Indian Journal for the Practicing Doctor Vol 7 Issue 1
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Educational Paper Ciliopathies
Eur J Pediatr (2012) 171:1285–1300 DOI 10.1007/s00431-011-1553-z REVIEW Educational paper Ciliopathies Carsten Bergmann Received: 11 June 2011 /Accepted: 3 August 2011 /Published online: 7 September 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Cilia are antenna-like organelles found on the (NPHP) . Ivemark syndrome . Meckel syndrome (MKS) . surface of most cells. They transduce molecular signals Joubert syndrome (JBTS) . Bardet–Biedl syndrome (BBS) . and facilitate interactions between cells and their Alstrom syndrome . Short-rib polydactyly syndromes . environment. Ciliary dysfunction has been shown to Jeune syndrome (ATD) . Ellis-van Crefeld syndrome (EVC) . underlie a broad range of overlapping, clinically and Sensenbrenner syndrome . Primary ciliary dyskinesia genetically heterogeneous phenotypes, collectively (Kartagener syndrome) . von Hippel-Lindau (VHL) . termed ciliopathies. Literally, all organs can be affected. Tuberous sclerosis (TSC) . Oligogenic inheritance . Modifier. Frequent cilia-related manifestations are (poly)cystic Mutational load kidney disease, retinal degeneration, situs inversus, cardiac defects, polydactyly, other skeletal abnormalities, and defects of the central and peripheral nervous Introduction system, occurring either isolated or as part of syn- dromes. Characterization of ciliopathies and the decisive Defective cellular organelles such as mitochondria, perox- role of primary cilia in signal transduction and cell isomes, and lysosomes are well-known -
High-Throughput Discovery of Novel Developmental Phenotypes
High-throughput discovery of novel developmental phenotypes The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Dickinson, M. E., A. M. Flenniken, X. Ji, L. Teboul, M. D. Wong, J. K. White, T. F. Meehan, et al. 2016. “High-throughput discovery of novel developmental phenotypes.” Nature 537 (7621): 508-514. doi:10.1038/nature19356. http://dx.doi.org/10.1038/nature19356. Published Version doi:10.1038/nature19356 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071918 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nature. Manuscript Author Author manuscript; Manuscript Author available in PMC 2017 March 14. Published in final edited form as: Nature. 2016 September 22; 537(7621): 508–514. doi:10.1038/nature19356. High-throughput discovery of novel developmental phenotypes A full list of authors and affiliations appears at the end of the article. Abstract Approximately one third of all mammalian genes are essential for life. Phenotypes resulting from mouse knockouts of these genes have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5000 knockout mouse lines, we have identified 410 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms #Corresponding author: [email protected]. -
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. -
“The Impact of ART on Genome‐Wide Oxidation of 5‐Methylcytosine and the Transcriptome During Early Mouse Development”
“The impact of ART on genome‐wide oxidation of 5‐methylcytosine and the transcriptome during early mouse development” Dissertation zur Erlangung des Grades “Doktor der Naturwissenschaften” am Fachbereich Biologie der Johannes Gutenberg-Universität Mainz Elif Diken geb. Söğütcü geb. am 22.07.1987 in Giresun-TURKEY Mainz 2016 Dekan: 1. Berichterstatter: 2. Berichterstatter: Tag der mündlichen Prüfung: Summary Summary The use of assisted reproductive technologies (ART) has been increasing over the past three decades due to the elevated frequency of infertility problems. Other factors such as easier access to medical aid than in the past and its coverage by health insurance companies in many developed countries also contributed to this growing interest. Nevertheless, a negative impact of ART on transcriptome and methylation reprogramming is heavily discussed. Methylation reprogramming directly after fertilization manifests itself as genome-wide DNA demethylation associated with the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in the pronuclei of mouse zygotes. To investigate the possible impact of ART particularly on this process and the transcriptome in general, pronuclear stage mouse embryos obtained upon spontaneous ovulation or superovulation through hormone stimulation representing ART were subjected to various epigenetic analyses. A whole- transcriptome RNA-Seq analysis of pronuclear stage embryos from spontaneous and superovulated matings demonstrated altered expression of the Bbs12 gene known to be linked to Bardet-Biedl syndrome (BBS) as well as the Dhx16 gene whose zebrafish ortholog was reported to be a maternal effect gene. Immunofluorescence staining with antibodies against 5mC and 5hmC showed that pronuclear stage embryos obtained by superovulation have an increased incidence of abnormal methylation and hydroxymethylation patterns in both maternal and paternal pronuclear DNA compared to their spontaneously ovulated counterparts. -
