Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.
复制标题
DOI：
10.1126/science.aaa3650
复制
发表时间：
2015-03-27
期刊：
影响因子：
--
通讯作者：
Goldstein DB
中科院分区：
文献类型：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
肌萎缩侧索硬化症（ALS）是一种严重的神经系统疾病，目前尚无有效的治疗方法。在这里，我们报告了一项中等规模的测序研究的结果，旨在确定有助于ALS易感性的新基因。我们对2，874名ALS患者进行了全外显子组测序，并将其与6，405名对照进行了比较。发现几个已知的ALS基因相关，并且非经典IκB激酶家族TANK结合激酶1（TBK 1）被鉴定为ALS基因。已知TBK 1结合并磷酸化参与先天免疫和自噬的许多蛋白质，包括视神经磷酸酶（OPTN）和p62（SQSTM 1/隔离体），这两者也与ALS有关。这些观察结果揭示了自噬途径在ALS中的关键作用，并提出了治疗干预的具体目标。
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. Here we report the results of a moderate-scale sequencing study aimed at identifying new genes contributing to predisposition for ALS. We performed whole exome sequencing of 2,874 ALS patients and compared them to 6,405 controls. Several known ALS genes were found to be associated, and the non-canonical IκB kinase family TANK-Binding Kinase 1 (TBK1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.
登录
查看更多内容
具有抗癌功效的选择性 TBK1/IKKi 双重抑制剂
影响因子：
6.4
作者：
Li, Jijia;Huang, Jingjia;Jeong, Ji-Hak;Park, Sun-Jin;Wei, Rui;Peng, Jieying;Luo, Zhiyong;Chen, Yen Ting;Feng, Yangbo;Luo, Jun-Li
通讯作者：
Luo, Jun-Li
影响因子：
25
作者：
Chesi, Alessandra;Staahl, Brett T.;Jovicic, Ana;Couthouis, Julien;Fasolino, Maria;Raphael, Alya R.;Yamazaki, Tomohiro;Elias, Laura;Polak, Meraida;Kelly, Crystal;Williams, Kelly L.;Fifita, Jennifer A.;Maragakis, Nicholas J.;Nicholson, Garth A.;King, Oliver D.;Reed, Robin;Crabtree, Gerald R.;Blair, Ian P.;Glass, Jonathan D.;Gitler, Aaron D.
通讯作者：
Gitler, Aaron D.
影响因子：
34.7
作者：
Lee, Edward B.;Lee, Virginia M-Y;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
25
作者：
Johnson, Janel O.;Pioro, Erik P.;Boehringer, Ashley;Chia, Ruth;Feit, Howard;Renton, Alan E.;Pliner, Hannah A.;Abramzon, Yevgeniya;Marangi, Giuseppe;Winborn, Brett J.;Gibbs, J. Raphael;Nalls, Michael A.;Morgan, Sarah;Shoai, Maryam;Hardy, John;Pittman, Alan;Orrell, Richard W.;Malaspina, Andrea;Sidle, Katie C.;Fratta, Pietro;Harms, Matthew B.;Baloh, Robert H.;Pestronk, Alan;Weihl, Conrad C.;Rogaeva, Ekaterina;Zinman, Lorne;Drory, Vivian E.;Borghero, Giuseppe;Mora, Gabriele;Calvo, Andrea;Rothstein, Jeffrey D.;Drepper, Carsten;Sendtner, Michael;Singleton, Andrew B.;Taylor, J. Paul;Cookson, Mark R.;Restagno, Gabriella;Sabatelli, Mario;Bowser, Robert;Chio, Adriano;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
64.5
作者：
Buchan, J. Ross;Kolaitis, Regina-Maria;Parker, Roy
通讯作者：
Parker, Roy