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18 results on '"Korvatska, E"'

1. Mutation hot spots in the 5p31-linked corneal dystrophies

Author

Korvatska, E., Munier, F.L., Djemai, A., Wang, M.X., Frueh, B., Chiou, A. G.Y., Uffer, S., Ballestrazzi, E., Braunstein, R.E., Forster, R.K., Culbertson, W.W., Boman, H., Zografos, L., and Schorderet, D.F.

Subjects
Gene mutations -- Physiological aspects, Corneal diseases -- Genetic aspects, Blindness -- Causes of, Biological sciences
Abstract

Mutations in the BIGH3 gene on chromosome 5q31 cause 4 distinct autosomal dominant human cornea diseases characterized by accumulation of corneal deposits in a progressive fashion and in time by loss of vision. A specific recurrent missense mutation for each type of dystrophy is in 10 independently ascertained families. Genotype analysis with microsatellite markers around BIGH3 has been carried out for the 10 families and in 5 families reported in the past. New data imply that R555W, H124H and R124C mutations were independent in a number of ethnic groups. Apparently the mutations don't reflect a putative founder effect. The specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5p has been confirmed.

Published
1998

2. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author

Szatmari, P, Paterson, AD, Zwaigenbaum, L, Roberts, W, Brian, J, Liu, XQ, Vincent, JB, Skaug, JL, Thompson, AP, Senman, L, Feuk, L, Qian, C, Bryson, SE, Jones, MB, Marshall, CR, Scherer, SW, Vieland, VJ, Bartlett, C, Mangin, LV, Goedken, R, Segre, A, Pericak-Vance, MA, Cuccaro, ML, Gilbert, JR, Wright, HH, Abramson, RK, Betancur, C, Bourgeron, T, Gillberg, C, Leboyer, M, Buxbaum, JD, Davis, KL, Hollander, E, Silverman, JM, Hallmayer, J, Lotspeich, L, Sutcliffe, JS, Haines, JL, Folstein, SE, Piven, J, Wassink, TH, Sheffield, V, Geschwind, DH, Bucan, M, Brown, WT, Cantor, RM, Constantino, JN, Gilliam, TC, Herbert, M, LaJonchere, C, Ledbetter, DH, Lese-Martin, C, Miller, J, Nelson, S, Samango-Sprouse, CA, Spence, S, State, M, Tanzi, RE, Coon, H, Dawson, G, Devlin, B, Estes, A, Flodman, P, Klei, L, McMahon, WM, Minshew, N, Munson, J, Korvatska, E, Rodier, PM, Schellenberg, GD, Smith, M, Spence, MA, Stodgell, C, Tepper, PG, Wijsman, EM, Yu, CE, Rogé, B, Mantoulan, C, Wittemeyer, K, Poustka, A, Felder, B, Klauck, SM, Schuster, C, Poustka, F, Bölte, S, Feineis-Matthews, S, Herbrecht, E, Schmötzer, G, Tsiantis, J, Papanikolaou, K, Maestrini, E, and Bacchelli, E

Subjects
mental disorders
Abstract

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs. © 2007 Nature Publishing Group.

