Blueprint Genetics Cataract Panel
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Localization of the Lens Intermediate Filament Switch by Imaging Mass Spectrometry
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.21.053793; this version posted April 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Localization of the Lens Intermediate Filament Switch by Imaging Mass Spectrometry Zhen Wang, Daniel J. Ryan, and Kevin L Schey* Department of Biochemistry, Vanderbilt University, Nashville, TN 37232 * To whom correspondence should be addressed Current address: Mass Spectrometry Research Center Vanderbilt University 465 21st Ave. So., Suite 9160 MRB III Nashville, TN 37232-8575 E-mail: [email protected] Phone: 615.936.6861 Fax: 615.343.8372 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.21.053793; this version posted April 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Imaging mass spectrometry (IMS) enables targeted and untargeted visualization of the spatial localization of molecules in tissues with great specificity. The lens is a unique tissue that contains fiber cells corresponding to various stages of differentiation that are packed in a highly spatial order. The application of IMS to lens tissue localizes molecular features that are spatially related to the fiber cell organization. Such spatially resolved molecular information assists our understanding of lens structure and physiology; however, protein IMS studies are typically limited to abundant, soluble, low molecular weight proteins. In this study, a method was developed for imaging low solubility cytoskeletal proteins in the lens; a tissue that is filled with high concentrations of soluble crystallins. -
Whole Exome Sequencing Gene Package Vision Disorders, Version 6.1, 31-1-2020
Whole Exome Sequencing Gene package Vision disorders, version 6.1, 31-1-2020 Technical information DNA was enriched using Agilent SureSelect DNA + SureSelect OneSeq 300kb CNV Backbone + Human All Exon V7 capture and paired-end sequenced on the Illumina platform (outsourced). The aim is to obtain 10 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate and non-unique reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA-MEM algorithm (reference: http://bio-bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x ABCA4 Cone-rod dystrophy 3, 604116 601691 94 100 100 97 Fundus flavimaculatus, 248200 {Macular degeneration, age-related, 2}, 153800 Retinal dystrophy, early-onset severe, 248200 Retinitis pigmentosa 19, 601718 Stargardt disease -
A Comprehensive Analysis of the Expression of Crystallins in Mouse Retina Jinghua Xi Washington University School of Medicine in St
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2003 A comprehensive analysis of the expression of crystallins in mouse retina Jinghua Xi Washington University School of Medicine in St. Louis Rafal Farjo University of Michigan - Ann Arbor Shigeo Yoshida University of Michigan - Ann Arbor Timothy S. Kern Case Western Reserve University Anand Swaroop University of Michigan - Ann Arbor See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Xi, Jinghua; Farjo, Rafal; Yoshida, Shigeo; Kern, Timothy S.; Swaroop, Anand; and Andley, Usha P., ,"A comprehensive analysis of the expression of crystallins in mouse retina." Molecular Vision.9,. 410-419. (2003). https://digitalcommons.wustl.edu/open_access_pubs/1801 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Jinghua Xi, Rafal Farjo, Shigeo Yoshida, Timothy S. Kern, Anand Swaroop, and Usha P. Andley This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/1801 Molecular Vision 2003; 9:410-9 <http://www.molvis.org/molvis/v9/a53> © 2003 Molecular Vision Received 28 May 2003 | Accepted 19 August 2003 | Published 28 August 2003 A comprehensive analysis of the expression of crystallins in mouse retina Jinghua Xi,1 Rafal Farjo,3 Shigeo Yoshida,3 Timothy S. Kern,5 Anand Swaroop,3,4 Usha P. Andley1,2 Departments of 1Ophthalmology and Visual Sciences and 2Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. -
Related Macular Degeneration and Cutis Laxa
