Search

Your search keyword '"Guillermo Casallo"' showing total 7 results
Start Over Author "Guillermo Casallo" Publication Year Range Last 50 years
7 results on '"Guillermo Casallo"'

2. Transcriptome-wide characterization of the endogenous miR-34A-p53 tumor suppressor network

Author

Nicholas W. Fischer, Guillermo Casallo, Anna Pan, Gavin W. Wilson, Badr Id Said, Daniele Merico, Geneviève Deblois, Jean Gariépy, Nardin Samuel, Roumiana Alexandrova, Thomas J. Hudson, David Malkin, Mathieu Lupien, and Tara Paton

Subjects
p53, 0301 basic medicine, medicine.medical_specialty, Cell Survival, DNA Mutational Analysis, non-coding RNA, Cellular homeostasis, Apoptosis, Genomics, Germline, Epigenesis, Genetic, Transcriptome, 03 medical and health sciences, Cell Line, Tumor, Neoplasms, Molecular genetics, microRNA, medicine, Homeostasis, Humans, Genes, Tumor Suppressor, TP53, Epigenetics, Child, Promoter Regions, Genetic, miR-34A, Cell Proliferation, Genetics, Sequence Analysis, RNA, business.industry, Gene Expression Profiling, Cell Cycle, Infant, Non-coding RNA, 3. Good health, MicroRNAs, 030104 developmental biology, Oncology, Child, Preschool, Tumor Suppressor Protein p53, business, Research Paper
Abstract

// Nardin Samuel 1, 2, 3 , Gavin Wilson 3, 4 , Badr Id Said 2 , Anna Pan 2 , Genevieve Deblois 5 , Nicholas W. Fischer 6 , Roumiana Alexandrova 7 , Guillermo Casallo 7 , Tara Paton 7 , Mathieu Lupien 5 , Jean Gariepy 6 , Daniele Merico 7 , Thomas J. Hudson 1, 3, 4 , David Malkin 1, 2, 8 1 Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada 2 Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada 3 Ontario Institute for Cancer Research, Toronto, Canada 4 Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Canada 5 Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 6 Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Canada 7 The Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada 8 Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada Correspondence to: David Malkin, email: david.malkin@sickkids.ca Keywords: miR-34A, p53, TP53, cell cycle, non-coding RNA Received: April 07, 2016 Accepted: May 19, 2016 Published: July 06, 2016 ABSTRACT microRNA-34A is a critical component of the p53 network and expression of miR- 34A is down-regulated by promoter hypermethylation or focal deletions in numerous human cancers. Although miR-34A deregulation may be an important driver in cancer, the endogenous role of this microRNA in cellular homeostasis is not well characterized. To address this knowledge gap, we aimed to determine the transcriptional landscape of the miR-34A-p53 axis in non-transformed cells. Using primary skin-derived fibroblast cell lines from patients who developed childhood cancers, and who harbor either germline TP53 mutations or are TP53 wild type, we sought to characterize the transcriptional response to miR-34A modulation. Through transcriptome-wide RNA-Sequencing, we show for the first time that in human non- transformed cells harboring TP53 mutations, miR-34A functions in a noncanonical manner to influence noncoding RNA networks, including RNA components of the minor (U12) spliceosome, as well as TP53 -dependent and independent epigenetic pathways. miR- 34A-regulated transcripts include known cell cycle mediators and abrogation of miR-34A leads to a TP53 -dependent increase in the fraction of cells in G2/M. Collectively, these results provide a framework for understanding the endogenous role of the miR-34A signaling axis and identify novel transcripts and pathways regulated by the essential miR-34A-p53 tumor suppressor network.