Published
2007

3. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author

Szatmari, P. Paterson, A.D. Zwaigenbaum, L. Roberts, W. Brian, J. Liu, X.-Q. Vincent, J.B. Skaug, J.L. Thompson, A.P. Senman, L. Feuk, L. Qian, C. Bryson, S.E. Jones, M.B. Marshall, C.R. Scherer, S.W. Vieland, V.J. Bartlett, C. Mangin, L.V. Goedken, R. Segre, A. Pericak-Vance, M.A. Cuccaro, M.L. Gilbert, J.R. Wright, H.H. Abramson, R.K. Betancur, C. Bourgeron, T. Gillberg, C. Leboyer, M. Buxbaum, J.D. Davis, K.L. Hollander, E. Silverman, J.M. Hallmayer, J. Lotspeich, L. Sutcliffe, J.S. Haines, J.L. Folstein, S.E. Piven, J. Wassink, T.H. Sheffield, V. Geschwind, D.H. Bucan, M. Brown, W.T. Cantor, R.M. Constantino, J.N. Gilliam, T.C. Herbert, M. LaJonchere, C. Ledbetter, D.H. Lese-Martin, C. Miller, J. Nelson, S. Samango-Sprouse, C.A. Spence, S. State, M. Tanzi, R.E. Coon, H. Dawson, G. Devlin, B. Estes, A. Flodman, P. Klei, L. McMahon, W.M. Minshew, N. Munson, J. Korvatska, E. Rodier, P.M. Schellenberg, G.D. Smith, M. Spence, M.A. Stodgell, C. Tepper, P.G. Wijsman, E.M. Yu, C.-E. Rogé, B. Mantoulan, C. Wittemeyer, K. Poustka, A. Felder, B. Klauck, S.M. Schuster, C. Poustka, F. Bölte, S. Feineis-Matthews, S. Herbrecht, E. Schmötzer, G. Tsiantis, J. Papanikolaou, K. Maestrini, E. Bacchelli, E. Blasi, F. Carone, S. Toma, C. Van Engeland, H. De Jonge, M. Kemner, C. Koop, F. Langemeijer, M. Hijimans, C. Staal, W.G. Baird, G. Bolton, P.F. Rutter, M.L. Weisblatt, E. Green, J. Aldred, C. Wilkinson, J.-A. Pickles, A. Le Couteur, A. Berney, T. McConachie, H. Bailey, A.J. Francis, K. Honeyman, G. Hutchinson, A. Parr, J.R. Wallace, S. Monaco, A.P. Barnby, G. Kobayashi, K. Lamb, J.A. Sousa, I. Sykes, N. Cook, E.H. Guter, S.J. Leventhal, B.L. Salt, J. Lord, C. Corsello, C. Hus, V. Weeks, D.E. Volkmar, F. Tauber, M. Fombonne, E. Shih, A.

Subjects
mental disorders
Abstract

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs. © 2007 Nature Publishing Group.

Published
2007

5. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice

Author

Melrose, H.L., primary, Dächsel, J.C., additional, Behrouz, B., additional, Lincoln, S.J., additional, Yue, M., additional, Hinkle, K.M., additional, Kent, C.B., additional, Korvatska, E., additional, Taylor, J.P., additional, Witten, L., additional, Liang, Y.-Q., additional, Beevers, J.E., additional, Boules, M., additional, Dugger, B.N., additional, Serna, V.A., additional, Gaukhman, A., additional, Yu, X., additional, Castanedes-Casey, M., additional, Braithwaite, A.T., additional, Ogholikhan, S., additional, Yu, N., additional, Bass, D., additional, Tyndall, G., additional, Schellenberg, G.D., additional, Dickson, D.W., additional, Janus, C., additional, and Farrer, M.J., additional

Published
2010
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6. Mutation Hot Spots in 5q31-Linked Corneal Dystrophies

Author

Korvatska, E., primary, Munier, F.L., additional, Djemaï, A., additional, Wang, M.X., additional, Frueh, B., additional, Chiou, A.G.-Y., additional, Uffer, S., additional, Ballestrazzi, E., additional, Braunstein, R.E., additional, Forster, R.K., additional, Culbertson, W.W., additional, Boman, H., additional, Zografos, L., additional, and Schorderet, D.F., additional

Published
1998
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8. Amyloid and non-amyloid forms of 5q31-linked corneal dystrophy resulting from kerato-epithelin mutations at Arg-124 are associated with abnormal turnover of the protein.

Author

Korvatska, E, Henry, H, Mashima, Y, Yamada, M, Bachmann, C, Munier, F L, and Schorderet, D F

Abstract

Mutations in kerato-epithelin are responsible for a group of hereditary cornea-specific deposition diseases, 5q31-linked corneal dystrophies. These conditions are characterized by progressive accumulation of protein deposits of different ultrastructure. Herein, we studied the corneas with mutations at kerato-epithelin residue Arg-124 resulting in amyloid (R124C), non-amyloid (R124L), and a mixed pattern of deposition (R124H). We found that aggregated kerato-epithelin comprised all types of pathological deposits. Each mutation was associated with characteristic changes of protein turnover in corneal tissue. Amyloidogenesis in R124C corneas was accompanied by the accumulation of N-terminal kerato-epithelin fragments, whereby species of 44 kDa were the major constituents of amyloid fibrils. R124H corneas with prevailing non-amyloid inclusions showed accumulation of a new 66-kDa species altogether with the full-size 68-kDa form. Finally, in R124L cornea with non amyloid deposits, we found only the accumulation of the 68-kDa form. Two-dimensional gels revealed mutation-specific changes in the processing of the full-size protein in all affected corneas. It appears that substitutions at the same residue (Arg-124) result in cornea-specific deposition of kerato-epithelin via distinct aggregation pathways each involving altered turnover of the protein in corneal tissue.

Published
2000

9. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author

Peter, Szatmari, Andrew D, Paterson, Lonnie, Zwaigenbaum, Wendy, Roberts, Jessica, Brian, Xiao-Qing, Liu, John B, Vincent, Jennifer L, Skaug, Ann P, Thompson, Lili, Senman, Lars, Feuk, Cheng, Qian, Susan E, Bryson, Marshall B, Jones, Christian R, Marshall, Stephen W, Scherer, Veronica J, Vieland, Christopher, Bartlett, La Vonne, Mangin, Rhinda, Goedken, Alberto, Segre, Margaret A, Pericak-Vance, Michael L, Cuccaro, John R, Gilbert, Harry H, Wright, Ruth K, Abramson, Catalina, Betancur, Thomas, Bourgeron, Christopher, Gillberg, Marion, Leboyer, Joseph D, Buxbaum, Kenneth L, Davis, Eric, Hollander, Jeremy M, Silverman, Joachim, Hallmayer, Linda, Lotspeich, James S, Sutcliffe, Jonathan L, Haines, Susan E, Folstein, Joseph, Piven, Thomas H, Wassink, Val, Sheffield, Daniel H, Geschwind, Maja, Bucan, W Ted, Brown, Rita M, Cantor, John N, Constantino, T Conrad, Gilliam, Martha, Herbert, Clara, Lajonchere, David H, Ledbetter, Christa, Lese-Martin, Janet, Miller, Stan, Nelson, Carol A, Samango-Sprouse, Sarah, Spence, Matthew, State, Rudolph E, Tanzi, Hilary, Coon, Geraldine, Dawson, Bernie, Devlin, Annette, Estes, Pamela, Flodman, Lambertus, Klei, William M, McMahon, Nancy, Minshew, Jeff, Munson, Elena, Korvatska, Patricia M, Rodier, Gerard D, Schellenberg, Moyra, Smith, M Anne, Spence, Chris, Stodgell, Ping Guo, Tepper, Ellen M, Wijsman, Chang-En, Yu, Bernadette, Rogé, Carine, Mantoulan, Kerstin, Wittemeyer, Annemarie, Poustka, Bärbel, Felder, Sabine M, Klauck, Claudia, Schuster, Fritz, Poustka, Sven, Bölte, Sabine, Feineis-Matthews, Evelyn, Herbrecht, Gabi, Schmötzer, John, Tsiantis, Katerina, Papanikolaou, Elena, Maestrini, Elena, Bacchelli, Francesca, Blasi, Simona, Carone, Claudio, Toma, Herman, Van Engeland, Maretha, de Jonge, Chantal, Kemner, Frederieke, Koop, Frederike, Koop, Marjolein, Langemeijer, Marjolijn, Langemeijer, Channa, Hijmans, Channa, Hijimans, Wouter G, Staal, Gillian, Baird, Patrick F, Bolton, Michael L, Rutter, Emma, Weisblatt, Jonathan, Green, Catherine, Aldred, Julie-Anne, Wilkinson, Andrew, Pickles, Ann, Le Couteur, Tom, Berney, Helen, McConachie, Anthony J, Bailey, Kostas, Francis, Gemma, Honeyman, Aislinn, Hutchinson, Jeremy R, Parr, Simon, Wallace, Anthony P, Monaco, Gabrielle, Barnby, Kazuhiro, Kobayashi, Janine A, Lamb, Ines, Sousa, Nuala, Sykes, Edwin H, Cook, Stephen J, Guter, Bennett L, Leventhal, Jeff, Salt, Catherine, Lord, Christina, Corsello, Vanessa, Hus, Daniel E, Weeks, Fred, Volkmar, Maïté, Tauber, Eric, Fombonne, Andy, Shih, Kacie J, Meyer, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Centre for Applied Genomics, Toronto, University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Department of Pediatrics, University of Alberta, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Department of Psychiatry, University of Toronto, Departments of Pediatrics and Psychology, Dalhousie University [Halifax], Department of Neural and Behavioral Sciences, Pennsylvania State University (Penn State), Penn State System-Penn State System, Department of Molecular Genetics [Toronto], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Department of Pathology and Laboratory Medicine, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Computer Science, University of Iowa [Iowa City], John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], W.S. Hall Psychiatric Institute, University of South Carolina [Columbia], Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Institute of Child Health, University College of London [London] (UCL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Neuroscience, PennState Meteorology Department, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Psychiatry and Behavioral Sciences [Stanford], Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Johns Hopkins University (JHU), Carolina Institute for Developmental Disabilities, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Department of Neurology, UCLA School of Medicine, Department of Genetics, University of Pennsylvania [Philadelphia]-School of Medicine, N.Y.S. Institute for Basic Research in Developmental Disabilities, Department of Human Genetics, UCLA, University of California [Los Angeles] (UCLA), University of California-University of California-Semel Institute, Washington University in Saint Louis (WUSTL), University of Chicago, Harvard Medical School [Boston] (HMS), Autism Genetic Resource Exchange, Autism