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7 results on '"Danielle de Paula Moreira"'

1. Mutations in trpγ, the homologue of TRPC6 autism candidate gene, causes autism-like behavioral deficits in Drosophila

Author

Angelina Palacios-Muñoz, Danielle de Paula Moreira, Valeria Silva, Isaac E. García, Francisco Aboitiz, Mehdi Zarrei, Gabriele Campos, Olivia Rennie, Jennifer L. Howe, Evdokia Anagnostou, Patricia Ambrozewic, Stephen W. Scherer, Maria Rita Passos-Bueno, and John Ewer

Subjects
Male, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Drosophila melanogaster, Autism Spectrum Disorder, Mutation, MUTAÇÃO GENÉTICA, TRPC6 Cation Channel, Animals, Female, Drosophila, Autistic Disorder, Molecular Biology
Abstract

Autism Spectrum Disorder (ASD) is characterized by impaired social communication, restricted interests, and repetitive and stereotyped behaviors. The TRPC6 (transient receptor potential channel 6) represents an ASD candidate gene under an oligogenic/multifactorial model based on the initial description and cellular characterization of an individual with ASD bearing a de novo heterozygous mutation disrupting TRPC6, together with the enrichment of disruptive TRPC6 variants in ASD cases as compared to controls. Here, we perform a clinical re-evaluation of the initial non-verbal patient, and also present eight newly reported individuals ascertained for ASD and bearing predicted loss-of-function mutations in TRPC6. In order to understand the consequences of mutations in TRPC6 on nervous system function, we used the fruit fly, Drosophila melanogaster, to show that null mutations in transient receptor gamma (trpγ; the fly gene most similar to TRPC6), cause a number of behavioral defects that mirror features seen in ASD patients, including deficits in social interactions (based on courtship behavior), impaired sleep homeostasis (without affecting the circadian control of sleep), hyperactivity in both young and old flies, and defects in learning and memory. Some defects, most notably in sleep, differed in severity between males and females and became normal with age. Interestingly, hyperforin, a TRPC6 agonist and the primary active component of the St. John’s wort antidepressant, attenuated many of the deficits expressed by trpγ mutant flies. In summary, our results provide further evidence that the TRPC6 gene is a risk factor for ASD. In addition, they show that the behavioral defects caused by mutations in TRPC6 can be modeled in Drosophila, thereby establishing a paradigm to examine the impact of mutations in other candidate genes.

Published
2022
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2. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Author

