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Synaptic, transcriptional, and chromatin genes disrupted in autism

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variation and their impact on hundreds of genes. Using exome sequencing, analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal gene...

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Autores principales: De Rubeis, Silvia, He, Xin, Goldberg, Arthur P., Poultney, Christopher S., Samocha, Kaitlin, Cicek, A Ercument, Kou, Yan, Liu, Li, Fromer, Menachem, Walker, Susan, Singh, Tarjinder, Klei, Lambertus, Kosmicki, Jack, Fu, Shih-Chen, Aleksic, Branko, Biscaldi, Monica, Bolton, Patrick F., Brownfeld, Jessica M., Cai, Jinlu, Campbell, Nicholas J., Carracedo, Angel, Chahrour, Maria H., Chiocchetti, Andreas G., Coon, Hilary, Crawford, Emily L., Crooks, Lucy, Curran, Sarah R., Dawson, Geraldine, Duketis, Eftichia, Fernandez, Bridget A., Gallagher, Louise, Geller, Evan, Guter, Stephen J., Hill, R. Sean, Ionita-Laza, Iuliana, Gonzalez, Patricia Jimenez, Kilpinen, Helena, Klauck, Sabine M., Kolevzon, Alexander, Lee, Irene, Lei, Jing, Lehtimäki, Terho, Lin, Chiao-Feng, Ma'ayan, Avi, Marshall, Christian R., McInnes, Alison L., Neale, Benjamin, Owen, Michael J., Ozaki, Norio, Parellada, Mara, Parr, Jeremy R., Purcell, Shaun, Puura, Kaija, Rajagopalan, Deepthi, Rehnström, Karola, Reichenberg, Abraham, Sabo, Aniko, Sachse, Michael, Sanders, Stephan J., Schafer, Chad, Schulte-Rüther, Martin, Skuse, David, Stevens, Christine, Szatmari, Peter, Tammimies, Kristiina, Valladares, Otto, Voran, Annette, Wang, Li-San, Weiss, Lauren A., Willsey, A. Jeremy, Yu, Timothy W., Yuen, Ryan K.C., Cook, Edwin H., Freitag, Christine M., Gill, Michael, Hultman, Christina M., Lehner, Thomas, Palotie, Aarno, Schellenberg, Gerard D., Sklar, Pamela, State, Matthew W., Sutcliffe, James S., Walsh, Christopher A., Scherer, Stephen W., Zwick, Michael E., Barrett, Jeffrey C., Cutler, David J., Roeder, Kathryn, Devlin, Bernie, Daly, Mark J., Buxbaum, Joseph D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402723/
https://www.ncbi.nlm.nih.gov/pubmed/25363760
http://dx.doi.org/10.1038/nature13772
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author De Rubeis, Silvia
He, Xin
Goldberg, Arthur P.
Poultney, Christopher S.
Samocha, Kaitlin
Cicek, A Ercument
Kou, Yan
Liu, Li
Fromer, Menachem
Walker, Susan
Singh, Tarjinder
Klei, Lambertus
Kosmicki, Jack
Fu, Shih-Chen
Aleksic, Branko
Biscaldi, Monica
Bolton, Patrick F.
Brownfeld, Jessica M.
Cai, Jinlu
Campbell, Nicholas J.
Carracedo, Angel
Chahrour, Maria H.
Chiocchetti, Andreas G.
Coon, Hilary
Crawford, Emily L.
Crooks, Lucy
Curran, Sarah R.
Dawson, Geraldine
Duketis, Eftichia
Fernandez, Bridget A.
Gallagher, Louise
Geller, Evan
Guter, Stephen J.
Hill, R. Sean
Ionita-Laza, Iuliana
Gonzalez, Patricia Jimenez
Kilpinen, Helena
Klauck, Sabine M.
Kolevzon, Alexander
Lee, Irene
Lei, Jing
Lehtimäki, Terho
Lin, Chiao-Feng
Ma'ayan, Avi
Marshall, Christian R.
McInnes, Alison L.
Neale, Benjamin
Owen, Michael J.
Ozaki, Norio
Parellada, Mara
Parr, Jeremy R.
Purcell, Shaun
Puura, Kaija
Rajagopalan, Deepthi
Rehnström, Karola
Reichenberg, Abraham
Sabo, Aniko
Sachse, Michael
Sanders, Stephan J.
Schafer, Chad
Schulte-Rüther, Martin
Skuse, David
Stevens, Christine
Szatmari, Peter
Tammimies, Kristiina
Valladares, Otto
Voran, Annette
Wang, Li-San
Weiss, Lauren A.
Willsey, A. Jeremy
Yu, Timothy W.
Yuen, Ryan K.C.
Cook, Edwin H.
Freitag, Christine M.
