The Effect of Complement Factor H Y402H Polymorphism on Visual Outcomes After Anti
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Investigation of Modifier Genes Within Copy Number Variations in Rett Syndrome
See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/51147767 Investigation of modifier genes within copy number variations in Rett syndrome ARTICLE in JOURNAL OF HUMAN GENETICS · MAY 2011 Impact Factor: 2.53 · DOI: 10.1038/jhg.2011.50 · Source: PubMed CITATIONS DOWNLOADS VIEWS 6 89 134 15 AUTHORS, INCLUDING: Dag H Yasui Maria Antonietta Mencarelli University of California, Davis Azienda Ospedaliera Universitaria Senese 30 PUBLICATIONS 1,674 CITATIONS 58 PUBLICATIONS 962 CITATIONS SEE PROFILE SEE PROFILE Francesca Mari Janine M Lasalle Università degli Studi di Siena University of California, Davis 81 PUBLICATIONS 1,658 CITATIONS 98 PUBLICATIONS 3,525 CITATIONS SEE PROFILE SEE PROFILE Available from: Janine M Lasalle Retrieved on: 22 July 2015 Europe PMC Funders Group Author Manuscript J Hum Genet. Author manuscript; available in PMC 2012 January 01. Published in final edited form as: J Hum Genet. 2011 July ; 56(7): 508–515. doi:10.1038/jhg.2011.50. Europe PMC Funders Author Manuscripts Investigation of modifier genes within copy number variations in Rett syndrome Rosangela Artuso1,*, Filomena Tiziana Papa1,*, Elisa Grillo1, Mafalda Mucciolo1, Dag H. Yasui2, Keith W. Dunaway2, Vittoria Disciglio1, Maria Antonietta Mencarelli1, Marzia Pollazzon1, Michele Zappella3, Giuseppe Hayek4, Francesca Mari1, Alessandra Renieri1, Janine M. LaSalle2, and Francesca Ariani1 1 Medical Genetics Section, Biotechnology Department, University of Siena, Italy 2 Medical Microbiology and Immunology, Genome Center, School of Medicine, University of California, Davis, CA, USA 3 Child Neuropsychiatry, Versilia Hospital, Viareggio, Italy 4 Infantile Neuropsychiatry, Siena General Hospital, Italy Abstract MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). -
Complement Factor H Deficiency and Endocapillary Glomerulonephritis Due to Paternal Isodisomy and a Novel Factor H Mutation
Genes and Immunity (2011) 12, 90–99 & 2011 Macmillan Publishers Limited All rights reserved 1466-4879/11 www.nature.com/gene ORIGINAL ARTICLE Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation L Schejbel1, IM Schmidt2, M Kirchhoff3, CB Andersen4, HV Marquart1, P Zipfel5 and P Garred1 1Department of Clinical Immunology, Laboratory of Molecular Medicine, Rigshospitalet, Copenhagen, Denmark; 2Department of Pediatrics, Rigshospitalet, Copenhagen, Denmark; 3Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark; 4Department of Pathology, Rigshospitalet, Copenhagen, Denmark and 5Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany Complement factor H (CFH) is a regulator of the alternative complement activation pathway. Mutations in the CFH gene are associated with atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II and C3 glomerulonephritis. Here, we report a 6-month-old CFH-deficient child presenting with endocapillary glomerulonephritis rather than membranoproliferative glomerulonephritis (MPGN) or C3 glomerulonephritis. Sequence analyses showed homozygosity for a novel CFH missense mutation (Pro139Ser) associated with severely decreased CFH plasma concentration (o6%) but normal mRNA splicing and expression. The father was heterozygous carrier of the mutation, but the mother was a non-carrier. Thus, a large deletion in the maternal CFH locus or uniparental isodisomy was suspected. Polymorphic markers across chromosome 1 showed homozygosity for the paternal allele in all markers and a lack of the maternal allele in six informative markers. This combined with a comparative genomic hybridization assay demonstrated paternal isodisomy. Uniparental isodisomy increases the risk of homozygous variations in other genes on the affected chromosome. -
Gene Interaction of CFH, ARMS2, and ARMS2&Sol;HTRA1 on the Risk Of