Gail E. Herman, Jennifer Reichert, Camilla Stoltenberg, Stephen Sanders, Menachem Fromer, Branko Aleksic, Julian Maller, Rachel Nguyen, Utku Norman, J. Jay Gargus, Donna M. Werling, David J. Cutler, Silvia De Rubeis, Kathryn Roeder, Ryan N. Doan, Sherif Gerges, Joseph D. Buxbaum, Per Magnus, Patrick Turley, Moyra Smith, Isaac N. Pessah, Rebecca J. Schmidt, Chiara Fallerini, Michael E. Talkowski, Carla Lintas, Pål Surén, Paige M. Siper, Duncan S. Palmer, Timothy W. Yu, Michael S. Breen, Sven Sandin, Esben Agerbo, Rich Belliveau, Antonio M. Persico, Elaine Cristina Zachi, Matthew W. State, Karoline Teufel, Margaret A. Pericak-Vance, Caitlin E. Carey, Ryan Collins, Lambertus Klei, Lara Tang, Mads V. Hollegaard, Ole Mors, Iuliana Ionita-Laza, Elisa Giorgio, Astanand Jugessur, Gerry Schellenberg, Christopher A. Walsh, A. Ercument Cicek, Caroline Dias, Gun Peggy Knudsen, Louise Gallagher, Elise B. Robinson, Abraham Reichenberg, Judith Miller, Ashley Dumont, Flora Tassone, Grace Schwartz, Peter Szatmari, Jacqueline I. Goldstein, Evelise Riberi, Brian H.Y. Chung, Stephen W. Scherer, Fátima Lopes, Jesslyn Jamison, Thomas Werge, Mara Parellada, Gabriela Soares, Hilary Coon, Shan Dong, Terho Lehtimäki, Norio Ozaki, Lauren A. Weiss, Susan L. Santangelo, F. Kyle Satterstrom, Daniel P. Howrigan, Emily Hansen-Kiss, Anders D. Børglum, Vivek Appadurai, Maria Rita Passos-Bueno, Hailiang Huang, Marcus C.Y. Chan, Eric M. Morrow, Stephen J. Guter, Catalina Betancur, Ditte Demontis, Matthew W. Mosconi, Pierandrea Muglia, Joanna Martin, Jack A. Kosmicki, Christine M. Freitag, Suma Jacob, W. Ian Lipkin, Angel Carracedo, Mark J. Daly, Andreas G. Chiocchetti, Eduarda Montenegro M. de Souza, Carsten Bøcker Pedersen, Isabela Maya Wahys Silva, Elizabeth E. Guerrero, Mafalda Barbosa, A. Jeremy Willsey, Maureen Mulhern, Claire Churchhouse, Raymond K. Walters, Timothy Poterba, Alessandra Renieri, Emilie M. Wigdor, Lauren M. Schmitt, Jennifer L. Moran, Mullin H.C. Yu, Edwin H. Cook, Jiebiao Wang, Behrang Mahjani, Kaitlin E. Samocha, Kaija Puura, Xin He, Ezra Susser, Aarno Palotie, Bernardo Dalla Bernardina, Montserrat Fernández-Prieto, Thomas Damm Als, Mykyta Artomov, Emma Wilkinson, Mads E. Hauberg, Enrico Domenici, Joon Yong An, Christine Søholm Hansen, Somer L. Bishop, Idan Menashe, So Lun Lee, Marianne Giørtz Pedersen, Alfredo Brusco, Nancy J. Minshew, Michael E. Zwick, Jesper Buchhave Poulsen, Elaine T. Lim, Benjamin M. Neale, Harrison Brand, Danielle Halpern, Elisabetta Trabetti, Alexander Kolevzon, Christine Stevens, Aurora Currò, Miia Kaartinen, Gal Meiri, Richard Anney, Søren Dalsgaard, Minshi Peng, Kimberly Chambert, Brooke Sheppard, Yunin Ludena, James S. Sutcliffe, Marie Bækvad-Hansen, Xinyi Xu, Audrey Thurm, Itaru Kushima, Michael Gill, Irva Hertz-Picciotto, Jonatan Pallesen, Stephan Ripke, Dara S. Manoach, Giovanni Battista Ferrero, Nell Maltman, Michael L. Cuccaro, David M. Hougaard, Javier González-Peñas, Wesley K. Thompson, Felecia Cerrato, Danielle de Paula Moreira, Jonas Bybjerg-Grauholm, Alicia R. Martin, Merete Nordentoft, John A. Sweeney, Alfonso Buil, Tarjinder Singh, Bernie Devlin, Jakob Grove, Daniel H. Geschwind, Manuel Mattheisen, Patrícia Maciel, Preben Bo Mortensen, Andrew J. Schork, Ryan Yuen, Christina M. Hultman, Maria del Pilar Trelles, Aparna Bhaduri, Sabine Schlitt, Diego Lopergolo, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Carnegie Mellon University [Pittsburgh] (CMU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of California [San Francisco] (UCSF), University of California, Korea University [Seoul], The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University [Aarhus], Center for Genomics and Personalized Medicine [Aarhus, Denmark] (CGPM), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research [San Francisco, CA, USA], Bilkent University [Ankara], University of California [Irvine] (UCI), Medical Investigation of Neurodevelopmental Disorders Institute [Davis, CA, USA] (MIND), University of California [Davis] (UC Davis), University of California-University of California, Boston Children's Hospital, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Centre National de la Recherche Scientifique (CNRS), University of Illinois [Chicago] (UIC), University of Illinois System, Trinity College Dublin, Vanderbilt University School of Medicine [Nashville], National Institute of Mental Health (NIMH), Emory University School of Medicine, Emory University [Atlanta, GA], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Autism Sequencing Consortium : Branko Aleksic, Richard Anney, Mafalda Barbosa, Somer Bishop, Alfredo Brusco, Jonas Bybjerg-Grauholm, Angel Carracedo, Marcus C.Y. Chan, Andreas G. Chiocchetti, Brian H.Y. Chung, Hilary Coon, Michael L. Cuccaro, Aurora Curro´ , Bernardo Dalla Bernardina, Ryan Doan, Enrico Domenici, Shan Dong, Chiara Fallerini, Montserrat Ferna´ ndez-Prieto, Giovanni Battista Ferrero, Christine M. Freitag, Menachem Fromer, J. Jay Gargus, Daniel Geschwind, Elisa Giorgio, Javier Gonza´ lez-Pen˜ as, Stephen Guter, Danielle Halpern, Emily HansenKiss, Xin He, Gail E. Herman, Irva Hertz-Picciotto, David M. Hougaard, Christina M. Hultman, Iuliana Ionita-Laza, Suma Jacob, Jesslyn Jamison, Astanand Jugessur, Miia Kaartinen, Gun Peggy Knudsen, Alexander Kolevzon, Itaru Kushima, So Lun Lee, Terho Lehtima¨ ki, Elaine T. Lim, Carla Lintas, W. Ian Lipkin, Diego Lopergolo, Fa´ tima Lopes, Yunin Ludena, Patricia Maciel, Per Magnus, Behrang Mahjani, Nell Maltman, Dara S. Manoach, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Eduarda M.S. Montenegro, Danielle Moreira, Eric M. Morrow, Ole Mors, Preben Bo Mortensen, Matthew Mosconi, Pierandrea Muglia, Benjamin M. Neale, Merete Nordentoft, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Margaret Pericak-Vance, Antonio M. Persico, Isaac Pessah, Kaija Puura, Abraham Reichenberg, Alessandra Renieri, Evelise Riberi, Elise B. Robinson, Kaitlin E. Samocha, Sven Sandin, Susan L. Santangelo, Gerry Schellenberg, Stephen W. Scherer, Sabine Schlitt, Rebecca Schmidt, Lauren Schmitt, Isabela M.W. Silva, Tarjinder Singh, Paige M. Siper, Moyra Smith, Gabriela Soares, Camilla Stoltenberg, Pa˚ l Suren, Ezra Susser, John Sweeney, Peter Szatmari, Lara Tang, Flora Tassone, Karoline Teufel, Elisabetta Trabetti, Maria del Pilar Trelles, Christopher A. Walsh, Lauren A. Weiss, Thomas Werge, Donna M. Werling, Emilie M. Wigdor, Emma Wilkinson, A. Jeremy Willsey, Timothy W. Yu, Mullin H.C. Yu, Ryan Yuen, and Elaine Zachi. and iPSYCH-Broad Consortium : e Esben Agerbo, Thomas Damm Als, Vivek Appadurai, Marie Bækvad-Hansen, Rich Belliveau, Alfonso Buil, Caitlin E. Carey, Felecia Cerrato, Kimberly Chambert, Claire Churchhouse, Søren Dalsgaard, Ditte Demontis, Ashley Dumont, Jacqueline Goldstein, Christine S. Hansen, Mads Engel Hauberg, Mads V. Hollegaard, Daniel P. Howrigan, Hailiang Huang, Julian Maller, Alicia R. Martin, Joanna Martin, Manuel Mattheisen, Jennifer Moran, Jonatan Pallesen, Duncan S. Palmer, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Timothy Poterba, Jesper Buchhave Poulsen, Stephan Ripke, Andrew J. Schork, Wesley K. Thompson, Patrick Turley, and Raymond K. Walters., Norman, Utku, Çicek, A. Ercüment, Betancur, Catalina, University of California [San Francisco] (UC San Francisco), University of California (UC), University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki

Subjects
Male, INTELLECTUAL DISABILITY, genetic structures, MESH: Neurons, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Whole Exome Sequencing, Cohort Studies, 0302 clinical medicine, Gene Frequency, Neurobiology, MESH: Gene Expression Regulation, Developmental, Spectrum disorder, Exome, Developmental, genetics, Copy-number variation, excitatory-inhibitory balance, MESH: Cohort Studies, Exome sequencing, Genetics, Cerebral Cortex, Neurons, 0303 health sciences, MESH: Exome, autism spectrum disorder, cell type, cytoskeleton, excitatory neurons, exome sequencing, inhibitory neurons, liability, neurodevelopment, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Autism spectrum disorder, Female, Single-Cell Analysis, AGED 8 YEARS, MESH: Autistic Disorder, UNITED-STATES, GENETIC RISK, Biology, MESH: Phenotype, behavioral disciplines and activities, SAND DOMAIN, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, MESH: Whole Exome Sequencing, MESH: Neurobiology, mental disorders, medicine, MESH: Gene Frequency, Humans, Cell Lineage, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Autistic Disorder, Allele frequency, Case-Control Studies, Mutation, Missense, Gene Expression Regulation, Developmental, SPECTRUM DISORDER, COPY NUMBER VARIATION, 030304 developmental biology, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Cell Lineage, medicine.disease, MESH: Male, MESH: Cerebral Cortex, DISABILITIES MONITORING NETWORK, Gene Expression Regulation, DE-NOVO MUTATIONS, Mutation, Autism, Missense, MESH: Female, 030217 neurology & neurosurgery, MESH: Single-Cell Analysis
Abstract