Gill, Michael
Hultman, Christina M.
Lehner, Thomas
Palotie, Aarno
Schellenberg, Gerard D.
Sklar, Pamela
State, Matthew W.
Sutcliffe, James S.
Walsh, Christopher A.
Scherer, Stephen W.
Zwick, Michael E.
Barrett, Jeffrey C.
Cutler, David J.
Roeder, Kathryn
Devlin, Bernie
Daly, Mark J.
Buxbaum, Joseph D.
author_facet De Rubeis, Silvia
He, Xin
Goldberg, Arthur P.
Poultney, Christopher S.
Samocha, Kaitlin
Cicek, A Ercument
Kou, Yan
Liu, Li
Fromer, Menachem
Walker, Susan
Singh, Tarjinder
Klei, Lambertus
Kosmicki, Jack
Fu, Shih-Chen
Aleksic, Branko
Biscaldi, Monica
Bolton, Patrick F.
Brownfeld, Jessica M.
Cai, Jinlu
Campbell, Nicholas J.
Carracedo, Angel
Chahrour, Maria H.
Chiocchetti, Andreas G.
Coon, Hilary
Crawford, Emily L.
Crooks, Lucy
Curran, Sarah R.
Dawson, Geraldine
Duketis, Eftichia
Fernandez, Bridget A.
Gallagher, Louise
Geller, Evan
Guter, Stephen J.
Hill, R. Sean
Ionita-Laza, Iuliana
Gonzalez, Patricia Jimenez
Kilpinen, Helena
Klauck, Sabine M.
Kolevzon, Alexander
Lee, Irene
Lei, Jing
Lehtimäki, Terho
Lin, Chiao-Feng
Ma'ayan, Avi
Marshall, Christian R.
McInnes, Alison L.
Neale, Benjamin
Owen, Michael J.
Ozaki, Norio
Parellada, Mara
Parr, Jeremy R.
Purcell, Shaun
Puura, Kaija
Rajagopalan, Deepthi
Rehnström, Karola
Reichenberg, Abraham
Sabo, Aniko
Sachse, Michael
Sanders, Stephan J.
Schafer, Chad
Schulte-Rüther, Martin
Skuse, David
Stevens, Christine
Szatmari, Peter
Tammimies, Kristiina
Valladares, Otto
Voran, Annette
Wang, Li-San
Weiss, Lauren A.
Willsey, A. Jeremy
Yu, Timothy W.
Yuen, Ryan K.C.
Cook, Edwin H.
Freitag, Christine M.
Gill, Michael
Hultman, Christina M.
Lehner, Thomas
Palotie, Aarno
Schellenberg, Gerard D.
Sklar, Pamela
State, Matthew W.
Sutcliffe, James S.
Walsh, Christopher A.
Scherer, Stephen W.
Zwick, Michael E.
Barrett, Jeffrey C.
Cutler, David J.
Roeder, Kathryn
Devlin, Bernie
Daly, Mark J.
Buxbaum, Joseph D.
author_sort De Rubeis, Silvia
collection PubMed
description The genetic architecture of autism spectrum disorder involves the interplay of common and rare variation and their impact on hundreds of genes. Using exome sequencing, analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, and a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic, transcriptional, and chromatin remodeling pathways. These include voltage-gated ion channels regulating propagation of action potentials, pacemaking, and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodelers, prominently histone post-translational modifications involving lysine methylation/demethylation.