Speaks, Emory University [Atlanta, GA], Developmental Brain and Behaviour Unit, University of Southampton, Cure Autism Now, Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Children's National Medical Center, The George Washington University (GW), Massachusetts General Hospital, Massachusetts General Hospital [Boston], Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Autism Speaks and the Department of Psychiatry, Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], University of California [Irvine] (UCI), University of California-University of California, Department of Psychiatry and Behavioral Sciences, Department of OB/GYN, University of Rochester Medical Center, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Department of Epidemiology, University of Pittsburgh (PITT), Departments of Biostatistics and Medicine, Department of Medicine, Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Centre de Référence du Syndrome de Prader-Willi, CHU Toulouse [Toulouse], University of Oxford [Oxford]-Warneford Hospital, Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Medical Genetics Laboratory, Policlinico S. Orsola-Malpighi, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Department of Neurocognition, Maastricht University [Maastricht], Newcomen Centre, Guy's Hospital [London], Department of Child and Adolescent Psychiatry, Institute of psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, University of Cambridge Clinical School, University of Cambridge [UK] (CAM), Manchester Academic Health Sciences Centre, Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), Child and Adolescent Mental Health, Newcastle University [Newcastle], Institutes of Neuroscience and Health and Society, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Institute for Juvenile Research, University of Illinois [Chicago] (UIC), Department of Disability and Human Development, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Human Genetics Department, SFU Discrete Mathematics Group (SFU-DMG), Simon Fraser University (SFU.ca), Child Study Centre, Yale University School of Medicine, Centre d'Endocrinologie, Maladies Osseuses, Génétique et Gynécologie Médicale, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), Scientific Affairs, Autism Genome Project Consortium, RS: FPN CN II, Cognitive Neuroscience, MUMC+: HZC Klinische Neurofysiologie (5), The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, University of California (UC)-University of California (UC)-Semel Institute, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), King‘s College London-The Institute of Psychiatry, Yale School of Medicine [New Haven, Connecticut] (YSM), Betancur, Catalina, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-School of Medicine, University of Pennsylvania, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Oxford-Warneford Hospital, University of Oxford, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT), Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, Vincent JB, Skaug JL, Thompson AP, Senman L, Feuk L, Qian C, Bryson SE, Jones MB, Marshall CR, Scherer SW, Vieland VJ, Bartlett C, Mangin LV, Goedken R, Segre A, Pericak-Vance MA, Cuccaro ML, Gilbert JR, Wright HH, Abramson RK, Betancur C, Bourgeron T, Gillberg C, Leboyer M, Buxbaum JD, Davis KL, Hollander E, Silverman JM, Hallmayer J, Lotspeich L, Sutcliffe JS, Haines JL, Folstein SE, Piven J, Wassink TH, Sheffield V, Geschwind DH, Bucan M, Brown WT, Cantor RM, Constantino JN, Gilliam TC, Herbert M, Lajonchere C, Ledbetter DH, Lese-Martin C, Miller J, Nelson S, Samango-Sprouse CA, Spence S, State M, Tanzi RE, Coon H, Dawson G, Devlin B, Estes A, Flodman P, Klei L, McMahon WM, Minshew N, Munson J, Korvatska E, Rodier PM, Schellenberg GD, Smith M, Spence MA, Stodgell C, Tepper PG, Wijsman EM, Yu CE, Roge B, Mantoulan C, Wittemeyer K, Poustka A, Felder B, Klauck SM, Schuster C, Poustka F, Bolte S, Feineis-Matthews S, Herbrecht E, Schmotzer G, Tsiantis J, Papanikolaou K, Maestrini E, Bacchelli E, Blasi F, Carone S, Toma C, Van Engeland H, de Jonge M, Kemner C, Koop F, Langemeijer M, Hijimans C, Staal WG, Baird G, Bolton PF, Rutter ML, Weisblatt E, Green J, Aldred C, Wilkinson JA, Pickles A, Le Couteur A, Berney T, McConachie H, Bailey AJ, Francis K, Honeyman G, Hutchinson A, Parr JR, Wallace S, Monaco AP, Barnby G, Kobayashi K, Lamb JA, Sousa I, Sykes N, Cook EH, Guter SJ, Leventhal BL, Salt J, Lord C, Corsello C, Hus V, Weeks DE, Volkmar F, Tauber M, Fombonne E, and Shih A.