International audience; We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

Published
2020
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3. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Author

Evelise Riber, Suma Jacob, Isabela Maya Wahys Silva, Edwin H. Cook, Jennifer Reichert, Merete Nordentoft, Jiebiao Wang, Kaitlin E. Samocha, John A. Sweeney, Elaine Cristina Zachi, Brooke Sheppard, Yunin Ludena, Maureen Mulhern, Lambertus Klei, Christina M. Hultman, Branko Aleksic, Paige M. Siper, Nell Maltman, Fátima Lopes, Jesslyn Jamison, Astanand Jugessur, Timothy W. Yu, F. Kyle Satterstrom, Tarjinder Singh, Bernie Devlin, Per Magnus, Mara Parellada, Louise Gallagher, Christine Stevens, Susan L. Santangelo, David J. Cutler, Shan Dong, Margaret A. Pericak-Vance, Norio Ozaki, Camilla Stoltenberg, Matthew W. State, Emma Wilkinson, Lauren A. Weiss, Michael L. Cuccaro, Stephen Sanders, Aparna Bhaduri, Brian H.Y. Chung, Maria del Pilar Trelles, Ezra Susser, Somer L. Bishop, Catalina Betancur, Donna M. Werling, Sabine Schlitt, Diego Lopergolo, Abraham Reichenberg, Judith Miller, Gabriela Soares, Karoline Teufel, David M. Hougaard, Enrico Domenici, Thomas Werge, Terho Lehtimäki, Sherif Gerges, Audrey Thurm, Emily Hansen-Kiss, Christopher T. Walsh, Michael Gill, Maria Rita Passos-Bueno, Aurora Currò, Utku Norman, Nancy J. Minshew, Harrison Brand, Elisa Giorgio, A. Ercument Cicek, Elaine T. Lim, Joseph D. Buxbaum, Chiara Fallerini, Caroline Dias, Miia Kaartinen, Gal Meiri, Rachel Nguyen, Isaac N. Pessah, J. Jay Gargus, Ryan N. Doan, Minshi Peng, Matthew W. Mosconi, Elizabeth E. Guerrero, Michael E. Talkowski, Iuliana Ionita-Laza, Carla Lintas, Gerry Schellenberg, Alessandra Renieri, Marcus C.Y. Chan, Stephen J. Guter, Danielle Halpern, Javier González-Peñas, Flora Tassone, So Lun Lee, Elise B. Robinson, Alfredo Brusco, Danielle de Paula Moreira, Bernardo Dalla Bernardina, Benjamin M. Neale, Gun Peggy Knudsen, Behrang Mahjani, Peter Szatmari, Elisabetta Trabetti, Lauren M. Schmitt, Kaija Puura, Mykyta Artomov, Rebecca J. Schmidt, Michael S. Breen, Mark J. Daly, Joon Yong An, Dara S. Manoach, Grace Schwartz, Hilary Coon, Christine M. Freitag, Andreas G. Chiocchetti, Eduarda Montenegro M. de Souza, Ryan L. Collins, Mafalda Barbosa, Emilie M. Wigdor, Montserrat Fernández-Prieto, Stephen W. Scherer, Anders D. Børglum, Jack A. Kosmicki, W. Ian Lipkin, Mullin H.C. Yu, Michael E. Zwick, Irva Hertz-Picciotto, Kathryn Roeder, Moyra Smith, Gail E. Herman, James S. Sutcliffe, Xinyi Xu, A. Jeremy Willsey, Alexander Kolevzon, Itaru Kushima, Menachem Fromer, Jakob Grove, Patrícia Maciel, Preben Bo Mortensen, Xin He, Aarno Palotie, Silvia De Rubeis, Idan Menashe, Jonas Bybjerg-Grauholm, Pål Surén, Antonio M. Persico, Ole Mors, Sven Sandin, Lara Tang, Eric M. Morrow, Pierandrea Muglia, Angel Carracedo, Ryan Yuen, and Giovanni Battista Ferrero

Subjects
False discovery rate, Regulation of gene expression, Genetics, 0303 health sciences, Biology, medicine.disease, Phenotype, 03 medical and health sciences, 0302 clinical medicine, Autism spectrum disorder, mental disorders, medicine, Autism, Copy-number variation, Gene, 030217 neurology & neurosurgery, Exome sequencing, 030304 developmental biology
Abstract

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

Published
2019
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4. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

Author

Shan Dong, Norio Ozaki, Ryan K. C. Yuen, David J. Cutler, Lauren A. Weiss, Catalina Betancur, Abraham Reichenberg, Hassen-Kiss E, Judith Miller, Brooke Sheppard, Yunin Ludena, Astanand Jugessur, Irva Hertz-Picciotto, Donna M. Werling, Aurora Currò, Isaac N. Pessah, Giovanni Battista Ferrero, Somer L. Bishop, Utku Norman, Nancy J. Minshew, Tarjinder Singh, Bernie Devlin, Michael E. Talkowski, Carla Lintas, Susan L. Santangelo, Miia Kaartinen, Gal Meiri, Camilla Stoltenberg, Stephen Sanders, Sherif Gerges, Michael L. Cuccaro, Ryan N. Doan, Suma Jacob, Matthew W. Mosconi, Lambertus Klei, Michael E. Zwick, Kathryn Roeder, Merete Nordentoft, Lauren M. Schmitt, John A. Sweeney, Elizabeth E. Guerrero, Kaija Puura, Alessandra Renieri, Elaine T. Lim, Maureen Mulhern, Danielle de Paula Moreira, Cicek Ae, Nell Maltman, Aparna Bhaduri, Mara Parellada, Sabine Schlitt, Diego Lopergolo, Gun Peggy Knudsen, Christina M. Hultman, Jesslyn Jamison, Rebecca J. Schmidt, So Lun Lee, Iuliana Ionita-Laza, Peter Szatmari, Gerry Schellenberg, Alfredo Brusco, Christine M. Freitag, Andreas G. Chiocchetti, Javier González-Peñas, Michael S. Breen, Jakob Grove, Ryan L. Collins, Mafalda Barbosa, Emilie M. Wigdor, Elise B. Robinson, Cathy A. Stevens, Gabriela Soares, Benjamin M. Neale, Edwin H. Cook, Jiebiao Wang, David M. Hougaard, Enrico Domenici, Gail E. Herman, Patrícia Maciel, Kaitlin E. Samocha, Preben Bo Mortensen, Stephen W. Scherer, Yu Mhc, Elaine Cristina Zachi, Menachem Fromer, Antonio M. Persico, Anders D. Børglum, Minshi Peng, Megan Smith, Elisabetta Trabetti, Rachel Nguyen, Fátima Lopes, James S. Sutcliffe, Trelles Mdp, Xinyi Xu, Emma Wilkinson, Joseph D. Buxbaum, Audrey Thurm, Chiara Fallerini, Jack A. Kosmicki, Michael Gill, Paige M. Siper, Timothy W. Yu, Grace Schwartz, Thomas Werge, Terho Lehtimäki, Itaru Kushima, Jay Gargus, Dalla Bernardina B, Hilary Coon, Maria Rita Passos-Bueno, Stephen J. Guter, Margaret A. Pericak-Vance, Matthew W. State, Per Magnus, Christopher A. Walsh, Evelise Riberi, Ezra Susser, Xin He, Aarno Palotie, Idan Menashe, Eric M. Morrow, Jonas Bybjerg-Grauholm, Pierandrea Muglia, Pål Surén, De Rubeis S, Angel Carracedo, Sven Sandin, Montse Fernández-Prieto, Lara Tang, Lipkin Wi, Ole Mors, Louise Gallagher, Montenegro M. de Souza E, Brian H.Y. Chung, Anney Rjl, Alexander Kolevzon, Dara S. Manoach, Daniel H. Geschwind, Silva Imw, Caroline Dias, Jeremy Willsey, Jennifer Reichert, Elisa Giorgio, Branko Aleksic, Flora Tassone, Satterstrom Fk, Senthil G, Karoline Teufel, Chan Mcy, Harrison Brand, Danielle Halpern, Behrang Mahjani, Mykyta Artomov, Mark J. Daly, Joon Yong An, and Lehner T

Subjects
Genetics, Regulation of gene expression, 0303 health sciences, medicine.medical_specialty, Neurogenetics, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Autism spectrum disorder, mental disorders, medicine, Autism, Medical genetics, Copy-number variation, Gene, 030217 neurology & neurosurgery, Exome sequencing, 030304 developmental biology
Abstract

SummaryWe present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

Published
2018
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5. Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH)

