Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability.
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability.
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DOI：
10.1126/science.abm6222
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发表时间：
2022-07-29
期刊：
影响因子：
56.9
通讯作者：
Abyzov, Alexej
中科院分区：
文献类型：
--
作者：
Bae, Taejeong;Fasching, Liana;Wang, Yifan;Shin, Joo Heon;Suvakov, Milovan;Jang, Yeongjun;Norton, Scott;Dias, Caroline;Mariani, Jessica;Jourdon, Alexandre;Wu, Feinan;Panda, Arijit;Pattni, Reenal;Chahine, Yasmine;Yeh, Rebecca;Roberts, Rosalinda C.;Huttner, Anita;Kleinman, Joel E.;Hyde, Thomas M.;Straub, Richard E.;Walsh, Christopher A.;Network, Brain Somatic Mosaicism;Urban, Alexander E.;Leckman, James F.;Weinberger, Daniel R.;Vaccarino, Flora M.;Abyzov, Alexej
我们分析了131个人脑（44个神经型，19个患有Tourette综合征，9个患有精神分裂症，59个患有自闭症）在全基因组测序超过200倍深度后的体细胞突变。通常，大脑有20到60个可检测的单核苷酸突变，但约6%的大脑含有数百个体细胞突变。超变性与年龄和与癌症有关的基因的破坏性突变有关，在一些大脑中反映了体内克隆扩增。体细胞复制，可能在发育过程中产生，在~5%的正常和患病的大脑中发现，反映了背景诱变。自闭症大脑与发育中大脑增强子样区域中产生假定转录因子结合基序的突变有关。排名靠前的受影响的基序对应于MEIS转录因子，这表明它们参与基因调控和自闭症之间存在潜在联系。对大脑基因组的调查揭示了正常年龄和某些神经精神疾病的体细胞突变程度。
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to over 200X depth. Typically, brains had 20 to 60 detectable single nucleotide mutations but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and in some brains reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS transcription factors, suggesting a potential link between their involvement in gene regulation and autism. A survey of brain genomes revealed the extent of somatic mutations with normal age and with certain neuropsychiatric disorders.
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影响因子：
64.8
作者：
Boix CA;James BT;Park YP;Meuleman W;Kellis M
通讯作者：
Kellis M
DOI：
10.1126/science.aao4426
发表时间：
2018-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lodato MA;Rodin RE;Bohrson CL;Coulter ME;Barton AR;Kwon M;Sherman MA;Vitzthum CM;Luquette LJ;Yandava CN;Yang P;Chittenden TW;Hatem NE;Ryu SC;Woodworth MB;Park PJ;Walsh CA
通讯作者：
Walsh CA
影响因子：
30.8
作者：
Pardiñas AF;Holmans P;Pocklington AJ;Escott-Price V;Ripke S;Carrera N;Legge SE;Bishop S;Cameron D;Hamshere ML;Han J;Hubbard L;Lynham A;Mantripragada K;Rees E;MacCabe JH;McCarroll SA;Baune BT;Breen G;Byrne EM;Dannlowski U;Eley TC;Hayward C;Martin NG;McIntosh AM;Plomin R;Porteous DJ;Wray NR;Caballero A;Geschwind DH;Huckins LM;Ruderfer DM;Santiago E;Sklar P;Stahl EA;Won H;Agerbo E;Als TD;Andreassen OA;Bækvad-Hansen M;Mortensen PB;Pedersen CB;Børglum AD;Bybjerg-Grauholm J;Djurovic S;Durmishi N;Pedersen MG;Golimbet V;Grove J;Hougaard DM;Mattheisen M;Molden E;Mors O;Nordentoft M;Pejovic-Milovancevic M;Sigurdsson E;Silagadze T;Hansen CS;Stefansson K;Stefansson H;Steinberg S;Tosato S;Werge T;GERAD1 Consortium;CRESTAR Consortium;Collier DA;Rujescu D;Kirov G;Owen MJ;O'Donovan MC;Walters JTR
通讯作者：
Walters JTR
DOI：
10.1126/science.abe0981
发表时间：
2021-03-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fasching L;Jang Y;Tomasi S;Schreiner J;Tomasini L;Brady MV;Bae T;Sarangi V;Vasmatzis N;Wang Y;Szekely A;Fernandez TV;Leckman JF;Abyzov A;Vaccarino FM
通讯作者：
Vaccarino FM
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