Subjects
Male, genetic structures, Genetic Linkage, Neurexin, [SDV.GEN] Life Sciences [q-bio]/Genetics, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Heritability of autism, Copy-number variation, MESH: Genetic Variation, Genetics, 0303 health sciences, medicine.diagnostic_test, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, Chromosome Mapping, 3. Good health, Female, MESH: Genetic Linkage, MESH: Autistic Disorder, Epigenetics of autism, Biology, Article, 03 medical and health sciences, Genetic linkage, mental disorders, medicine, Humans, MESH: Chromosome Aberrations, Family, Genetic Predisposition to Disease, Genetic Testing, Autistic Disorder, MESH: Family, 030304 developmental biology, Genetic testing, Chromosome Aberrations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Genetic Variation, medicine.disease, Genetic architecture, MESH: Male, MESH: Lod Score, Autism, Lod Score, MESH: Chromosome Mapping, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Published
2007

10. Tau isoform regulation is region- and cell-specific in mouse brain.

Author

McMillan P, Korvatska E, Poorkaj P, Evstafjeva Z, Robinson L, Greenup L, Leverenz J, Schellenberg GD, and D'Souza I

Subjects
Aging metabolism, Animals, Animals, Newborn, Brain cytology, Exons genetics, Frontal Lobe cytology, Frontal Lobe growth & development, Frontal Lobe metabolism, Gene Expression Regulation, Developmental genetics, Hippocampus cytology, Hippocampus growth & development, Hippocampus metabolism, Humans, Mice, Mice, Transgenic, Phosphorylation, Protein Isoforms genetics, Protein Isoforms metabolism, Species Specificity, Synaptic Membranes metabolism, Synaptic Membranes ultrastructure, tau Proteins genetics, Brain growth & development, Brain metabolism, Neurons metabolism, tau Proteins metabolism
Abstract

Tau is a microtubule-associated protein implicated in neurodegenerative tauopathies. Alternative splicing of the tau gene (MAPT) generates six tau isoforms, distinguishable by the exclusion or inclusion of a repeat region of exon 10, which are referred to as 3-repeat (3R) and 4-repeat (4R) tau, respectively. We developed transgenic mouse models that express the entire human MAPT gene in the presence and absence of the mouse Mapt gene and compared the expression and regulation of mouse and human tau isoforms during development and in the young adult. We found differences between mouse and human tau in the regulation of exon 10 inclusion. Despite these differences, the isoform splicing pattern seen in normal human brain is replicated in our mouse models. In addition, we found that all tau, both in the neonate and young adult, is phosphorylated. We also examined the normal anatomic distribution of mouse and human tau isoforms in mouse brain. We observed developmental and species-specific variations in the expression of 3R- and 4R-tau within the frontal cortex and hippocampus. In addition, there were differences in the cellular distribution of the isoforms. Mice transgenic for the human MAPT gene exhibited higher levels of neuronal cell body expression of tau compared to wildtype mice. This neuronal cell body expression of tau was limited to the 3R isoform, whereas expression of 4R-tau was more "synaptic like," with granular staining of neuropil rather than in neuronal cell bodies. These developmental and species-specific differences in the regulation and distribution of tau isoforms may be important to the understanding of normal and pathologic tau isoform expression.

Published
2008
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11. Heterogeneous association between engrailed-2 and autism in the CPEA network.

