caa a22 4500 397574673 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/hmg/5.5.607 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.5.607 cDNA Cloning of a Human Homologue of the Caenorhabditis Elegans Cell Fate-Determining Gene Mab-21: Expression, Chromosomal Localization and Analysis of a Highly Polymorphic (CAG)n Trinucleotide Repeat [Elektronische Daten] [Russell L. Margolis, O. Colin Stine, Melvin G. McInnis, Neal G. Ranen, David C. Rubinsztein, Jayne Leggo, Lorraine V. Jones Brando, Arif S. Kidwai, Scott J. Loev, Theresa S. Breschel, Colleen Callahan, Sylvia G. Simpson, J. Raymond DePaulo, Francis J. McMahon, Sanjeev Jain, Eugene S. Paykel, Cathy Walsh, Lynn E. DeLisi, Timothy J. Crow, E. Fuller Torrey, Roxann G. Ashworth, Jennifer P. Macke, Jeremy Nathans, Christopher A. Ross] The two most consistent features of the diseases caused by trinucleotide repeat expansion—neuropsychiatric symptoms and the phenomenon of genetic anticipation—may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identity and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of ∼3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5′-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13. © 1996 Oxford University Press Margolis Russell L. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Colin Stine O. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut McInnis Melvin G. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Ranen Neal G. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Rubinsztein David C. East Anglian Regional Genetics Service Molecular Genetics Laboratory, Cambridge CB2 2QQ, UK aut Leggo Jayne East Anglian Regional Genetics Service Molecular Genetics Laboratory, Cambridge CB2 2QQ, UK aut Jones Brando Lorraine V. Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Kidwai Arif S. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Loev Scott J. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Breschel Theresa S. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Callahan Colleen Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Simpson Sylvia G. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Raymond DePaulo J. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut McMahon Francis J. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Jain Sanjeev University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK aut Paykel Eugene S. University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK aut Walsh Cathy University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK aut DeLisi Lynn E. Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, New York, NY 11794-8101, USA aut Crow Timothy J. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK aut Fuller Torrey E. National Institute of Mental Health Neurosciences Center at St. Elizabeths, Washington, DC 20032, USA aut Ashworth Roxann G. Department of Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Macke Jennifer P. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Nathans Jeremy Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Ross Christopher A. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut Human Molecular Genetics Oxford University Press 5/5(1996-05), 607-616 0964-6906 5:5<607 1996 5 hmg https://doi.org/10.1093/hmg/5.5.607 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.5.607 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Margolis Russell L. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Colin Stine O. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- McInnis Melvin G. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Ranen Neal G. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Rubinsztein David C. East Anglian Regional Genetics Service Molecular Genetics Laboratory, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Leggo Jayne East Anglian Regional Genetics Service Molecular Genetics Laboratory, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Jones Brando Lorraine V. Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Kidwai Arif S. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Loev Scott J. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Breschel Theresa S. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Callahan Colleen Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Simpson Sylvia G. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Raymond DePaulo J. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- McMahon Francis J. Division of Psychiatric Genetics, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Jain Sanjeev University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Paykel Eugene S. University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- Walsh Cathy University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK aut NATIONALLICENCE 700 1- DeLisi Lynn E. Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, New York, NY 11794-8101, USA aut NATIONALLICENCE 700 1- Crow Timothy J. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK aut NATIONALLICENCE 700 1- Fuller Torrey E. National Institute of Mental Health Neurosciences Center at St. Elizabeths, Washington, DC 20032, USA aut NATIONALLICENCE 700 1- Ashworth Roxann G. Department of Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Macke Jennifer P. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Nathans Jeremy Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 700 1- Ross Christopher A. Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/5(1996-05), 607-616 0964-6906 5:5<607 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford