Synaptic, transcriptional and chromatin genes disrupted in autism.
Synaptic, transcriptional and chromatin genes disrupted in autism.
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DOI：
10.1038/nature13772
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发表时间：
2014-11-13
期刊：
影响因子：
64.8
通讯作者：
Buxbaum, Joseph D.
中科院分区：
文献类型：
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作者：
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 G.;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;Lehtimaeki, 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;Rehnstrom, Karola;Reichenberg, Abraham;Sabo, Aniko;Sachse, Michael;Sanders, Stephan J.;Schafer, Chad;Schulte-Ruether, 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.;Skiar, 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.
自闭症谱系障碍的遗传结构涉及常见和罕见变异的相互作用及其对数百个基因的影响。利用外显子组测序，对3,871例自闭症患者和9,937名祖先匹配或父母对照的罕见编码变异进行分析，发现22个常染色体基因的错误发现率(FDR；0.05)，以及一组107个常染色体基因，对那些可能影响风险的基因有强烈的浓缩作用(FDR<；0.30)。这107个基因对突变表现出不同寻常的进化约束，在超过5%的自闭症受试者中导致新的功能丧失突变。许多涉及的基因编码突触、转录和染色质重塑途径的蛋白质。这些包括调节动作电位传播的电压门控离子通道、起搏和兴奋-转录耦合，以及组蛋白修饰酶和染色质重构体，尤其是涉及赖氨酸甲基化/去甲基化的组蛋白翻译后修饰。
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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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
自闭症谱系障碍中基因和细胞途径的收敛性。
影响因子：
9.8
作者：
Pinto D;Delaby E;Merico D;Barbosa M;Merikangas A;Klei L;Thiruvahindrapuram B;Xu X;Ziman R;Wang Z;Vorstman JA;Thompson A;Regan R;Pilorge M;Pellecchia G;Pagnamenta AT;Oliveira B;Marshall CR;Magalhaes TR;Lowe JK;Howe JL;Griswold AJ;Gilbert J;Duketis E;Dombroski BA;De Jonge MV;Cuccaro M;Crawford EL;Correia CT;Conroy J;Conceição IC;Chiocchetti AG;Casey JP;Cai G;Cabrol C;Bolshakova N;Bacchelli E;Anney R;Gallinger S;Cotterchio M;Casey G;Zwaigenbaum L;Wittemeyer K;Wing K;Wallace S;van Engeland H;Tryfon A;Thomson S;Soorya L;Rogé B;Roberts W;Poustka F;Mouga S;Minshew N;McInnes LA;McGrew SG;Lord C;Leboyer M;Le Couteur AS;Kolevzon A;Jiménez González P;Jacob S;Holt R;Guter S;Green J;Green A;Gillberg C;Fernandez BA;Duque F;Delorme R;Dawson G;Chaste P;Café C;Brennan S;Bourgeron T;Bolton PF;Bölte S;Bernier R;Baird G;Bailey AJ;Anagnostou E;Almeida J;Wijsman EM;Vieland VJ;Vicente AM;Schellenberg GD;Pericak-Vance M;Paterson AD;Parr JR;Oliveira G;Nurnberger JI;Monaco AP;Maestrini E;Klauck SM;Hakonarson H;Haines JL;Geschwind DH;Freitag CM;Folstein SE;Ennis S;Coon H;Battaglia A;Szatmari P;Sutcliffe JS;Hallmayer J;Gill M;Cook EH;Buxbaum JD;Devlin B;Gallagher L;Betancur C;Scherer SW
通讯作者：
Scherer SW
影响因子：
5.8
作者：
Lachmann, Alexander;Xu, Huilei;Ma'ayan, Avi
通讯作者：
Ma'ayan, Avi
影响因子：
12.3
作者：
Feng J;Wilkinson M;Liu X;Purushothaman I;Ferguson D;Vialou V;Maze I;Shao N;Kennedy P;Koo J;Dias C;Laitman B;Stockman V;LaPlant Q;Cahill ME;Nestler EJ;Shen L
通讯作者：
Shen L
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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