Author

Brune CW, Korvatska E, Allen-Brady K, Cook EH Jr, Dawson G, Devlin B, Estes A, Hennelly M, Hyman SL, McMahon WM, Munson J, Rodier PM, Schellenberg GD, Stodgell CJ, and Coon H

Subjects
Family, Genotype, Humans, Language Development, Linkage Disequilibrium, Pedigree, Phenotype, Autistic Disorder genetics, Genetic Heterogeneity, Genetic Predisposition to Disease, Homeodomain Proteins genetics, Nerve Tissue Proteins genetics
Abstract

Autism is a neurodevelopmental disorder characterized by an early onset of abnormal social, communicative, and repetitive behavior. Engrailed-2 (EN2) was identified as an autism candidate gene because its influence on cerebellar development in mice parallels neurodevelopmental abnormalities seen in individuals with autism. Studies investigating association between markers at EN2 (chr7q36), a location associated with language disorders, and autism reveal mixed findings. Two positive reports revealed association with two intronic SNPs. Since the associated SNPs were in high linkage disequilibrium and shared similar minor allele frequencies, we chose to test whether one of the SNPs (rs1861972) was associated with autism in three recruiting sites from the NIH Collaborative Programs of Excellence in Autism (CPEA) network. A recessive model revealed significant association with broad autism spectrum disorder. Site specific analyses indicated differential allele transmission by site, despite similar ethnicity, and parental genotypes, suggesting the SNP may contribute to various risk haplotypes. No significant association with autism was found under an additive model for either a broad (autism spectrum disorder) or a narrow (autistic disorder) diagnostic group. Although our findings were not as robust as the previous studies, they suggest that rs1861972 may influence the risk for autism spectrum disorders. Future studies investigating EN2 should consider how the association of variants in this gene with autism could be influenced by differences in phenotype and possible interactions with genotypes at other autism candidate genes.

Published
2008
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12. Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

Author

Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, Vincent JB, Skaug JL, Thompson AP, Senman L, Feuk L, Qian C, Bryson SE, Jones MB, Marshall CR, Scherer SW, Vieland VJ, Bartlett C, Mangin LV, Goedken R, Segre A, Pericak-Vance MA, Cuccaro ML, Gilbert JR, Wright HH, Abramson RK, Betancur C, Bourgeron T, Gillberg C, Leboyer M, Buxbaum JD, Davis KL, Hollander E, Silverman JM, Hallmayer J, Lotspeich L, Sutcliffe JS, Haines JL, Folstein SE, Piven J, Wassink TH, Sheffield V, Geschwind DH, Bucan M, Brown WT, Cantor RM, Constantino JN, Gilliam TC, Herbert M, Lajonchere C, Ledbetter DH, Lese-Martin C, Miller J, Nelson S, Samango-Sprouse CA, Spence S, State M, Tanzi RE, Coon H, Dawson G, Devlin B, Estes A, Flodman P, Klei L, McMahon WM, Minshew N, Munson J, Korvatska E, Rodier PM, Schellenberg GD, Smith M, Spence MA, Stodgell C, Tepper PG, Wijsman EM, Yu CE, Rogé B, Mantoulan C, Wittemeyer K, Poustka A, Felder B, Klauck SM, Schuster C, Poustka F, Bölte S, Feineis-Matthews S, Herbrecht E, Schmötzer G, Tsiantis J, Papanikolaou K, Maestrini E, Bacchelli E, Blasi F, Carone S, Toma C, Van Engeland H, de Jonge M, Kemner C, Koop F, Langemeijer M, Hijmans C, Staal WG, Baird G, Bolton PF, Rutter ML, Weisblatt E, Green J, Aldred C, Wilkinson JA, Pickles A, Le Couteur A, Berney T, McConachie H, Bailey AJ, Francis K, Honeyman G, Hutchinson A, Parr JR, Wallace S, Monaco AP, Barnby G, Kobayashi K, Lamb JA, Sousa I, Sykes N, Cook EH, Guter SJ, Leventhal BL, Salt J, Lord C, Corsello C, Hus V, Weeks DE, Volkmar F, Tauber M, Fombonne E, Shih A, and Meyer KJ

Subjects
Autistic Disorder diagnosis, Family, Female, Genetic Variation, Humans, Lod Score, Male, Risk Factors, Autistic Disorder genetics, Chromosome Aberrations, Chromosome Mapping, Genetic Linkage, Genetic Predisposition to Disease, Genetic Testing methods
Abstract

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Published
2007
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13. Genetic and immunologic considerations in autism.