UvA-DARE (Digital Academic Repository) Genetic studies of age-related macular degeneration Baas, D.C. Publication date 2012 Document Version Final published version Link to publication Citation for published version (APA): Baas, D. C. (2012). Genetic studies of age-related macular degeneration. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:05 Oct 2021 G������ S������ �� A��-������� M������ D����������� D����������� M������ G������ S������ �� A��-������� | 2012 D�������� C. B��� G������ S������ �� A��-������� M������ D����������� D�������� C. B��� cover.indd 1 31-10-12 08:36 Genetic Studies of Age-related Macular Degeneration Dominique C. Baas Chapter 0.indd 1 23-10-12 19:24 The research described in this thesis was conducted at the Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Department of Clinical and Molecular Ophthalmogenetics, Amsterdam, The Netherlands. -
Ophthalmology
Ophthalmology Information for health professionals MEDICAL GENETIC TESTING FOR OPHTHALMOLOGY Recent technologies, in particularly Next Generation Sequencing (NGS), allows fast, accurate and valuable diagnostic tests. For Ophthalmology, CGC Genetics has an extensive list of medical genetic tests with clinical integration of results by our Medical Geneticists. 1. EXOME SEQUENCING: Exome Sequencing is a very efficient strategy to study most exons of a patient’s genome, unraveling mutations associated with specific disorders or phenotypes. With this diagnostic strategy, patients can be studied with a significantly reduced turnaround time and cost. CGC Genetics has available 2 options for Exome Sequencing: • Whole Exome Sequencing (WES), which analyzes the entire exome (about 20 000 genes); • Disease Exome by CGC Genetics, which analyzes about 6 000 clinically-relevant genes. Any of these can be performed in the index case or in a Trio. 2. NGS PANELS For NGS panels, several genes associated with the same phenotype are simultaneously sequenced. These panels provide increased diagnostic capability with a significantly reduced turnaround time and cost. CGC Genetics has several NGS panels for Ophthalmology that are constantly updated (www.cgcgenetics.com). Any gene studied in exome or NGS panel can also be individually sequenced and analyzed for deletion/duplication events. 3. EXPERTISE IN MEDICAL GENETICS CGC Genetics has Medical Geneticists specialized in genetic counseling for ophthalmological diseases who may advice in choosing the most appropriate -
Common Variants in SOX-2 and Congenital Cataract Genes Contribute to Age-Related Nuclear Cataract
ARTICLE https://doi.org/10.1038/s42003-020-01421-2 OPEN Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract Ekaterina Yonova-Doing et al.# 1234567890():,; Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this dis- ease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cat- aract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye. #A list of authors and their affiliations appears at the end of the paper. COMMUNICATIONS BIOLOGY | (2020) 3:755 | https://doi.org/10.1038/s42003-020-01421-2 | www.nature.com/commsbio 1 ARTICLE COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-020-01421-2 ge-related cataract is the leading cause of blindness, structure (meta-analysis genomic inflation factor λ = 1.009, accounting for more than one-third of blindness Supplementary Table 4 and Supplementary Fig. -
Congenital Cataracts Due to a Novel 2‑Bp Deletion in CRYBA1/A3
1614 MOLECULAR MEDICINE REPORTS 10: 1614-1618, 2014 Congenital cataracts due to a novel 2‑bp deletion in CRYBA1/A3 JING ZHANG1, YANHUA ZHANG1, FANG FANG1, WEIHONG MU1, NING ZHANG2, TONGSHUN XU3 and QINYING CAO1 1Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital; 2Department of Cardiology, The Second Hospital of Hebei Medical University; 3Department of Surgery, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, Hebei, P.R. China Received September 22, 2013; Accepted April 11, 2014 DOI: 10.3892/mmr.2014.2324 Abstract. Congenital cataracts, which are a clinically and located in the eye lens. The major human crystallins comprise genetically heterogeneous group of eye disorders, lead to 90% of protein in the mature lens and contain two different visual impairment and are a significant cause of blindness superfamilies: the small heat‑shock proteins (α-crystallins) in childhood. A major proportion of the causative mutations and the βγ-crystallins. for congenital cataracts are found in crystallin genes. In the In this study a functional candidate approach was used present study, a novel deletion mutation (c.590-591delAG) in to investigate the known crystallin genes, including CRYAA, exon 6 of CRYBA1/A3 was identified in a large family with CRYAB, CRYBA1/A3, CRYBB1, CRYBB2, CRYGC, CRYGD autosomal dominant congenital cataracts. An increase in and CRYGS, in which a major proportion of the mutations local hydrophobicity was predicted around the mutation site; identified in a large family with congenital cataracts were however, further studies are required to determine the exact found. effect of the mutation on βA1/A3-crystallin structure and function. To the best of our knowledge, this is the first report Subjects and methods of an association between a frameshift mutation in exon 6 of CRYBA1/A3 and congenital cataracts. -