Published
2016
Full Text
View/download PDF

3. De Novo and Rare Inherited Copy-Number Variations in the Hemiplegic Form of Cerebral Palsy

Author

Carolyn Hunt, Richard F. Wintle, Darcy Fehlings, Susan Walker, Daniele Merico, Stephen W. Scherer, Guillermo Casallo, Mohammed Uddin, Lauren Switzer, Gabrielle deVeber, Matthew J. Gazzellone, Ronit Mesterman, Craig Campbell, Dawa Samdup, Pam Frid, Marie Kim, Christian R. Marshall, Jan Willem Gorter, Edward J Higginbotham, Jeffrey R. MacDonald, Anna McCormick, Anne Kawamura, Bhooma Thiruvahindrapuram, Karizma Mawjee, Dimitri J. Stavropoulos, and Mehdi Zarrei

Subjects
DNA copy number variations, Male, 0301 basic medicine, Proband, endocrine system diseases, genetic association studies, hemiplegia, cross-sectional studies, Pediatrics, Whole Exome Sequencing, 0302 clinical medicine, Risk Factors, Genotype, Medicine, Original Research Article, Copy-number variation, Child, Genetics (clinical), Exome sequencing, Hemiplegic cerebral palsy, Genetics, education.field_of_study, pedigree, Pedigree, female, Phenotype, Child, Preschool, Female, microarray, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, DNA Copy Number Variations, phenotype, Population, Hemiplegia, Neuroimaging, preschool, 03 medical and health sciences, PTPRM, Exome Sequencing, mental disorders, Humans, Genetic Predisposition to Disease, education, Genetic Association Studies, Retrospective Studies, Chromosome Aberrations, cerebral palsy, business.industry, Cerebral Palsy, hemiplegic cerebral palsy, Cross-Sectional Studies, copy-number variation, 030104 developmental biology, Etiology, business, 030217 neurology & neurosurgery
Abstract

Purpose Hemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP. Methods We genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (

Published
2018

4. 1778. Epstein–Barr Virus Genetic Diversity: Evaluation of BZLF1 Variants among Bone Marrow Transplant Patients and Individuals with Infectious Mononucleosis

Author

Tal Schechter, Guillermo Casallo, Upton Allen, Nasser Khodai-Booran, Mariana Abdulnoor, and Tara Paton

Subjects
Genetic diversity, Bone marrow transplant, Mononucleosis, business.industry, medicine.disease_cause, medicine.disease, Epstein–Barr virus, BZLF1, Abstracts, Infectious Diseases, Oncology, Immunology, Poster Abstracts, Medicine, business
Abstract

Background Epstein–Barr virus (EBV) is associated with several diseases, including infectious mononucleosis (IM) and malignant disorders, including post-transplant lymphoproliferative disorder (PTLD). The relationship between strains of the virus and disease manifestations or illness severity is of interest. Such strains have been defined by genetic variations in the major viral genes. Data involving the patterns of genetic diversity of the virus in different populations are required. We examined the genetic diversity of the BZLF1 gene, which is a major lytic gene of the virus. Methods We sequenced the BZLF1 gene of EBV following amplification from DNA that was extracted from blood obtained from pediatric bone marrow transplant (BMT) patients and children and young adults with IM. Sequencing was done by Sanger methodology (dideoxy DNA sequencing) and the sequences were aligned with a reference strain of EBV using Geneious software. The variant burden and types of single nucleotide variants (SNV) were compared across the 3 exons of the BZLF1 gene. Results We sequenced the BZLF1 gene using 21 patients with IM (median age 14, age range 2–19 years) and 11 who underwent bone marrow transplantation (median age 6, range 3–13 years). Three of 11 BMT patients developed post-transplant lymphoproliferative disorder (PTLD). Among the 3 exons, exon 1 had the greatest diversity across both study groups. There was a tendency for less diversity among PTLD samples, with no sample containing >1 single nucleotide variant (SNV) in contrast to the other samples. In samples that contained SNVs, there was a non-statistically significant trend for more SNVs to occur among the IM samples compared with PTLD samples (median 4.5 and 0, respectively; P > 0.05). Additionally, 2/11 (18.2%) BMT sequences contained more than 1 SNV compared with 7/21 (33.3%) IM sequences (P > 0.05). Conclusion There was a tendency for more genetic diversity among samples from patients with IM compared with bone marrow transplant patients, notably those with PTLD. Further studies will determine if this tendency is due to selective pressures in the transplant setting, including but not limited to the use of antiviral agents directed at the lytic phase of EBV. Disclosures All authors: No reported disclosures.