Author

Korvatska E, Van de Water J, Anders TF, and Gershwin ME

Subjects
Autistic Disorder virology, Genetic Predisposition to Disease, Humans, Neuroimmunomodulation, Autistic Disorder genetics, Autistic Disorder immunology
Abstract

According to recent epidemiological surveys, autistic spectrum disorders have become recognized as common childhood psychopathologies. These life-lasting conditions demonstrate a strong genetic determinant consistent with a polygenic mode of inheritance for which several autism susceptibility regions have been identified. Parallel evidence of immune abnormalities in autistic patients argues for an implication of the immune system in pathogenesis. This review summarizes advances in the molecular genetics of autism, as well as recently emerging concerns addressing the disease incidence and triggering factors. The neurochemical and immunologic findings are analyzed in the context of a neuroimmune hypothesis for autism. Studies of disorders with established neuroimmune nature indicate multiple pathways of the pathogenesis; herein, we discuss evidence of similar phenomena in autism., ((c)2002 Elsevier Science (USA).)

Published
2002
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14. Haplotye analysis of Jaanese families with a superficial variant of granular corneal dystrohy: evidence for multiple origins of R124L mutation of keratoepithelin.

Author

Korvatska E, Yamada M, Yamamoto S, Okada M, Munier FL, Schorderet DF, and Mashima Y

Subjects
Female, Humans, Japan, Male, Pedigree, Asian People genetics, Corneal Dystrophies, Hereditary genetics, Extracellular Matrix Proteins, Genetic Variation, Haplotypes, Mutation, Neoplasm Proteins genetics, Transforming Growth Factor beta
Published
2000

15. On the role of kerato-epithelin in the pathogenesis of 5q31-linked corneal dystrophies.

Author

Korvatska E, Munier FL, Chaubert P, Wang MX, Mashima Y, Yamada M, Uffer S, Zografos L, and Schorderet DF

Subjects
Amyloid metabolism, Animals, Blotting, Western, Cells, Cultured, Cornea metabolism, Corneal Dystrophies, Hereditary metabolism, Corneal Dystrophies, Hereditary pathology, Corneal Dystrophies, Hereditary surgery, DNA Primers chemistry, Fibroblasts metabolism, Humans, Immunoenzyme Techniques, Keratoplasty, Penetrating, Mutation, Missense, Peptide Fragments, Rabbits, Chromosomes, Human, Pair 5, Corneal Dystrophies, Hereditary etiology, Extracellular Matrix Proteins, Genetic Linkage, Neoplasm Proteins physiology, Transforming Growth Factor beta physiology
Abstract

Purpose: Recently, the authors identified a gene, BIGH3, in which different mutations cause a group of hereditary corneal dystrophies: lattice type I and IIIA (CDLI and CDLIIIA), granular Groenouw type I (CDGGI), Avellino (CDA), and Reis-Bücklers' (CDRB). All these disorders are characterized by the progressive accumulation of corneal deposits with different structural organization. Experiments were conducted to determine the role of kerato-epithelin (KE), the product of BIGH3, in the pathogenesis of the diseases., Methods: KE-15 and KE-2, two rabbit antisera raised against peptides from the 69-364 and 426 - 682 amino acid regions of KE respectively, were used for immunohistology of the corneas obtained after keratoplasty in six CDLI patients, three CDGGI patients, and one CDA patient., Results: The nonamyloid deposits observed in CDGGI stained intensively with KE-15 and KE-2, whereas the amyloid deposits in all analyzed CDLI corneas reacted to KE-2 but not to KE-15. In the CDA cornea, where amyloid and nonamyloid inclusions were present, positive staining with both antisera was observed., Conclusions: Pathologic amyloid and nonamyloid deposits observed in CDLI, CDGGI-, and CDA-affected corneas are caused by KE accumulation. Different staining patterns of amyloid and nonamyloid deposits observed with antibodies against the amino and carboxyl termini of KE suggest that two mechanisms of KE misfolding are implicated in the pathogenesis of 5q31-linked corneal dystrophies.

Published
1999

16. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies.

Author

Munier FL, Korvatska E, Djemaï A, Le Paslier D, Zografos L, Pescia G, and Schorderet DF

Subjects
Alternative Splicing, Base Sequence, Cells, Cultured, Chromosome Mapping, Chromosomes, Artificial, Yeast, Cornea metabolism, DNA Primers, Dinucleoside Phosphates, Exons, Genes, Dominant, Genetic Linkage, Humans, Introns, Molecular Sequence Data, Polymerase Chain Reaction, Skin metabolism, Chromosomes, Human, Pair 5, Corneal Dystrophies, Hereditary genetics, Extracellular Matrix Proteins, Neoplasm Proteins genetics, Point Mutation, Transforming Growth Factor beta
Abstract