Eye (2015) 29, 691–698 © 2015 Macmillan Publishers Limited All rights reserved 0950-222X/15 www.nature.com/eye 1,2,3,5 1,2,3,5 4,5 Gene–gene interaction L Huang , Q Meng , C Zhang , LABORATORY STUDY Y Sun1,2,3, Y Bai1,2,3,SLi1,2,3, X Deng1,2,3, of CFH, ARMS2, and B Wang1,2,3,WYu1,2,3, M Zhao1,2,3 and X Li1,2,3 ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population Abstract rs1065489 did not show significant association with nAMD (P40.01), but was strongly Purpose To evaluate the association and associated with PCV in Chinese patients 1Department of interaction of five single-nucleotide (Po0.001). Ophthalmology, Peking polymorphisms (SNPs) in three genes (CFH, University People’s Conclusions In this study, we found that the ARMS2, and ARMS2/HTRA1) with Hospital, Beijing, China interaction of ARMS2 and ARMS2/HTRA1 is neovascular age-related macular degeneration significantly associated with nAMD, and the 2 (nAMD) and polypoidal choroidal Key Laboratory of Vision interaction of CFH and ARMS2 is pronounced vasculopathy (PCV) in Chinese population. Loss and Restoration, in PCV development in Chinese population. Ministry of Education, Methods A total of 300 nAMD and 300 PCV Eye 29, – Beijing, China patients and 301 normal subjects participated (2015) 691 698; doi:10.1038/eye.2015.32; published online 13 March 2015 in the present study. The allelic variants of 3Department of Abdominal rs800292, rs2274700, rs3750847, rs3793917, and Surgical Oncology, Cancer rs1065489 were determined by matrix-assisted Institute and Hospital, Introduction laser desorption/ionization time-of-flight mass Chinese Academy of Medical Sciences, Peking – Age-related macular degeneration (AMD) is the spectrometry (MALDI-TOF-MS). -
Genetic Susceptibility to Age-Related Macular Degeneration: a Paradigm for Dissecting Complex Disease Traits
Human Molecular Genetics, 2007, Vol. 16, Review Issue 2 R174–R182 doi:10.1093/hmg/ddm212 Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits Anand Swaroop1,2,*, Kari EH Branham1, Wei Chen3 and Goncalo Abecasis3,* 1Departments of Ophthalmology and Visual Sciences, 2Department of Human Genetics and 3Department of Biostatistics, University of Michigan, Ann Arbor, MI 48105, USA Received July 20, 2007; Revised July 20, 2007; Accepted July 26, 2007 Age-related macular degeneration (AMD) is a progressive neurodegenerative disease, which affects quality of life for millions of elderly individuals worldwide. AMD is associated with a diverse spectrum of clinical phe- notypes, all of which include the death of photoreceptors in the central part of the human retina (called the macula). Tremendous progress has been made in identifying genetic susceptibility variants for AMD. Variants at chromosome 1q32 (in the region of CFH ) and 10q26 (LOC387715/ARMS2) account for a large part of the genetic risk to AMD and have been validated in numerous studies. In addition, susceptibility var- iants at other loci, several as yet unidentified, make substantial cumulative contribution to genetic risk for AMD; among these, multiple studies support the role of variants in APOE and C2/BF genes. Genome-wide association and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal relationships that connect genetic variants to AMD pathogenesis and should assist in better design of prevention and intervention. INTRODUCTION studies of AMD illustrate both the promise and challenges of new gene-mapping approaches. Early-onset maculopathies, A vast majority of common diseases are complex and such as Stargardt’s disease, have long been known to have her- multi-factorial, resulting from the interplay of genetic com- editary basis. -
(12) United States Patent (10) Patent No.: US 7,972,787 B2 Deangelis (45) Date of Patent: Jul
US007972 787B2 (12) United States Patent (10) Patent No.: US 7,972,787 B2 Deangelis (45) Date of Patent: Jul. 5, 2011 (54) METHODS FOR DETECTINGAGE-RELATED WO WO-2006088950 8, 2006 MACULAR DEGENERATION WO WO-2006133295 A2 12/2006 WO WO-2007044897 A1 4/2007 WO WO-2008O13893 A2 1, 2008 (75) Inventor: Margaret M. Deangelis, Cambridge, WO WO-2008067551 A2 6, 2008 MA (US) WO WO-2008094,370 A2 8, 2008 WO WO-2008103299 A2 8, 2008 WO WO-2008110828 A1 9, 2008 (73) Assignee: Massachusetts Eye and Ear Infirmary, WO WO-2008103299 A3 12/2008 Boston, MA (US) OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this Hirschhornet al. Genetics in Medicine. Mar. 2002. vol. 4. No. 2, pp. patent is extended or adjusted under 35 45-61 U.S.C. 154(b) by 391 days. Yang et all. Science. 