Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
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自闭症谱系障碍中基因和细胞途径的收敛性。
DOI：
10.1016/j.ajhg.2014.03.018
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发表时间：
2014-05-01
影响因子：
9.8
通讯作者：
Scherer SW
中科院分区：
文献类型：
--
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
罕见的拷贝数变异(CNV)是自闭症谱系障碍(ASDS)的重要风险来源。我们分析了2,446个受ASD影响的家系，证实了受影响组与对照组相比存在过量的基因缺失和复制(1.41倍，p=1.0亿×10−5)，并且受影响的受试者携带外显子致病CNV的数量增加，重叠与显性或X连锁自闭症和智能障碍相关的已知基因座(优势比=12.62，p=2.7亿×10−15，∼为自闭症受试者的3%)。致病CNV通常表现出不同的表达能力，包括36个座位上罕见的从头和遗传事件，涉及先前与其他神经发育障碍相关的ASD相关基因(CHD2、HDAC4和GDI1)，以及其他基因如SETD5、MIR137和HDAC9。与假设的性别特定的调节因素一致，患有自闭症的女性更有可能患有高穿透性CNV(p=0.017)，并且在脆性X综合征蛋白靶标的受试者中也被过度表达(p=0.02)。受新生CNV和/或功能丧失单核苷酸变体影响的基因聚集在与神经元信号和发育、突触功能和染色质调节相关的网络上。
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10−5) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10−15, ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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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
影响因子：
7.8
作者：
Albertinazzi, C;Gilardelli, D;de Curtis, I
通讯作者：
de Curtis, I
DOI：
10.1523/jneurosci.0402-10.2010
发表时间：
2010-08-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gross C;Nakamoto M;Yao X;Chan CB;Yim SY;Ye K;Warren ST;Bassell GJ
通讯作者：
Bassell GJ
影响因子：
3.5
作者：
Anney R;Klei L;Pinto D;Almeida J;Bacchelli E;Baird G;Bolshakova N;Bölte S;Bolton PF;Bourgeron T;Brennan S;Brian J;Casey J;Conroy J;Correia C;Corsello C;Crawford EL;de Jonge M;Delorme R;Duketis E;Duque F;Estes A;Farrar P;Fernandez BA;Folstein SE;Fombonne E;Gilbert J;Gillberg C;Glessner JT;Green A;Green J;Guter SJ;Heron EA;Holt R;Howe JL;Hughes G;Hus V;Igliozzi R;Jacob S;Kenny GP;Kim C;Kolevzon A;Kustanovich V;Lajonchere CM;Lamb JA;Law-Smith M;Leboyer M;Le Couteur A;Leventhal BL;Liu XQ;Lombard F;Lord C;Lotspeich L;Lund SC;Magalhaes TR;Mantoulan C;McDougle CJ;Melhem NM;Merikangas A;Minshew NJ;Mirza GK;Munson J;Noakes C;Nygren G;Papanikolaou K;Pagnamenta AT;Parrini B;Paton T;Pickles A;Posey DJ;Poustka F;Ragoussis J;Regan R;Roberts W;Roeder K;Roge B;Rutter ML;Schlitt S;Shah N;Sheffield VC;Soorya L;Sousa I;Stoppioni V;Sykes N;Tancredi R;Thompson AP;Thomson S;Tryfon A;Tsiantis J;Van Engeland H;Vincent JB;Volkmar F;Vorstman JA;Wallace S;Wing K;Wittemeyer K;Wood S;Zurawiecki D;Zwaigenbaum L;Bailey AJ;Battaglia A;Cantor RM;Coon H;Cuccaro ML;Dawson G;Ennis S;Freitag CM;Geschwind DH;Haines JL;Klauck SM;McMahon WM;Maestrini E;Miller J;Monaco AP;Nelson SF;Nurnberger JI Jr;Oliveira G;Parr JR;Pericak-Vance MA;Piven J;Schellenberg GD;Scherer SW;Vicente AM;Wassink TH;Wijsman EM;Betancur C;Buxbaum JD;Cook EH;Gallagher L;Gill M;Hallmayer J;Paterson AD;Sutcliffe JS;Szatmari P;Vieland VJ;Hakonarson H;Devlin B
通讯作者：
Devlin B
影响因子：
4.5
作者：
Huang N;Lee I;Marcotte EM;Hurles ME
通讯作者：
Hurles ME