Published
2019

5. 657. Epstein–Barr Virus Genetic Diversity in Blood vs. Saliva Samples From Patients with Infectious Mononucleosis

Author

Guillermo Casallo, Tara Paton, Jessica Pietrzyk, Mariana Abdulnoor, Upton Allen, and Nasser Khodai-Booran

Subjects
Genetic diversity, Saliva, Mononucleosis, business.industry, medicine.disease_cause, medicine.disease, Virology, Epstein–Barr virus, Abstracts, Infectious Diseases, Oncology, B. Poster Abstracts, medicine, business
Abstract

Background The Epstein–Barr virus (EBV) is associated with several diseases, including infectious mononucleosis as well as malignant disorders. The relationship between strains of the virus and disease manifestation or illness severity is of interest. Such strains have been defined by genetic variations in the major viral genes. As a first step toward a better understanding of the relationship between strains and clinical outcomes, data are required on the patterns of genetic diversity of the virus in different populations. In this study, we examined the genetic diversity of the BZLF-1 gene, which is a major lytic gene of the virus. Methods We sequenced the BZLF-1 gene of EBV following amplification from DNA that was extracted from blood and saliva from previously healthy Canadian children and young adults with infectious mononucleosis. Sequencing was done by Sanger methodology (dideoxy DNA sequencing) and the sequences were aligned with a reference strain of EBV using Geneious software. The variant burden and types of single nucleotide variants were compared in blood and saliva samples. Results Twenty-six samples were obtained from 24 patients less than 24 years of age (16 saliva and 10 blood samples). Two subjects provided paired blood and saliva samples at the same visit. Among 36 single nucleotide variations (SNVs), 22% were common to both blood and saliva samples. There was a nonstatistically significant trend for more SNVs among blood compared with saliva samples (median 6 and 1, ranges 0–8 and 0–9, respectively). Of the 3 exons of BZLF-1, exon 1 had the greatest frequency of SNVs compared with exons 2 and 3. Among the paired samples of blood and saliva, there were different genetic variants of the BZLF-1 gene in the blood compared with the saliva samples obtained from patients with infectious mononucleosis. Conclusion Among patients with infectious mononucleosis, different genetic variants of EBV may be present in blood compared with saliva. Blood samples revealed viral strains with a tendency for more genetic diversity compared with saliva. The potential compartmentalization of strains is of relevance in sample selection for the evaluation of the potential clinical impact of the genetic diversity of EBV. In addition, the potential impact on disease pathogenesis is of interest. Disclosures All authors: No reported disclosures.