2006. 314: 992-993 and supplemental online content. (21) Appl. No.: 12/032,154 GeneCard for the HTRA1 gene available via url: <genecards.org/cgi bin/carddisp.pl?gene=Htral D, printed Jul. 20, 2010.* Lucentini et al. The Scientist (2004) vol. 18, p. 20.* (22) Filed: Feb. 15, 2008 Wacholder et al. J. Natl. Cancer Institute (2004) 96(6);434-442.* Ioannidis et al. Nature genetics (2001) 29:306-309.* (65) Prior Publication Data Halushka et al. Nature. Ju1 1999. 22: 239-247. “HtrA1: A novel TGFB antagonist.” Development (2003) 131:502. US 2008/O2O6263 A1 Aug. 28, 2008 Adams et al. “HTRA1 Genotypes Associated with Risk of Neovascular Age-related Macular Degeneration Independent of CFH Related U.S. -
Population-Haplotype Models for Mapping and Tagging Structural Variation Using Whole Genome Sequencing
Population-haplotype models for mapping and tagging structural variation using whole genome sequencing Eleni Loizidou Submitted in part fulfilment of the requirements for the degree of Doctor of Philosophy Section of Genomics of Common Disease Department of Medicine Imperial College London, 2018 1 Declaration of originality I hereby declare that the thesis submitted for a Doctor of Philosophy degree is based on my own work. Proper referencing is given to the organisations/cohorts I collaborated with during the project. 2 Copyright Declaration The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives licence. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the licence terms of this work 3 Abstract The scientific interest in copy number variation (CNV) is rapidly increasing, mainly due to the evidence of phenotypic effects and its contribution to disease susceptibility. Single nucleotide polymorphisms (SNPs) which are abundant in the human genome have been widely investigated in genome-wide association studies (GWAS). Despite the notable genomic effects both CNVs and SNPs have, the correlation between them has been relatively understudied. In the past decade, next generation sequencing (NGS) has been the leading high-throughput technology for investigating CNVs and offers mapping at a high-quality resolution. We created a map of NGS-defined CNVs tagged by SNPs using the 1000 Genomes Project phase 3 (1000G) sequencing data to examine patterns between the two types of variation in protein-coding genes. -
A Hybrid CFHR3-1 Gene Causes Familial C3 Glomerulopathy
BRIEF COMMUNICATION www.jasn.org A Hybrid CFHR3-1 Gene Causes Familial C3 Glomerulopathy †‡ Talat H. Malik,* Peter J. Lavin, Elena Goicoechea de Jorge,* Katherine A. Vernon,* | Kirsten L. Rose,* Mitali P. Patel,* Marcel de Leeuw,§ John J. Neary, Peter J. Conlon,¶ † Michelle P. Winn, and Matthew C. Pickering* *Centre for Complement and Inflammation Research, Imperial College, London, United Kingdom; †Department of Medicine, Duke University Medical Center, Durham, North Carolina; ‡Trinity Health Kidney Centre, Tallaght Hospital, Trinity College, Dublin, Ireland; §Beckman Coulter Genomics, Grenoble, France; |Department of Renal Medicine, Royal Infirmary Edinburgh, Edinburgh, United Kingdom; and ¶Department of Nephrology, Beaumont Hospital, Dublin, Ireland ABSTRACT Controlled activation of the complement system, a key component of innate immunity, that CFHR1 and CFHR3 impair comple- enables destruction of pathogens with minimal damage to host tissue. Complement ment processing within the kidney. This factor H (CFH), which inhibits complement activation, and five CFH-related proteins hypothesis would predict that an increase (CFHR1–5) compose a family of structurally related molecules. Combined deletion of in CFHR1 and CFHR3 copy number would CFHR3 and CFHR1 is common and confers a protective effect in IgA nephropathy. Here, enhance susceptibility to complement- we report an autosomal dominant complement-mediated GN associated with abnormal mediated kidney injury. Here, we report increases in copy number across the CFHR3 and CFHR1 loci. In addition to normal a novel CFHR3–1 hybrid gene located on copies of these genes, affected individuals carry a unique hybrid CFHR3–1 gene. an allele that also contained intact copies In addition to identifying an association between these genetic observations and of the CFHR1 and CFHR3 genes. -
