De novo gene disruptions in children on the autistic spectrum.
De novo gene disruptions in children on the autistic spectrum.
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DOI：
10.1016/j.neuron.2012.04.009
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发表时间：
2012-04-26
期刊：
影响因子：
16.2
通讯作者：
Wigler M
中科院分区：
文献类型：
--
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
对343个家庭进行外显子组测序，每个家庭都有一个自闭症谱系的孩子和至少一个未受影响的兄弟姐妹，揭示了从头开始的小indel和点替换，这些插入缺失和点替换主要来自父系，并且具有年龄依赖性。我们没有看到受影响的儿童与未受影响的儿童相比有更多的从头错义突变，但基因破坏突变（无义，剪接位点和移码）的频率是两倍，59到28。基于这种差异以及我们和类似研究中发现的基因破坏的复发和总靶点的数量，我们估计有350到400个自闭症易感基因。在这些研究中，许多被破坏的基因与脆性X蛋白FMRP有关，加强了自闭症和突触可塑性之间的联系。我们发现FMRP相关基因比其余基因受到更大的纯化选择，并表明它们是认知障碍的剂量敏感性靶点。
Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.
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影响因子：
14.9
作者：
Blake JA;Bult CJ;Kadin JA;Richardson JE;Eppig JT;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin
影响因子：
64.8
作者：
Fujiki, Ryoji;Chikanishi, Toshihiro;Kato, Shigeaki
通讯作者：
Kato, Shigeaki
DOI：
10.1073/pnas.0701722105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Feldman, Igor;Rzhetsky, Andrey;Vitkup, Dennis
通讯作者：
Vitkup, Dennis
影响因子：
64.5
作者：
Darnell JC;Van Driesche SJ;Zhang C;Hung KY;Mele A;Fraser CE;Stone EF;Chen C;Fak JJ;Chi SW;Licatalosi DD;Richter JD;Darnell RB
通讯作者：
Darnell RB