Published
2018

6. A genome-wide scan for common alleles affecting risk for autism

Author

Veronica J. Vieland, Stephen W. Scherer, Elizabeth A. Heron, Barbara Parrini, Jeremy R. Parr, Louise Gallagher, Jeff Munson, Annemarie Poustka, Susan E. Folstein, Irene Drmic, Gudrun Nygren, John P. Rice, Jeff Salt, Simon Wallace, Geraldine Dawson, Daniel H. Geschwind, Annette Estes, Sean Brennan, Alistair T. Pagnamenta, Nancy J. Minshew, Christina Corsello, Jonathan Green, William M. McMahon, Christopher Gillberg, Kathryn Roeder, Lambertus Klei, Anath C. Lionel, Bridget A. Fernandez, Thomas Bourgeron, Ellen M. Wijsman, Gerard D. Schellenberg, Wendy Roberts, Jeremy Goldberg, Frederico Duque, Ghazala Mirza, Sean Ennis, Joana Almeida, Nadine M. Melhem, Jillian P. Casey, Roberta Igliozzi, Ricardo Segurado, Carine Mantoulan, Katy Renshaw, Kai Wang, Andrew D. Paterson, Raffaella Tancredi, Matthew Nicholas Hill, Richard Anney, Christian R. Marshall, Anthony P. Monaco, Linda Lotspeich, Marion Leboyer, Richard Holt, Andrew Pickles, Vlad Kustanovich, William M. Mahoney, Jessica Brian, Inês Sousa, Peter Szatmari, Vanessa Hus, Janine A. Lamb, Hakon Hakonarson, Lonnie Zwaigenbaum, John Tsiantis, David J. Posey, Olena Korvatska, Guillermo Casallo, Rita M. Cantor, Bhooma Thiruvahindrapduram, Nadia Bolshakova, Sven Bölte, Alison K. Merikangas, Brian L. Yaspan, Cecilia Kim, Andrew Crossett, Fritz Poustka, Danielle Zurawiecki, Agatino Battaglia, Sabata C. Lund, Ann P. Thompson, Bennett L. Leventhal, Jessica Rickaby, Zhouzhi Wang, John I. Nurnberger, Astrid M. Vicente, Maretha de Jonge, Tiago R. Magalhaes, Michael L. Cuccaro, Val C. Sheffield, Nuala Sykes, Elena Maestrini, Guiomar Oliveira, Joseph D. Buxbaum, Fred R. Volkmar, Shawn Wood, Magdalena Laskawiec, Katherine Sansom, Herman van Engeland, Jane McGrath, Thomas H. Wassink, Su H. Chu, Elena Bacchelli, Carolyn Noakes, Ann Le Couteur, Catarina Correia, Ohsuke Migita, Bernie Devlin, Hilary Coon, Gillian Baird, Joseph Piven, Tom Berney, Ana Tryfon, Abdul Noor, Patrick Bolton, Latha Soorya, Vera Stoppioni, Stephen J. Guter, Joseph T. Glessner, Michael Gill, Christopher J. McDougle, Anthony J. Bailey, Margaret A. Pericak-Vance, Joachim Hallmayer, Christine M. Freitag, Penny Farrar, Kirsty Wing, Katherine E. Tansey, Bernadette Rogé, Michael Rutter, Christina Strawbridge, Brett S. Abrahams, Kerstin Wittemeyer, Laura J. Bierut, Tara Paton, Emily L. Crawford, Jonathan L. Haines, Alexander Kolevzon, Gillian Hughes, Lili Senman, James S. Sutcliffe, John B. Gilbert, Katerina Papanikolaou, Andrew R. Carson, Lynne E Cochrane, Regina Regan, Judith Miller, Susanne Thomson, Helen McConachie, Daisuke Sato, Richard Delorme, Jiannis Ragoussis, Eric Fombonne, Clara Lajonchere, Judith Conroy, Dalila Pinto, Aparna Prasad, Naisha Shah, Stanley F. Nelson, Sabine M. Klauck, Catalina Betancur, John B. Vincent, Eftichia Duketis, Jennifer L. Howe, Edwin H. Cook, Xiao-Qing Liu, Catherine Lord, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Department of Neurology, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry, University of Oxford [Oxford]-Warneford Hospital, Newcomen Centre, Guy's Hospital [London], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Child and Adolescent Mental Health, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Department of Child and Adolescent Psychiatry, Institute of psychiatry, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Autism Research Unit, University of Toronto-The Hospital for sick children [Toronto] (SickKids), Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Scientific Affairs, Autism Speaks, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], Disciplines of Genetics and Medicine, Memorial University of Newfoundland [St. John's], John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], 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), University of Gothenburg (GU), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario], Manchester Academic Health Sciences Centre, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Department of Medicine, Autism Genetic Resource Exchange, Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), 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), Nathan Kline Institute for Psychiatric Research (NKI), Nathan Kline Institute for Psychiatric Research, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-NYU Child Study Center, Centre d'Etudes et de Recherches en PsychoPathologie, Université Toulouse - Jean Jaurès (UT2J), Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Departments of Psychiatry and Neurology, Department of Psychiatry and Behavioral Sciences, Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), Centre for Addiction and Mental Health, Clarke Institute, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Institutes of Neuroscience and Health and Society, Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Carolina Institute for Developmental Disabilities, Social, Genetic and Developmental Psychiatry Centre, Washington University in Saint Louis (WUSTL), Howard Hughes Medical-Institute Carver College of Medicine-University of Iowa [Iowa City], Neuropsichiatria Infantile, Ospedale Santa Croce, Child Study Centre, Yale University School of Medicine, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], University of Alberta, Physiopathologie des Maladies du Système Nerveux Central, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Departments of Biostatistics and Medicine, This research was primarily supported by Autism Speaks (USA), the Health Research Board (HRB, Ireland), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute, and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health [HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH057881, MH061009, MH06359, MH066673, MH077930, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261], the Canadian Institutes for Health Research (CIHR), Assistance Publique-Hôpitaux de Paris (France), Autistica, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (grant: Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundação Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Médicale (France), Fundação para a Ciência e Tecnologia (Portugal), GlaxoSmithKline-CIHR Pathfinder Chair (Canada), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health [convention 181 of 19.10.2001], the John P Hussman Foundation (USA), McLaughlin Centre (Canada), Netherlands Organization for Scientific Research [Rubicon 825.06.031], Ontario Ministry of Research and Innovation (Canada), Royal Netherlands Academy of Arts and Sciences [TMF/DA/5801], the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award [075491/Z/04 UK]. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422)., University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), 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), University of Oxford, University of Oxford-Warneford Hospital, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Université de Toulouse (UT)-Université de Toulouse (UT), University of Pennsylvania, Betancur, Catalina, Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu SH, Cochrane L, Corsello C, Crawford EL, Crossett A, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Piven J, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, and Hallmayer J.