Author

Débora Romeo Bertola, Maria Rita Passos-Bueno, Kátia Maria da Rocha, Ana Luiza B. Martins, Danielle de Paula Moreira, Naila Cristina Vilaça Lourenço, Isabela Maya Wahys Silva, Carla Rosenberg, Karina Griesi-Oliveira, Eloisa de Sá Moreira, Meire Aguena, Monize Lazar, Silvia S. Costa, Cintia M. Ribeiro, Michel S Naslavsky, Mayana Zatz, Estevão Vadasz, Elaine Cristina Zachi, Agnes Cristina Fett-Conte, Universidade de São Paulo (USP), Universidade Estadual Paulista (Unesp), and Fac Med Sao Jose Rio Preto

Subjects
0301 basic medicine, Candidate gene, TRANSTORNOS GLOBAIS DO DESENVOLVIMENTO INFANTIL, Comparative genomic hybridization, Copy number variation, Autism, Computational biology, medicine.disease, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Neurodevelopmental disorder, SLC17A6, Autism spectrum disorder, mental disorders, Developmental and Educational Psychology, medicine, Multiplex ligation-dependent probe amplification, Copy-number variation, MBD2, Psychology
Abstract

Made available in DSpace on 2018-11-26T17:55:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Autism spectrum disorder (ASD) has a strong genetic basis and advances in genomic scanning methods have resulted in the identification of the underlying alterations in about 30% of the cases. The overwhelming majority of these alterations are either sequencing variants or large copy number variations (CNVs). In this pilot study, we tested whether the use of a customized array comparative genomic hybridization (aCGH), targeting exons of 269 ASD candidate genes, would allow the identification of small potentially pathogenic CNVs (

Published
2016

6. Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Author

Danielle de Paula Moreira, Estevão Vadasz, Kátia Maria da Rocha, Eoghan O’ Halloran, Ana Luiza Bossolani-Martins, Agnes Cristina Fett-Conte, Tiago R. Magalhaes, Naila Cristina Vilaça Lourenço, V.N.V.O. Takahashi, Eloisa de Sá Moreira, Joanna Goes Castro Meira, Débora Romeo Bertola, Karina Griesi-Oliveira, and Maria Rita Passos-Bueno

Subjects
Male, Heredity, Chromosomes, Human, Pair 22, Autism, Epilepsy, Behavioral Neuroscience, Medicine and Health Sciences, Chromosomes, Human, Copy-number variation, Child, Genetics, Multidisciplinary, Genomics, Penetrance, Copy Number Variation, Pedigree, Phenotypes, Autism spectrum disorder, Cytogenetic Analysis, Medicine, Female, Brazil, Research Article, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, DNA Copy Number Variations, Science, Single-nucleotide polymorphism, Genetic Counseling, Biology, Genome Complexity, Genetic Predisposition, Polymorphism, Single Nucleotide, Human Genomics, Chromosomal Inheritance, Cytogenetics, Genetic Disorders, Genomic Medicine, Developmental Neuroscience, mental disorders, medicine, SNP, Humans, Multiplex ligation-dependent probe amplification, Expressivity (genetics), Genetic Testing, Clinical Genetics, Chromosomes, Human, Pair 15, Base Sequence, Quantitative Traits, EPILEPSIA, Biology and Life Sciences, Computational Biology, Human Genetics, medicine.disease, Genome Analysis, Child Development Disorders, Pervasive, Neurodevelopmental Disorders, Genetics of Disease, Chromosomes, Human, Pair 16, Neuroscience
Abstract

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p

Published
2014

7. A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder

Author

Nicole Davis-Wright, Danielle de Paula Moreira, Estevão Vadasz, Guilherme Müller Orabona, Christopher E. Mason, Stephen Sanders, Débora Romeo Bertola, Matthew W. State, Maria Rita Passos-Bueno, and Karina Griesi-Oliveira

Subjects
Adult, Male, DOENÇAS GENÉTICAS, Trisomy, Chromosomal translocation, Chromosomal rearrangement, Biology, Translocation, Genetic, Cellular and Molecular Neuroscience, Pregnancy, Female patient, medicine, Chromosomes, Human, Humans, Child, Genetic Association Studies, Genetics (clinical), Chromosome Aberrations, Gene Rearrangement, Genetics, Chromosomes, Human, X, Infant, Newborn, Chromosome, Genetic Alteration, Uniparental Disomy, medicine.disease, Phenotype, Psychiatry and Mental health, Child Development Disorders, Pervasive, Autism spectrum disorder, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 5, Female
Abstract

Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. © 2012 Wiley Periodicals, Inc.

Published
2012

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