Knockdown of the BBS10 Gene Product
ndrom Sy es tic & e G n e e n G e f T o Zacchia et al., J Genet Syndr Gene Ther 2014, 5:3 Journal of Genetic Syndromes h l e a r n a DOI: 10.4172/2157-7412.1000222 r p u y o J ISSN: 2157-7412 & Gene Therapy Research Article Open Access Knockdown of the BBS10 Gene Product Affects Apical Targeting of AQP2 in Renal Cells: A Possible Explanation for the Polyuria Associated with Bardet-Biedl Syndrome Miriam Zacchia1, Gabriella Esposito2,3, Monica Carmosino7, Claudia Barbieri7, Enza Zacchia1,5, Alessia Anna Crispo2, Tiziana Fioretti2,3, Francesco Trepiccione1, Valentina Di Iorio6, Francesca Simonelli6, Francesco Salvatore2,4, Giovambattista Capasso1, Maria Svelto7,8 and Giuseppe Procino7,8* 1Chair of Nephrology, Second University of Naples, Italy 2CEINGE-Biotecnologie Avanzate s.c. a r.l., Naples, Italy 3Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Italy 4IRCCS SDN Foundation Naples, Italy 5Institute of Genetics and Biophysics of the National Research Council (CNR), Naples, Italy 6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences - Second University of Naples, Italy 7Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy 8Center of Excellence in Comparative Genomics, Bari, Italy Abstract Objective: Bardet-Biedl syndrome (BBS) is a rare genetic disorder whose clinical features include renal abnormalities, which ranges from renal malformations to renal failure. Polyuria and iso-hyposthenuria are common renal dysfunctions in BBS patients even in the presence of normal GFR. The mechanism underlying this defect is unknown and no genotype-phenotype correlation has yet been reported. -
Whole Exome Sequencing Identifies Causative Mutations in the Majority of Consanguineous Or Familial Cases with Childhood-Onset I
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Kidney Manuscript Author Int. Author manuscript; Manuscript Author available in PMC 2016 August 01. Published in final edited form as: Kidney Int. 2016 February ; 89(2): 468–475. doi:10.1038/ki.2015.317. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood- onset increased renal echogenicity Daniela A. Braun#1, Markus Schueler#1, Jan Halbritter1, Heon Yung Gee1, Jonathan D. Porath1, Jennifer A. Lawson1, Rannar Airik1, Shirlee Shril1, Susan J. Allen2, Deborah Stein1, Adila Al Kindy3, Bodo B. Beck4, Nurcan Cengiz5, Khemchand N. Moorani6, Fatih Ozaltin7,8,9, Seema Hashmi10, John A. Sayer11, Detlef Bockenhauer12, Neveen A. Soliman13,14, Edgar A. Otto2, Richard P. Lifton15,16,17, and Friedhelm Hildebrandt1,17 1Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA 2Department of Pediatrics, University of Michigan, Michigan, USA 3Department of Genetics, Sultan Qaboos University Hospital, Sultanate of Oman 4Institute for Human Genetics, University of Cologne, Germany 5Baskent University, School of Medicine, Adana Medical Training and Research Center, Department of Pediatric Nephrology, Adana, Turkey 6Department of Pediatric Nephrology, National Institute of Child Health, Karachi 75510, Pakistan 7Faculty of Medicine, Department of Pediatric Nephrology, Hacettepe University, Ankara, Turkey 8Nephrogenetics Laboratory, Faculty of Medicine, -
BBS6, BBS10, and BBS12 Form a Complex with CCT/Tric Family Chaperonins and Mediate Bbsome Assembly
BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly Seongjin Seoa,c, Lisa M. Bayeb, Nathan P. Schulza,c, John S. Becka,c, Qihong Zhanga,c, Diane C. Slusarskib, and Val C. Sheffielda,c,1 aDepartment of Pediatrics, bDepartment of Biology, and cHoward Hughes Medical Institute, University of Iowa, Iowa City, IA 52242 Edited by Kathryn V. Anderson, Sloan-Kettering Institute, New York, NY, and approved November 25, 2009 (received for review September 9, 2009) Bardet-Biedl syndrome (BBS) is a human genetic disorder resulting one component of the BBSome, BBS1, directly interacts with the in obesity, retinal degeneration, polydactyly, and nephropathy. leptin receptor and that leptin signaling is attenuated in BBS Recent studies indicate that trafficking defects to the ciliary mem- gene knockout mice, implicating BBS function in a broad range brane are involved in this