrinsic factor-vitamin B12 receptor complex, cubam. The cubam receptor proteins cubilin and amnionless are both expressed in the small intestine as well as the proximal tubules of the kidney and exhibit an interdependent relationship for post-translational processing and trafficking. In the proximal tubules cubilin is involved in the reabsorption of several filtered plasma proteins including vitamin carriers and lipoproteins. Consistent with this, low-molecular-weight proteinuria has been observed in most patients with IGS. The aim of this study was to characterise novel disease-causing mutations and correlate novel and previously reported mutations with the presence of low-molecular-weight proteinuria. Methods: Genetic screening was performed by direct sequencing of the CUBN and AMN genes and novel identified mutations were characterised by in silico and/or in vitro investigations. Urinary protein excretion was analysed by immunoblotting and high-resolution gel electrophoresis of collected urines from patients and healthy controls to determine renal phenotype. -
Genetic Comparison of a Croatian Isolate and CEPH European Founders
Edinburgh Research Explorer Genetic comparison of a Croatian isolate and CEPH European founders Citation for published version: Navarro, P, Vitart, V, Hayward, C, Tenesa, A, Zgaga, L, Juricic, D, Polasek, O, Hastie, ND, Rudan, I, Campbell, H, Wright, AF, Haley, CS & Knott, SA 2010, 'Genetic comparison of a Croatian isolate and CEPH European founders', Genetic Epidemiology, vol. 34, no. 2, pp. 140-5. https://doi.org/10.1002/gepi.20443 Digital Object Identifier (DOI): 10.1002/gepi.20443 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Genetic Epidemiology General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 29. Sep. 2021 Genetic Epidemiology 34 : 140–145 (2010) Genetic Comparison of a Croatian Isolate and CEPH European Founders Pau Navarro,1Ã Ve´ronique Vitart,1 Caroline Hayward,1 Albert Tenesa,2 Lina Zgaga,3 Danica Juricic,4 Ozren Polasek,3,5 Nicholas D. Hastie,1 Igor Rudan,5,6 Harry Campbell,5 Alan F. -
Gene Expression Analysis Defines the Proximal Tubule As the Compartment for Endocytic Receptor-Mediated Uptake in the Xenopus Pronephric Kidney
Pflugers Arch - Eur J Physiol (2008) 456:1163–1176 DOI 10.1007/s00424-008-0488-3 MOLECULAR AND GENOMIC PHYSIOLOGY Gene expression analysis defines the proximal tubule as the compartment for endocytic receptor-mediated uptake in the Xenopus pronephric kidney Erik I. Christensen & Daniela Raciti & Luca Reggiani & Pierre J. Verroust & André W. Brändli Received: 16 January 2008 /Accepted: 28 February 2008 /Published online: 13 June 2008 # Springer-Verlag 2008 Abstract Endocytic receptors in the proximal tubule of the lrp2 and cubilin in the apical plasma membrane. Further- mammalian kidney are responsible for the reuptake of more, functional aspects of the endocytic receptors were numerous ligands, including lipoproteins, sterols, vitamin- revealed by the vesicular localization of retinol-binding binding proteins, and hormones, and they can mediate protein in the proximal tubules, probably representing drug-induced nephrotoxicity. In this paper, we report the endocytosed protein. In summary, we provide here the first first evidence indicating that the pronephric kidneys of comprehensive report of endocytic receptor expression, Xenopus tadpoles are capable of endocytic transport. We including amnionless, in a nonmammalian species. Re- establish that the Xenopus genome harbors genes for the markably, renal endocytic receptor expression and function known three endocytic receptors megalin/LRP2, cubilin, in the Xenopus pronephric kidney closely mirrors the and amnionless. The Xenopus endocytic receptor genes situation in the mammalian kidney. The Xenopus proneph- share extensive synteny with their mammalian counterparts. ric kidney therefore represents a novel, simple model for In situ hybridizations demonstrated that endocytic receptor physiological studies on the molecular mechanisms under- expression is highly tissue specific, primarily in the lying renal tubular endocytosis. -
Genetic Heterogeneity of Megaloblastic Anaemia Type 1 in Tunisian Patients