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spelling pubmed-44027232015-05-13 Synaptic, transcriptional, and chromatin genes disrupted in autism De Rubeis, Silvia He, Xin Goldberg, Arthur P. Poultney, Christopher S. Samocha, Kaitlin Cicek, A Ercument Kou, Yan Liu, Li Fromer, Menachem Walker, Susan Singh, Tarjinder Klei, Lambertus Kosmicki, Jack Fu, Shih-Chen Aleksic, Branko Biscaldi, Monica Bolton, Patrick F. Brownfeld, Jessica M. Cai, Jinlu Campbell, Nicholas J. Carracedo, Angel Chahrour, Maria H. Chiocchetti, Andreas G. Coon, Hilary Crawford, Emily L. Crooks, Lucy Curran, Sarah R. Dawson, Geraldine Duketis, Eftichia Fernandez, Bridget A. Gallagher, Louise Geller, Evan Guter, Stephen J. Hill, R. Sean Ionita-Laza, Iuliana Gonzalez, Patricia Jimenez Kilpinen, Helena Klauck, Sabine M. Kolevzon, Alexander Lee, Irene Lei, Jing Lehtimäki, Terho Lin, Chiao-Feng Ma'ayan, Avi Marshall, Christian R. McInnes, Alison L. Neale, Benjamin Owen, Michael J. Ozaki, Norio Parellada, Mara Parr, Jeremy R. Purcell, Shaun Puura, Kaija Rajagopalan, Deepthi Rehnström, Karola Reichenberg, Abraham Sabo, Aniko Sachse, Michael Sanders, Stephan J. Schafer, Chad Schulte-Rüther, Martin Skuse, David Stevens, Christine Szatmari, Peter Tammimies, Kristiina Valladares, Otto Voran, Annette Wang, Li-San Weiss, Lauren A. Willsey, A. Jeremy Yu, Timothy W. Yuen, Ryan K.C. Cook, Edwin H. Freitag, Christine M. Gill, Michael Hultman, Christina M. Lehner, Thomas Palotie, Aarno Schellenberg, Gerard D. Sklar, Pamela State, Matthew W. Sutcliffe, James S. Walsh, Christopher A. Scherer, Stephen W. Zwick, Michael E. Barrett, Jeffrey C. Cutler, David J. Roeder, Kathryn Devlin, Bernie Daly, Mark J. Buxbaum, Joseph D. Nature Article The genetic architecture of autism spectrum disorder involves the interplay of common and rare variation and their impact on hundreds of genes. Using exome sequencing, analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, and a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic, transcriptional, and chromatin remodeling pathways. These include voltage-gated ion channels regulating propagation of action potentials, pacemaking, and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodelers, prominently histone post-translational modifications involving lysine methylation/demethylation. 2014-10-29 2014-11-13 /pmc/articles/PMC4402723/ /pubmed/25363760 http://dx.doi.org/10.1038/nature13772 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
De Rubeis, Silvia
He, Xin
Goldberg, Arthur P.
Poultney, Christopher S.
Samocha, Kaitlin
Cicek, A Ercument
Kou, Yan
Liu, Li
Fromer, Menachem
Walker, Susan
Singh, Tarjinder
Klei, Lambertus
Kosmicki, Jack
Fu, Shih-Chen
Aleksic, Branko
Biscaldi, Monica
Bolton, Patrick F.
Brownfeld, Jessica M.
Cai, Jinlu
Campbell, Nicholas J.
Carracedo, Angel
Chahrour, Maria H.
Chiocchetti, Andreas G.
Coon, Hilary
Crawford, Emily L.
Crooks, Lucy
Curran, Sarah R.
Dawson, Geraldine
Duketis, Eftichia
Fernandez, Bridget A.
Gallagher, Louise
Geller, Evan
Guter, Stephen J.
Hill, R. Sean
Ionita-Laza, Iuliana
Gonzalez, Patricia Jimenez
Kilpinen, Helena
Klauck, Sabine M.
Kolevzon, Alexander
Lee, Irene
Lei, Jing
Lehtimäki, Terho
Lin, Chiao-Feng
Ma'ayan, Avi
Marshall, Christian R.
McInnes, Alison L.
Neale, Benjamin
Owen, Michael J.
Ozaki, Norio
Parellada, Mara
Parr, Jeremy R.
Purcell, Shaun
Puura, Kaija
Rajagopalan, Deepthi
Rehnström, Karola
Reichenberg, Abraham
Sabo, Aniko
Sachse, Michael
Sanders, Stephan J.
Schafer, Chad
Schulte-Rüther, Martin
Skuse, David
Stevens, Christine
Szatmari, Peter
Tammimies, Kristiina
Valladares, Otto
Voran, Annette
Wang, Li-San
Weiss, Lauren A.
Willsey, A. Jeremy
Yu, Timothy W.
Yuen, Ryan K.C.
Cook, Edwin H.
Freitag, Christine M.
Gill, Michael
Hultman, Christina M.
Lehner, Thomas
Palotie, Aarno
Schellenberg, Gerard D.
Sklar, Pamela
State, Matthew W.
Sutcliffe, James S.
Walsh, Christopher A.
Scherer, Stephen W.
Zwick, Michael E.
Barrett, Jeffrey C.
Cutler, David J.
Roeder, Kathryn
Devlin, Bernie
Daly, Mark J.
Buxbaum, Joseph D.
Synaptic, transcriptional, and chromatin genes disrupted in autism
title Synaptic, transcriptional, and chromatin genes disrupted in autism
title_full Synaptic, transcriptional, and chromatin genes disrupted in autism
title_fullStr Synaptic, transcriptional, and chromatin genes disrupted in autism
title_full_unstemmed Synaptic, transcriptional, and chromatin genes disrupted in autism
title_short Synaptic, transcriptional, and chromatin genes disrupted in autism
title_sort synaptic, transcriptional, and chromatin genes disrupted in autism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402723/
https://www.ncbi.nlm.nih.gov/pubmed/25363760
http://dx.doi.org/10.1038/nature13772
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