Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology
Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology
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长读长转录本测序鉴定了 tau 病理转基因模型中内嗅皮层的差异亚型表达
DOI：
10.1101/2023.09.20.558220
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
J. Mill
中科院分区：
文献类型：
--
作者：
Szi Kay Leung;Aaron R. Jeffries;I. Castanho;Rosemary Bamford;K. Moore;E. Dempster;Jonathan T. Brown;Z. Ahmed;P. O'Neill;E. Hannon;J. Mill
越来越多的证据表明，选择性剪接在阿尔茨海默病(AD)中发挥着重要作用，AD是一种毁灭性的神经退行性疾病，涉及过度磷酸化的tau在细胞内聚集。我们使用长阅读序列分析了野生型(WT)和转基因(TG)携带突变形式的人tau基因的小鼠内嗅皮层的转录多样性。整个转录组图谱显示，先前报道的WT和TG小鼠之间的基因水平表达差异反映了特定转录本丰度的变化。对阿尔茨海默病相关基因的超深靶向长阅读cDNA测序揭示了数百种新的异构体，并鉴定了与tau病理发展相关的特定转录本。我们的结果强调了差异转录物使用的重要性，即使在没有基因水平的表达变化的情况下，作为神经病理学发展中基因调控的一种机制。我们的文本注释和用于分析长时间阅读的文本测序数据的新的信息学管道作为资源提供给社区。
Increasing evidence suggests that alternative splicing plays an important role in Alzheimer’s disease (AD), a devastating neurodegenerative disorder involving the intracellular aggregation of hyperphosphorylated tau. We used long-read cDNA sequencing to profile transcript diversity in the entorhinal cortex of wild-type (WT) and transgenic (TG) mice harboring a mutant form of human tau. Whole transcriptome profiling showed that previously reported gene-level expression differences between WT and TG mice reflect changes in the abundance of specific transcripts. Ultradeep targeted long-read cDNA sequencing of genes implicated in AD revealed hundreds of novel isoforms and identified specific transcripts associated with the development of tau pathology. Our results highlight the importance of differential transcript usage, even in the absence of gene-level expression alterations, as a mechanism underpinning gene regulation in the development of neuropathology. Our transcript annotations and a novel informatics pipeline for the analysis of long-read transcript sequencing data are provided as a resource to the community.
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
30.8
作者：
Lambert, Jean-Charles;Ibrahim-Verbaas, Carla A.;Harold, Denise;Naj, Adam C.;Sims, Rebecca;Bellenguez, Celine;Jun, Gyungah;DeStefano, Anita L.;Bis, Joshua C.;Beecham, Gary W.;Grenier-Boley, Benjamin;Russo, Giancarlo;Thornton-Wells, Tricia A.;Jones, Nicola;Smith, Albert V.;Chouraki, Vincent;Thomas, Charlene;Ikram, M. Arfan;Zelenika, Diana;Vardarajan, Badri N.;Kamatani, Yoichiro;Lin, Chiao-Feng;Gerrish, Amy;Schmidt, Helena;Kunkle, Brian;Dunstan, Melanie L.;Ruiz, Agustin;Bihoreau, Marie-Therese;Choi, Seung-Hoan;Reitz, Christiane;Pasquier, Florence;Hollingworth, Paul;Ramirez, Alfredo;Hanon, Olivier;Fitzpatrick, Annette L.;Buxbaum, Joseph D.;Campion, Dominique;Crane, Paul K.;Baldwin, Clinton;Becker, Tim;Gudnason, Vilmundur;Cruchaga, Carlos;Craig, David;Amin, Najaf;Berr, Claudine;Lopez, Oscar L.;De Jager, Philip L.;Deramecourt, Vincent;Johnston, Janet A.;Evans, Denis;Lovestone, Simon;Letenneur, Luc;Moron, Francisco J.;Rubinsztein, David C.;Eiriksdottir, Gudny;Sleegers, Kristel;Goate, Alison M.;Fievet, Nathalie;Huentelman, Matthew J.;Gill, Michael;Brown, Kristelle;Kamboh, M. Ilyas;Keller, Lina;Barberger-Gateau, Pascale;McGuinness, Bernadette;Larson, Eric B.;Green, Robert;Myers, Amanda J.;Dufouil, Carole;Todd, Stephen;Wallon, David;Love, Seth;Rogaeva, Ekaterina;Gallacher, John;St George-Hyslop, Peter;Clarimon, Jordi;Lleo, Alberto;Bayer, Anthony;Tsuang, Debby W.;Yu, Lei;Tsolaki, Magda;Bossu, Paola;Spalletta, Gianfranco;Proitsi, Petroula;Collinge, John;Sorbi, Sandro;Sanchez-Garcia, Florentino;Fox, Nick C.;Hardy, John;Naranjo, Maria Candida Deniz;Bosco, Paolo;Clarke, Robert;Brayne, Carol;Galimberti, Daniela;Mancuso, Michelangelo;Matthews, Fiona;Moebus, Susanne;Mecocci, Patrizia;Del Zompo, Maria;Maier, Wolfgang;Hampel, Harald;Pilotto, Alberto;Bullido, Maria;Panza, Francesco;Caffarra, Paolo;Nacmias, Benedetta;Gilbert, John R.;Mayhaus, Manuel;Lannfelt, Lars;Hakonarson, Hakon;Pichler, Sabrina;Carrasquillo, Minerva M.;Ingelsson, Martin;Beekly, Duane;Alvarez, Victoria;Zou, Fanggeng;Valladares, Otto;Younkin, Steven G.;Coto, Eliecer;Hamilton-Nelson, Kara L.;Gu, Wei;Razquin, Cristina;Pastor, Pau;Mateo, Ignacio;Owen, Michael J.;Faber, Kelley M.;Jonsson, Palmi V.;Combarros, Onofre;O'Donovan, Michael C.;Cantwell, Laura B.;Soininen, Hilkka;Blacker, Deborah;Mead, Simon;Mosley, Thomas H., Jr.;Bennett, David A.;Harris, Tamara B.;Fratiglioni, Laura;Holmes, Clive;de Bruijn, Renee F. A. G.;Passmore, Peter;Montine, Thomas J.;Bettens, Karolien;Rotter, Jerome I.;Brice, Alexis;Morgan, Kevin;Foroud, Tatiana M.;Kukull, Walter A.;Hannequin, Didier;Powell, John F.;Nalls, Michael A.;Ritchie, Karen;Lunetta, Kathryn L.;Kauwe, John S. K.;Boerwinkle, Eric;Riemenschneider, Matthias;Boada, Merce;Hiltunen, Mikko;Martin, Eden R.;Schmidt, Reinhold;Rujescu, Dan;Wang, Li-San;Dartigues, Jean-Francois;Mayeux, Richard;Tzourio, Christophe;Hofman, Albert;Noethen, Markus M.;Graff, Caroline;Psaty, Bruce M.;Jones, Lesley;Haines, Jonathan L.;Holmans, Peter A.;Lathrop, Mark;Pericak-Vance, Margaret A.;Launer, Lenore J.;Farrer, Lindsay A.;van Duijn, Cornelia M.;Van Broeckhoven, Christine;Moskvina, Valentina;Seshadri, Sudha;Williams, Julie;Schellenberg, Gerard D.;Amouyel, Philippe
通讯作者：
Amouyel, Philippe
DOI：
10.1073/pnas.83.11.4044
发表时间：
1986-06-01
影响因子：
11.1
作者：
KOSIK, KS;JOACHIM, CL;SELKOE, DJ
通讯作者：
SELKOE, DJ