J Hum Genet (2007) 52:262–270 DOI 10.1007/s10038-007-0110-0 ORIGINAL ARTICLE Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients Chiraz Bouchlaka Æ Chokri Maktouf Æ Bahri Mahjoub Æ Abdelkarim Ayadi Æ M. Tahar Sfar Æ Mahbouba Sioud Æ Neji Gueddich Æ Zouheir Belhadjali Æ Ahmed Rebaı¨ Æ Sonia Abdelhak Æ Koussay Dellagi Received: 2 August 2006 / Accepted: 21 December 2006 / Published online: 7 February 2007 Ó The Japan Society of Human Genetics and Springer 2007 Abstract Megaloblastic anaemia 1 (MGA1) is a rare geneous and can be caused by mutations in either the autosomal recessive condition characterized by selec- cubilin (CUBN) or the amnionless (AMN) gene. In tive intestinal vitamin B12 malabsorption and pro- the present study we investigated the molecular defect teinuria. More than 200 MGA1 patients have been underlying MGA1 in nine Tunisian patients belonging identified worldwide, but the disease is relatively to six unrelated consanguineous families. Haplotype prevalent in Finland, Norway and several Eastern and linkage analyses, using microsatellite markers Mediterranean regions. MGA1 is genetically hetero- surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these fami- C. Bouchlaka Á C. Maktouf Á S. Abdelhak (&) lies were screened for the Finnish, Mediterranean and Molecular Investigation of Genetic Orphan Diseases, Arabian mutations already published. None of the Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, screened mutations could be detected in our popula- Tunis Belve´de`re, Tunisia tion. One family showed a linkage to AMN gene. -
Demonstrating Reduced Environmental and Genetic Diversity in Human Isolates by Analysis of Blood Lipid Levels
View metadata, citation and similar papers at core.ac.uk brought to you by CORE Brief Report Demonstrating Reduced Environmental and Genetic Diversity in Human Isolates by Analysis of Blood Lipid Levels Ozren Polašek1,2, Ivana Kolčić1, Ankica Smoljanović3, Dražen Stojanović4, Matijana Grgić5, Barbara Ebling6, Maja Klarić6, Josip Milas6, Dinko Puntarić6 1Department of Medical Statistics, Aim To test the hypothesis that phenotypic diversity in isolated hu- Epidemiology, and Medical Informatics, man populations is decreased in comparison with general outbred Andrija Štampar School of Public Health, population because of reduced genetic and environmental diversity. Zagreb University School of Medicine, Zagreb, Croatia; To demonstrate this in populations for which reduced genetic and 2Department of Public Health Sciences, environmental diversity had already been established, by studying the University of Edinburgh, Edinburgh, UK amount of variation in plasma lipid levels. 3 Institute of Public Health, Split, Croatia Methods Fasting plasma lipid levels (cholesterol, triglycerides, low 4Department of Epidemiology, Rijeka density lipoprotein [LDL], and high density lipoprotein [HDL]) were University School of Medicine, measured in randomly selected 300 inhabitants from 2 isolated hu- Rijeka, Croatia man populations, the island of Rab and the neighboring islands of Vis 5Institute of Public Health, and Lastovo, Croatia. The populations were chosen based on previous Zagreb, Croatia analyses of genetic diversity and lifestyle patterns, which were shown 6Department of Epidemiology, Osijek University School of Medicine, to be both less diverse and more uniform than the general Croatian Osijek, Croatia population. We studied whether the 25’-75’ and 5′-95’ interpercentile ranges in observed values were consistently smaller in 2 samples of 300 examinees from isolated populations in comparison with nearly 6000 examinees from an earlier study who were demographically targeted to > Correspondence to: represent the larger Croatian population. -
Following Abstracts Were Not Provided I Onda Ih
Impressum PUBLISHER: ISABS – International Society for Applied Biological Sciences CIRCULATION: 500 copies Zagreb, June 2011 Copyright 2011 Video and/or audio-taping of any session is not permitted without prior approval from the speakers and from the scientific committee of the 7th ISABS Conference in Forensic, Anthropologic and Medical Genetics and Mayo Clinic Lectures in Translational Medicine 7th ISABS Conference in Forensic, Anthropologic and Medical Genetics and Mayo Clinic Lectures in Translational Medicine 1 June 20-24, 2011, Bol, Island of Braþ, Croatia Conference floor layout Braè Executive bar Press center WC Hvar Šolta Korèula WC Entrance Bar Ela Vis Souvenir shop Reception Restaurant Wellness Bowling Tavern “Vallum” Night club 7th ISABS Conference in Forensic, Anthropologic and Medical Genetics and Mayo Clinic Lectures in Translational Medicine 2 June 20-24, 2011, Bol, Island of Braþ, Croatia Table of Contents Table of Contents Welcome note …………………………………………………. 