syndrome. Here, we show that a novel of membrane receptor signaling (33). complex composed of three chaperonin-like BBS proteins (BBS6, Three of the remaining BBS proteins (BBS6, BBS10, and BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBS12) have sequence homology to the CCT (also known as BBSome assembly, which transports vesicles to the cilia. Chaperonin- TRiC) family of group II chaperonins (17, 24, 25). CCT proteins like BBS proteins interact with a subset of BBSome subunits and form an ≈900 kDa hetero-oligomeric complex that mediates promote their association with CCT chaperonins. CCT activity is protein folding in an ATP-dependent manner (34, 35). The CCT essential for BBSome assembly, and knockdown of CCT chaperonins complex consists of two stacked rings, each of which is composed in zebrafish results in BBS phenotypes. -
UC San Francisco Previously Published Works
UCSF UC San Francisco Previously Published Works Title FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease. Permalink https://escholarship.org/uc/item/91k8p2km Journal Genome biology, 9(12) ISSN 1474-7596 Authors Chen, Rong Morgan, Alex A Dudley, Joel et al. Publication Date 2008 DOI 10.1186/gb-2008-9-12-r170 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Open Access Research2008ChenetVolume al. 9, Issue 12, Article R170 FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease Rong Chen*†‡, Alex A Morgan*†‡, Joel Dudley*†‡, Tarangini Deshpande§, Li Li†, Keiichi Kodama*†‡, Annie P Chiang*†‡ and Atul J Butte*†‡ Addresses: *Stanford Center for Biomedical Informatics Research, 251 Cmpus Drive, Stanford, CA 94305, USA. †Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. ‡Lucile Packard Children's Hospital, 725 Welch Road, Palo Alto, CA 94304, USA. §NuMedii Inc., Menlo Park, CA 94025, USA. Correspondence: Atul J Butte. Email: [email protected] Published: 5 December 2008 Received: 17 June 2008 Revised: 26 September 2008 Genome Biology 2008, 9:R170 (doi:10.1186/gb-2008-9-12-r170) Accepted: 5 December 2008 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2008/9/12/R170 © 2008 Chen et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -
README Version Is Dedicated to the Human Genome
AnnotSV Manual Version 3.0.7 AnnotSV is a program for annotating and ranking structural variations from genomes of several organisms. This README version is dedicated to the human genome. https://lbgi.fr/AnnotSV/ Copyright (C) 2017-2021 GEOFFROY Véronique Please feel free to contact me for any suggestions or bug reports email: [email protected] AnnotSV documentation 2021/04/26 1 LEXIQUE 1000g: 1000 Genomes Project (phase 3) ACMG: American College of Medical Genetics and Genomics BED: Browser Extensible Data bp: base pair CDS: CoDing Sequence CNV: Copy Number Variation DDD: Deciphering Developmental Disorders DECIPHER: DatabasE of genomic varIation and Phenotype in Humans using Ensembl Resources DEL: Deletion DGV: Database of Genomic Variants DNA: DesoxyriboNucleic Acid DUP: Duplication ENCODE: Encyclopedia of DNA Elements ExAC: Exome Aggregation Consortium GH: GeneHancer GRCh37: Genome Reference Consortium Human Build 37 GRCh38: Genome Reference Consortium Human Build 38 HI: Haploinsufficiency hom: homozygous htz: heterozygous ID: Identifier indel: Insertion/deletion INS: Insertion INV: Inversion LoF: Loss of Function MCNV: multiallelic CNV MEI: Mobile Element Insertion misZ = Z scoreindicating gene intolerance to missense variation NAHR: Non-Allelic Homologous Recombination OMIM: Online Mendelian Inheritance in Man pLI: score indicating gene intolerance to a loss of function variation SNV: Single Nucleotide Variation SV: Structural Variations synZ = Z score indicating gene intolerance to synonymous variation TAD: Topologically -
BBS6, BBS10, and BBS12 Form a Complex with CCT/Tric Family Chaperonins and Mediate Bbsome Assembly
BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly Seongjin Seoa,c, Lisa M. Bayeb, Nathan P. Schulza,c, John S. Becka,c, Qihong Zhanga,c, Diane C. Slusarskib, and Val C. Sheffielda,c,1 aDepartment of Pediatrics, bDepartment of Biology, and cHoward Hughes Medical Institute, University of Iowa, Iowa City, IA 52242 Edited by Kathryn V. Anderson, Sloan-Kettering Institute, New York, NY, and approved November 25, 2009 (received for review September 9, 2009) Bardet-Biedl syndrome (BBS) is a human genetic disorder resulting one component of the BBSome, BBS1, directly interacts with the in obesity, retinal degeneration, polydactyly, and nephropathy. leptin receptor and that leptin signaling is attenuated in BBS Recent studies indicate that trafficking defects