Proteome Profiling of Developing Murine Lens Through Mass
Lens Proteome Profiling of Developing Murine Lens Through Mass Spectrometry Shahid Y. Khan,1 Muhammad Ali,1 Firoz Kabir,1 Santosh Renuse,2 Chan Hyun Na,2 C. Conover Talbot Jr,3 Sean F. Hackett,1 and S. Amer Riazuddin1 1The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States 2Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States 3Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States Correspondence: S. Amer Riazuddin, PURPOSE. We previously completed a comprehensive profile of the mouse lens transcriptome. The Wilmer Eye Institute, Johns Here, we investigate the proteome of the mouse lens through mass spectrometry–based Hopkins University School of Medi- protein sequencing at the same embryonic and postnatal time points. cine, 600 N. Wolfe Street; Maumenee 840, Baltimore, MD 21287, USA; METHODS. We extracted mouse lenses at embryonic day 15 (E15) and 18 (E18) and postnatal [email protected]. day 0 (P0), 3 (P3), 6 (P6), and 9 (P9). The lenses from each time point were preserved in three Submitted: February 2, 2017 distinct pools to serve as biological replicates for each developmental stage. The total cellular Accepted: October 13, 2017 protein was extracted from the lens, digested with trypsin, and labeled with isobaric tandem mass tags (TMT) for three independent TMT experiments. Citation: Khan SY, Ali M, Kabir F, et al. Proteome profiling of developing mu- RESULTS. A total of 5404 proteins were identified in the mouse ocular lens in at least one rine lens through mass spectrometry. -
Basement Membranes in Diseases Affecting the Eye, Kidney
Van Agtmael, T. and Bruckner-Tuderman, L. (2010) Basement membranes and human disease. Cell and Tissue Research, 339 (1). pp. 167-188. ISSN 0302-766X http://eprints.gla.ac.uk/35275/ Deposited on: 30 August 2010 Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Basement membranes and human disease Tom van Agtmael§ and Leena Bruckner-Tuderman* § Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, U.K. and * Dept. of Dermatology, University Medical Center Freiburg and Freiburg Institute for Advanced Studies, Freiburg, Germany Corresponding authors: Tom Van Agtmael Faculty of Biomedical and Life Sciences, Davidson Building, University of Glasgow, University Avenue, Glasgow UK, [email protected],. Leena Bruckner-Tuderman Department of Dermatology, University Medical Center Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. E-mail: [email protected] Keywords: basement membrane, laminin, collagen, laminin, nidogen Abbreviations BM: basement membrane, NMJ neuromuscular junction, DEJ dermo epidermal junction, SJS Schwartz Jampel syndrome, DDSH Dyssegmental dysplasia silverman handmaker type, EB epidermolysis bullosa, GBM glomerular basement membrane 1 Abstract In 1990 the role of basement membranes in human disease was established by the identification of COL4A5 mutations in Alport’s syndrome. Since then the number of diseases caused by mutations in basement membrane components has steadily increased as has our understanding of the roles of basement membranes in organ development and function. However, many questions remain as to the molecular and cellular consequences of these mutations and how they lead to the observed disease phenotypes. Despite this, exciting progress has recently been made with potential treatment options for some of these so far incurable diseases. -
Congenital Eye Disorders Gene Panel
Congenital eye disorders gene panel Contact details Introduction Regional Genetics Service Ocular conditions are highly heterogeneous and show considerable phenotypic overlap. 1 in Levels 4-6, Barclay House 2,500 children in the UK are diagnosed as blind or severely visually impaired by the time they 37 Queen Square reach one year old. As many as half of these cases are likely to be inherited and remain undiagnosed due to the vast number of genes involved in these conditions. Many congenital London, WC1N 3BH eye disorders causing visual impairment or blindness at birth or progressive visual impairment T +44 (0) 20 7762 6888 also include syndromic conditions involving additional metabolic, developmental, physical or F +44 (0) 20 7813 8578 sensory abnormalities. Gene panels offer the enhanced probability of diagnosis as a very large number of genes can be interrogated. Samples required Ocular birth defects include all inheritance modalities. Autosomal dominant and recessive 5ml venous blood in plastic EDTA diseases as well as X-linked dominant and recessive diseases are seen. These conditions can bottles (>1ml from neonates) also be caused by de novo variants. Prenatal testing must be arranged Referrals in advance, through a Clinical Genetics department if possible. Patients presenting with a phenotype appropriate for the requested sub-panel Amniotic fluid or CV samples Referrals will be accepted from clinical geneticists and consultants in ophthalmology. should be sent to Cytogenetics for Prenatal testing dissecting and culturing, with instructions to forward the sample Prenatal diagnosis may be offered as appropriate where pathogenic variants have been to the Regional Molecular Genetics identified in accordance with expected inheritance pattern and where appropriate parental laboratory for analysis testing and counselling has been conducted. -
Inherited Connective Tissue Disorders of Collagens: Lessons from Targeted Mutagenesis
13 Inherited Connective Tissue Disorders of Collagens: Lessons from Targeted Mutagenesis Christelle Bonod-Bidaud and Florence Ruggiero Institut de Génomique Fonctionnelle de Lyon, ENS de Lyon, UMR CNRS 5242, University Lyon 1, France 1. Introduction The extracellular matrix (ECM) is the cell structural environment in tissues and organs. The ECM is a dynamic structure that it is constantly remodelled. It contributes to tissue integrity and mechanical properties. It is also essential for maintaining tissue homeostasis, morphogenesis and differentiation, which it does, through specific interactions with cells. The ECM is composed of a mixture of water and macromolecules classified into four main categories: collagens, proteoglycans, elastic proteins, and non-collagenous glycoproteins (also called adhesive glycoproteins). The nature, concentration and ratio of the different ECM components are all important factors in the regulation of the assembly of complex tissue-specific networks tuned to meet mechanical and biological requirements of tissues. Collagens form a superfamily of 28 trimeric proteins, distinguishable from the other ECM components by their particular abundance in tissues (collagens represent up to 80-90% of total proteins in skin, tendon and bones) and their capacity to self-assemble into supramolecular organized structures (the best known being the banded fibers). The collagen superfamily is highly complex and shows a remarkable diversity in structure, tissue distribution and function (Ricard-Blum and Ruggiero, 2005). The importance -
Blueprint Genetics Vitreoretinopathy Panel
Vitreoretinopathy Panel Test code: OP0701 Is a 24 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion / diagnosis of vitreoretinopathy. The genes on this panel are included in the Retinal Dystropy Panel. About Vitreoretinopathy Vitreoretinal diseases are characterised by the degeneration of the vitreous and retina of the eye. Several types of vitreoretinopathies exist giving rise to a spectrum of phenotypic presentations such as retinal detachment, optically empty vitreous, fibrillary condensation, cataract, and neovascularization. The condition includes familial exudative vitreoretinopathy, snowflake vitreoretinal degeneration, Norrie disease, Wagner syndrome, Stickler syndrome and Knobloch syndrome. The vitreoretinopathies may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. For instance, autosomal dominant familial exudative vitreoretinopathy (FEVR) is caused by mutations in FZD4; LRP5 has been associated with both autosomal dominant and recessive cases and NDP with X-linked FEVR. The clinical presentation and the disease course can be highly variable. The prevalence of FEVR is unknown, but it is a rare disorder. Availability 4 weeks Gene Set Description Genes in the Vitreoretinopathy Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ATOH7 Persistent hyperplastic primary vitreous, autosomal recessive AR 4 9 BEST1 Vitreoretinochoroidopathy, Microcornea, Rod-cone dystrophy, Posterior AD/AR 62 318 staphyloma, Bestrophinopathy,