The Impact of Complement Genes on the Risk of Late-Onset Alzheimer's
G C A T T A C G G C A T genes Article The Impact of Complement Genes on the Risk of Late-Onset Alzheimer’s Disease Sarah M. Carpanini 1,2,† , Janet C. Harwood 3,† , Emily Baker 1, Megan Torvell 1,2, The GERAD1 Consortium ‡, Rebecca Sims 3 , Julie Williams 1 and B. Paul Morgan 1,2,* 1 UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK; [email protected] (S.M.C.); [email protected] (E.B.); [email protected] (M.T.); [email protected] (J.W.) 2 Division of Infection and Immunity, School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, CF14 4XN, UK 3 Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK; [email protected] (J.C.H.); [email protected] (R.S.) * Correspondence: [email protected] † These authors contributed equally to this work. ‡ Data used in the preparation of this article were obtained from the Genetic and Environmental Risk for Alzheimer’s disease (GERAD1) Consortium. As such, the investigators within the GERAD1 consortia contributed to the design and implementation of GERAD1 and/or provided data but did not participate in analysis or writing of this report. A full list of GERAD1 investigators and their affiliations is included in Supplementary File S1. Abstract: Late-onset Alzheimer’s disease (LOAD), the most common cause of dementia, and a huge global health challenge, is a neurodegenerative disease of uncertain aetiology. To deliver Citation: Carpanini, S.M.; Harwood, effective diagnostics and therapeutics, understanding the molecular basis of the disease is essential. -
Specific Correlation Between the Major Chromosome 10Q26 Haplotype Conferring Risk for Age-Related Macular Degeneration and the Expression of HTRA1
Molecular Vision 2017; 23:318-333 <http://www.molvis.org/molvis/v23/318> © 2017 Molecular Vision Received 5 December 2016 | Accepted 12 June 2017 | Published 14 June 2017 Specific correlation between the major chromosome 10q26 haplotype conferring risk for age-related macular degeneration and the expression of HTRA1 Sha-Mei Liao,1 Wei Zheng,1 Jiang Zhu,2 Casey A. Lewis,1 Omar Delgado,1 Maura A. Crowley,1 Natasha M. Buchanan,1 Bruce D. Jaffee,1 Thaddeus P. Dryja1 1Department of Ophthalmology; NIBR Informatics, Novartis Institutes for Biomedical Research, Cambridge, MA; 2Scientific Data Analysis, NIBR Informatics, Novartis Institutes for Biomedical Research, Cambridge, MA Purpose: A region within chromosome 10q26 has a set of single nucleotide polymorphisms (SNPs) that define a haplo- type that confers high risk for age-related macular degeneration (AMD). We used a bioinformatics approach to search for genes in this region that may be responsible for risk for AMD by assessing levels of gene expression in individuals carrying different haplotypes and by searching for open chromatin regions in the retinal pigment epithelium (RPE) that might include one or more of the SNPs. Methods: We surveyed the PubMed and the 1000 Genomes databases to find all common (minor allele frequency > 0.01) SNPs in 10q26 strongly associated with AMD. We used the HaploReg and LDlink databases to find sets of SNPs with alleles in linkage disequilibrium and used the Genotype-Tissue Expression (GTEx) database to search for correlations between genotypes at individual SNPs and the relative level of expression of the genes. We also accessed Encyclopedia of DNA Elements (ENCODE) to find segments of open chromatin in the region with the AMD-associated SNPs. -
Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch’S Membrane
Retinal Cell Biology Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch’s Membrane Ilene K. Sugino,1 Vamsi K. Gullapalli,1 Qian Sun,1 Jianqiu Wang,1 Celia F. Nunes,1 Noounanong Cheewatrakoolpong,1 Adam C. Johnson,1 Benjamin C. Degner,1 Jianyuan Hua,1 Tong Liu,2 Wei Chen,2 Hong Li,2 and Marco A. Zarbin1 PURPOSE. To determine whether resurfacing submacular human most, as cell survival is the worst on submacular Bruch’s Bruch’s membrane with a cell-deposited extracellular matrix membrane in these eyes. (Invest Ophthalmol Vis Sci. 2011;52: (ECM) improves retinal pigment epithelial (RPE) survival. 