Granular dystrophy Groenouw type I (CDGG1), Reis-Bücklers (CDRB), lattice type I (CDL1) and Avellino (ACD) are four 5q31-linked human autosomal dominant corneal dystrophies. Clinically, they show progressive opacification of the cornea leading to severe visual handicap. The nature of the deposits remains unknown in spite of amyloid aetiology ascribed to the last two. We generated a YAC contig of the linked region and, following cDNA selection, recovered the beta ig-h3 gene. In six affected families we identified missense mutations. All detected mutations occurred at the CpG dinucleotide of two arginine codons: R555W in one CDGG1, R555Q in one CDRB, R124C in two CDL1 and R124H in two ACD families. This suggests, as the last two diseases are characterized by amyloid deposits, that R124 mutated kerato-epithelin (the product of beta ig-h3) forms amyloidogenic intermediates that precipitate in the cornea. Our data establish a common molecular origin for the 5q31-linked corneal dystrophies.

Published
1997
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17. Delineation of a 1-cM region on distal 5q containing the locus for corneal dystrophies Groenouw type I and lattice type I and exclusion of the candidate genes SPARC and LOX.

Author

Korvatska E, Munier FL, Zografos L, Ahmad F, Faggioni R, Dolivo-Beuret A, Uffer S, Pescia G, and Schorderet DF

Subjects
Alleles, Corneal Dystrophies, Hereditary classification, Female, Genetic Linkage, Genetic Markers, Haplotypes, Humans, Male, Models, Genetic, Osteonectin genetics, Pedigree, Protein-Lysine 6-Oxidase genetics, Recombination, Genetic, Switzerland, Chromosomes, Human, Pair 5 genetics, Corneal Dystrophies, Hereditary genetics
Abstract

Granular Groenouw type I (CDGG1) and lattice type 1 (CDL1) corneal dystrophies are two distinct potentially blinding conditions. These two entities were recently mapped to a region on chromosome 5q. We have investigated 2 families of Swiss origin with CDGG1 and CDL1 by linkage analysis. Our data show a maximum lod score of 5.38 at theta = 0.00 for marker D5S393 in CDL1 and 4.17 at theta = 0.00 for D5S658 in CDGG1. When combined, these families show a maximum low score of 9.22 for D5S393 at theta = 0.00. This confirms previous reports. Furthermore, we describe a recombination centromeric to D5S399 in a member of the CDL1 family. Haplotype analysis in the 4 branches of the CDGG1 family demonstrated a common chromosomal region including D5S393 and D5S399 in all the affected members. By combining our data with previously reported mapping information and assuming that CDGG1 and CDL1 are allelic manifestations of the same gene, we can refine the location of the CDGG1/CDL1 gene to a 1-cM region on chromosome 5q. Using candidate genes in the 5q22-q32 interval, we investigated the possibility that mutations in the SPARC or LOX genes cause these corneal diseases. Several recombinations occurred between these two genes and CDGG1/CDL1 in our 2 families, thus excluding this hypothesis.

Published
1996
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18. The human TAX1 gene encoding the axon-associated cell adhesion molecule TAG-1/axonin-1: genomic structure and basic promoter.

Author

Kozlov SV, Giger RJ, Hasler T, Korvatska E, Schorderet DF, and Sonderegger P

Subjects
Animals, Base Sequence, Chickens, Chromosome Mapping, Cloning, Molecular, Contactin 2, Exons, Genes, Reporter, Humans, Introns, Molecular Sequence Data, Repetitive Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, Cell Adhesion Molecules, Neuronal genetics, Promoter Regions, Genetic
Abstract

The human TAX-1 gene (HGMW-approved symbol TAX1) is located on chromosome 1 (1q32.1) and encodes the neuronal cell adhesion molecule TAG-1/axonin-1. The gene product, termed TAG-1 in the rat and axonin-1 in the chicken, is composed of six immunoglobulin (Ig)-like and four fibronectin type III (FNIII)-like domains. It is found predominantly on the axons of particular nerve fiber tracts during neural development, and it has been demonstrated to function as a potent substratum for neurite outgrowth in vitro. Here we report the cloning and structural characterization of the TAX-1 gene. The transcribed region of the TAX-1 gene extends over about 40 kb. Like its chicken homologue, the human TAX-1 gene consists of 23 exons. Two GT/CA microsatellites were localized in the first intron; a polymorphism was found for one of them. Reporter gene analysis with serially truncated fragments of the 5'-flanking region indicated that a 164-bp fragment located immediately upstream of the putative transcription initiation site was sufficient to function as a basal promoter.

Published
1995
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