4 Conference Organizer ……………………………………….. 5 ISABS Committees …………………………………………… 7 The Young Investigator Awards…….. ……………………... 10 Scientific Program Information …………………………….. 11 General Information ………………………………………….. 13 Speakers ……………………………………………………….. 15 Scientific Program ……………………………………………. 20 Abstracts – Oral Presentations ……………………………. 30 Invited Lectures ………………………………………………… 31 Technial Workshop………………………………………………87 Selected Lectures ……………………………………………… 91 YIA ……………………………………………………………….. 96 Abstracts – Poster Presentations …………………………. 101 Forensic Genetics ……………………………………………… -
M1BP Cooperates with CP190 to Activate Transcription at TAD Borders and Promote Chromatin Insulator Activity
ARTICLE https://doi.org/10.1038/s41467-021-24407-y OPEN M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity Indira Bag 1,2, Shue Chen 1,2,4, Leah F. Rosin 1,2,4, Yang Chen 1,2, Chen-Yu Liu3, Guo-Yun Yu3 & ✉ Elissa P. Lei 1,2 1234567890():,; Genome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP facilitates CP190 chromatin binding at many shared sites and vice versa. Both factors promote Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP reduces chromatin accessibility and increases both inter- and intra-TAD local genome compaction. Our results reveal physical and functional inter- action between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization. 1 Nuclear Organization and Gene Expression Section, Bethesda, MD, USA. 2 Laboratory of Biochemistry and Genetics, Bethesda, MD, USA. 3 Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. ✉ 4These authors contributed equally: Shue Chen, Leah F. -
Article Reference
Article Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels TIN, Adrienne, et al. Abstract Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between [...] Reference TIN, Adrienne, et al. Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels. Nature Genetics, 2019, vol. 51, no. 10, p. 1459-1474 DOI : 10.1038/s41588-019-0504-x PMID : 31578528 Available at: http://archive-ouverte.unige.ch/unige:147158 Disclaimer: layout of this document may differ from the published version. 1 / 1 HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nat Genet Manuscript Author . Author manuscript; Manuscript Author available in PMC 2020 April 02. Published in final edited form as: Nat Genet. -
Where and Why Are 10 Million Children Dying Every Year?
CHILD SURVIVAL I Child survival I Where and why are 10 million children dying every year? Robert E Black, Saul S Morris, Jennifer Bryce More than 10 million children die each year, most from preventable causes and almost all in poor countries. Six countries account for 50% of worldwide deaths in children younger than 5 years, and 42 countries for 90%. The causes of death differ substantially from one country to another, highlighting the need to expand understanding of child health epidemiology at a country level rather than in geopolitical regions. Other key issues include the importance of undernutrition as an underlying cause of child deaths associated with infectious diseases, the effects of multiple concurrent illnesses, and recognition that pneumonia and diarrhoea remain the diseases that are most often associated with child deaths. A better understanding of child health epidemiology could contribute to more effective approaches to saving children’s lives. Substantial reductions in child mortality occurred in low- commensurate with needs. The mortality reduction target income and middle-income countries in the late 20th was reached for only five of 55 countries with an under-5- century, but more than 10 million children younger than year mortality rate of 100 or more in 1990.4 5 years still die every year.1,2 In this article, the first in a In 2002, as part of the millennium development goals series of five, we consider reasons for these deaths and for health, nations pledged to ensure a two-thirds provide recommendations for how they can be prevented. reduction in child mortality by 2015, from the base year Rates of decline in worldwide child mortality peaked in 1990.5 In addition to setting such a goal, the global public about 1980.1 In 1990–2001, the number of child deaths health community must critically assess how it can be fell by 1·1% every year, compared with 2·5% per year accomplished.