1345–1358) DOI:10.1167/iovs.10-6112 METHODS. Bovine corneal endothelial (BCE) cells were seeded onto the inner collagenous layer of submacular Bruch’s mem- brane explants of human donor eyes to allow ECM deposition. here is no fully effective therapy for the late complications of age-related macular degeneration (AMD), the leading Control explants from fellow eyes were cultured in medium T cause of blindness in the United States. The prevalence of only. The deposited ECM was exposed by removing BCE. Fetal AMD-associated choroidal new vessels (CNVs) and/or geo- RPE cells were then cultured on these explants for 1, 14, or 21 graphic atrophy (GA) in the U.S. population 40 years and older days. The explants were analyzed quantitatively by light micros- is estimated to be 1.47%, with 1.75 million citizens having copy and scanning electron microscopy. Surviving RPE cells from advanced AMD, approximately 100,000 of whom are African explants cultured for 21 days were harvested to compare bestro- American.1 The prevalence of AMD increases dramatically with phin and RPE65 mRNA expression. -
327341205.Pdf
CORE Metadata, citation and similar papers at core.ac.uk Provided by Newcastle University E-Prints Challis RC, Araujo GSR, Wong EKS, Anderson HE, Awan A, Dorman AM, Waldron M, Wilson V, Brocklebank V, Strain L, Morgan BP, Harris CL, Marchbank KJ, Goodship THJ, Kavanagh D. A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic Syndrome. Journal of the American Society of Nephrology 2015, 27(6), 1617-1624. Copyright: This is the authors’ accepted manuscript of an article that has been published in its final definitive form by the American Society of Nephrology, 2015. DOI link to article: http://dx.doi.org/10.1681/ASN.2015010100 Date deposited: 05/10/2015 Embargo release date: 01 June 2017 Newcastle University ePrints - eprint.ncl.ac.uk CFH/CFHR3 hybrid gene in aHUS A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic Syndrome Rachel C. Challis1*, Geisilaine S.R. Araujo1*, Edwin K.S. Wong1*, Holly E. Anderson1, Atif Awan2, Anthony M. Dorman3, Mary Waldron2, Valerie Wilson1, Vicky Brocklebank1, Lisa Strain1, B. Paul Morgan4, Claire L. Harris4, Kevin J. Marchbank5, Timothy H.J. Goodship1, David Kavanagh1 1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne. 2Department of Nephrology, Children’s University Hospital, Dublin, Ireland. 3Beaumont Hospital and RCSI, Dublin, Ireland. 4 Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom. 5Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne. -
And Non-Risk-Associated Variants at the 10Q26 AMD Locus Influence ARMS2 Mrna Expression but Exclude Pathogenic Effects Due to Protein Deficiency
Human Molecular Genetics, 2011, Vol. 20, No. 7 1387–1399 doi:10.1093/hmg/ddr020 Advance Access published on January 20, 2011 Risk- and non-risk-associated variants at the 10q26 AMD locus influence ARMS2 mRNA expression but exclude pathogenic effects due to protein deficiency Ulrike Friedrich1, Connie A. Myers2, Lars G. Fritsche1, Andrea Milenkovich1, Armin Wolf3, Joseph C. Corbo 2 and Bernhard H.F. Weber1,∗ 1Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany, 2Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA and 3Department of Ophthalmology, Ludwig-Maximilians University, Mathildenstrasse 8, 80336 Munich, Germany Received December 11, 2010; Revised and Accepted January 13, 2011 Fifteen variants in 10q26 are in strong linkage disequilibrium and are associated with an increased risk for age-related macular degeneration (AMD), a frequent cause of blindness in developed countries. These var- iants tag a single-risk haplotype encompassing the genes ARMS2 (age-related maculopathy susceptibility 2) and part of HTRA1 (HtrA serine peptidase 1). To define the true AMD susceptibility gene in 10q26, several studies have focused on the influence of risk alleles on the expression of ARMS2 and/or HTRA1,butthe results have been inconsistent. By heterologous expression of genomic ARMS2 variants, we now show that ARMS2 mRNA levels transcribed from the risk haplotype are significantly reduced compared with non-risk mRNA isoforms. Analyzing variant ARMS2 constructs, this effect could specifically be assigned to the known insertion/deletion polymorphism (c.(∗)372_815del443ins54) in the 3′-untranslated region of ARMS2.