to the ciliary mem- gene knockout mice, implicating BBS function in a broad range brane are involved in this syndrome. Here, we show that a novel of membrane receptor signaling (33). complex composed of three chaperonin-like BBS proteins (BBS6, Three of the remaining BBS proteins (BBS6, BBS10, and BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBS12) have sequence homology to the CCT (also known as BBSome assembly, which transports vesicles to the cilia. Chaperonin- TRiC) family of group II chaperonins (17, 24, 25). CCT proteins like BBS proteins interact with a subset of BBSome subunits and form an ≈900 kDa hetero-oligomeric complex that mediates promote their association with CCT chaperonins. CCT activity is protein folding in an ATP-dependent manner (34, 35). The CCT essential for BBSome assembly, and knockdown of CCT chaperonins complex consists of two stacked rings, each of which is composed in zebrafish results in BBS phenotypes. -
Cystic Kidney Diseases and During Vertebrate Gastrulation
Pediatr Nephrol (2011) 26:1181–1195 DOI 10.1007/s00467-010-1697-5 REVIEW Cystic diseases of the kidney: ciliary dysfunction and cystogenic mechanisms Cecilia Gascue & Nicholas Katsanis & Jose L. Badano Received: 3 August 2010 /Revised: 15 September 2010 /Accepted: 15 October 2010 /Published online: 27 November 2010 # IPNA 2010 Abstract Ciliary dysfunction has emerged as a common Introduction factor underlying the pathogenesis of both syndromic and isolated kidney cystic disease, an observation that has Cystic diseases of the kidney are a significant contributor to contributed to the unification of human genetic disorders of renal malformations and a common cause of end stage renal the cilium, the ciliopathies. Such grouping is underscored disease (ESRD). This classification encompasses a number by two major observations: the fact that genes encoding of human disorders that range from conditions in which ciliary proteins can contribute causal and modifying cyst formation is either the sole or the main clinical mutations across several clinically discrete ciliopathies, manifestation, to pleiotropic syndromes where cyst forma- and the emerging realization that an understanding of the tion is but one of the observed pathologies, exhibits clinical pathology of one ciliopathy can provide valuable variable penetrance, and can sometimes be undetectable insight into the pathomechanism of renal cyst formation until later in life or upon necropsy (Table 1;[1]). elsewhere in the ciliopathy spectrum. In this review, we Importantly, although the different cystic kidney disorders discuss and attempt to stratify the different lines of are clinically discrete entities, an extensive body of data proposed cilia-driven mechanisms for cystogenesis, ranging fueled by a combination of mutation identification in from mechano- and chemo-sensation, to cell shape and humans and studies in animal models suggests a common polarization, to the transduction of a variety of signaling thread, where virtually all known renal cystic disease- cascades. -
Biomédica 2018;38:451-2 Biomédica Revista Del Instituto Nacional De Salud Volumen 38, No
I-ISSN 2590-7379 (En línea) Biomédica 2018;38:451-2 Biomédica Revista del Instituto Nacional de Salud Volumen 38, No. 3 - Septiembre de 2018 Bogotá, D.C., Colombia, S.A. 452 Portada: 0 304 Biomédica Instituto Nacional de Salud Volumen 38, No. 3 - Bogotá, D.C., Colombia - Septiembre de 2018 Comité Editorial EDITORES LUIS ALBERTO GÓMEZ CARLOS ARTURO HERNÁNDEZ RUBÉN SANTIAGO NICHOLLS Instituto Nacional de Salud Instituto Nacional de Salud Organización Panamericana de la Salud Bogotá, D.C., Colombia Bogotá, D.C., Colombia Washington, D.C., Estados Unidos EDITORES ASOCIADOS ENRIQUE ARDILA LEONARD MUNSTERMANN Bogotá, D.C., Colombia Yale University School of Medicine New Haven, CT, Estados Unidos JOSÉ DE JESÚS MORENO-MONTOYA Universidad El Bosque OMAR SEGURA Bogotá, D.C., Colombia Federación Médica Colombiana Bogotá, D.C., Colombia JULIÁN ALFREDO FERNÁNDEZ-NIÑO Universidad del Norte ORLANDO TORRES-FERNÁNDEZ Barranquilla, Colombia Instituto Nacional de Salud Bogotá, D.C., Colombia MIGUEL A. GUZMÁN Investigador Emérito RAÚL PARDO Instituto Nacional de Salud Instituto Nacional de Salud Bogotá, D.C., Colombia Bogotá, D.C., Colombia Comité Científico ARNOLDO BARBOSA ANDRÉS DE FRANCISCO JOHN MARIO GONZÁLEZ Universidad del Tolima Organización Mundial de la Salud Universidad de los Andes Ibagué, Colombia Ginebra, Suiza Bogotá, D.C., Colombia ANTONIO BERMÚDEZ FERNANDO DE LA HOZ FELIPE GUHL Instituto Nacional de Salud Universidad Nacional de Colombia Universidad