Subjects
Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Genotype, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Databases, Genetic, Copy-number variation, MESH: Genetic Variation, Genetics (clinical), MESH: Databases, Genetic, Genetics, 0303 health sciences, education.field_of_study, MESH: Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH: European Continental Ancestry Group, Autism spectrum disorders, MESH: DNA Copy Number Variations, Genotyping, DNA Copy Number Variations, Genotype, Population, MESH: Autistic Disorder, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Genetic variation, Humans, Genetic Predisposition to Disease, ddc:610, Allele, Autistic Disorder, SNP association, education, Molecular Biology, Alleles, MESH: Genome, Human, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Genome, Human, MESH: Alleles, Haplotype, Genetic Variation, Genetic architecture, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: Genome-Wide Association Study, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. Author has checked copyright TS 14.06.13 The subscript characters from the abstract have not copied across properly. TS

Published
2010
Full Text
View/download PDF

7. Gene and miRNA expression profiles in autism spectrum disorders

Author

Fuad G. Gwadry, Mohammad Mahdi Ghahramani Seno, Pingzhao Hu, Christian R. Marshall, Dalila Pinto, Guillermo Casallo, and Stephen W. Scherer

Subjects
Male, Rett syndrome, Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Gene duplication, medicine, Gene silencing, Humans, Genetic Predisposition to Disease, Copy-number variation, Child, Molecular Biology, 030304 developmental biology, Genetics, Regulation of gene expression, 0303 health sciences, Genetic heterogeneity, General Neuroscience, Gene Expression Profiling, Gene Expression Regulation, Developmental, Infant, medicine.disease, Developmental disorder, MicroRNAs, Child Development Disorders, Pervasive, Child, Preschool, Autism, Female, Neurology (clinical), 030217 neurology & neurosurgery, Developmental Biology
Abstract

Accumulating data indicate that there is significant genetic heterogeneity underlying the etiology in individuals diagnosed with autism spectrum disorder (ASD). Some rare and highly-penetrant gene variants and copy number variation (CNV) regions including NLGN3, NLGN4, NRXN1, SHANK2, SHANK3, PTCHD1, 1q21.1, maternally-inherited duplication of 15q11-q13, 16p11.2, amongst others, have been identified to be involved in ASD. Genome-wide association studies have identified other apparently low risk loci and in some other cases, ASD arises as a co-morbid phenotype with other medical genetic conditions (e.g. fragile X). The progress studying the genetics of ASD has largely been accomplished using genomic analyses of germline-derived DNA. Here, we used gene and miRNA expression profiling using cell-line derived total RNA to evaluate possible transcripts and networks of molecules involved in ASD. Our analysis identified several novel dysregulated genes and miRNAs in ASD compared with controls, including HEY1, SOX9, miR-486 and miR-181b. All of these are involved in nervous system development and function and some others, for example, are involved in NOTCH signaling networks (e.g. HEY1). Further, we found significant enrichment in molecules associated with neurological disorders such as Rett syndrome and those associated with nervous system development and function including long-term potentiation. Our data will provide a valuable resource for discovery purposes and for comparison to other gene expression-based, genome-wide DNA studies and other functional data.

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results