Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium.
Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium.
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DOI：
10.1038/ng.3901
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发表时间：
2017-08
期刊：
影响因子：
30.8
通讯作者：
Smedley D
中科院分区：
文献类型：
--
作者：
Meehan TF;Conte N;West DB;Jacobsen JO;Mason J;Warren J;Chen CK;Tudose I;Relac M;Matthews P;Karp N;Santos L;Fiegel T;Ring N;Westerberg H;Greenaway S;Sneddon D;Morgan H;Codner GF;Stewart ME;Brown J;Horner N;International Mouse Phenotyping Consortium;Haendel M;Washington N;Mungall CJ;Reynolds CL;Gallegos J;Gailus-Durner V;Sorg T;Pavlovic G;Bower LR;Moore M;Morse I;Gao X;Tocchini-Valentini GP;Obata Y;Cho SY;Seong JK;Seavitt J;Beaudet AL;Dickinson ME;Herault Y;Wurst W;de Angelis MH;Lloyd KCK;Flenniken AM;Nutter LMJ;Newbigging S;McKerlie C;Justice MJ;Murray SA;Svenson KL;Braun RE;White JK;Bradley A;Flicek P;Wells S;Skarnes WC;Adams DJ;Parkinson H;Mallon AM;Brown SDM;Smedley D
尽管下一代测序已经彻底改变了将变异与人类疾病联系起来的能力，但由于我们缺乏对大多数基因的功能和病理生物学机制的了解，诊断率和新疗法的开发仍然受到限制。为了应对这一挑战，国际小鼠表型联盟(IMPC)正在创建一个全基因组和全表型的基因功能目录，方法是通过一系列标准化的表型测试，在不同的生物系统中鉴定新的基因敲除小鼠品系，所有小鼠都可以随时提供给生物医学界。分析最初的3328个基因揭示了360种疾病的模型，包括第一种C型Bernard-Soulier、Bardet-Biedl-5和Gordon Holmes综合征。我们90%的表型注释是新的，为1092个基因和未解决的疾病(如致心律失常性右室发育不良3)的候选基因提供了第一个功能证据。最后，我们用100,000个基因组和其他项目描述了我们在变异功能验证中的作用。
Although next generation sequencing has revolutionised the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by our lack of knowledge of function and pathobiological mechanism for most genes. To address this challenge, the International Mouse Phenotyping Consortium (IMPC) is creating a genome- and phenome-wide catalogue of gene function by characterizing new knockout mouse strains across diverse biological systems through a broad set of standardised phenotyping tests, with all mice made readily available to the biomedical community. Analysing the first 3328 genes reveals models for 360 diseases including the first for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations are novel, providing the first functional evidence for 1092 genes and candidates in unsolved diseases such as Arrhythmogenic Right Ventricular Dysplasia 3. Finally, we describe our role in variant functional validation with the 100,000 Genomes and other projects.
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影响因子：
3.9
作者：
Boria, Ilenia;Garelli, Emanuela;Gazda, Hanna T.;Aspesi, Anna;Quarello, Paola;Pavesi, Elisa;Ferrante, Daniela;Meerpohl, Joerg J.;Kartal, Mutlu;Da Costa, Lydie;Proust, Alexis;Leblanc, Thierry;Simansour, Maud;Dahl, Niklas;Froejmark, Anne-Sophie;Pospisilova, Dagmar;Cmejla, Radek;Beggs, Alan H.;Sheen, Mee R.;Landowski, Michael;Buros, Christopher M.;Clinton, Catherine M.;Dobson, Lori J.;Vlachos, Adrianna;Atsidaftos, Eva;Lipton, Jeffrey M.;Ellis, Steven R.;Ramenghi, Ugo;Dianzani, Irma
通讯作者：
Dianzani, Irma
影响因子：
14.9
作者：
Köhler S;Vasilevsky NA;Engelstad M;Foster E;McMurry J;Aymé S;Baynam G;Bello SM;Boerkoel CF;Boycott KM;Brudno M;Buske OJ;Chinnery PF;Cipriani V;Connell LE;Dawkins HJ;DeMare LE;Devereau AD;de Vries BB;Firth HV;Freson K;Greene D;Hamosh A;Helbig I;Hum C;Jähn JA;James R;Krause R;F Laulederkind SJ;Lochmüller H;Lyon GJ;Ogishima S;Olry A;Ouwehand WH;Pontikos N;Rath A;Schaefer F;Scott RH;Segal M;Sergouniotis PI;Sever R;Smith CL;Straub V;Thompson R;Turner C;Turro E;Veltman MW;Vulliamy T;Yu J;von Ziegenweidt J;Zankl A;Züchner S;Zemojtel T;Jacobsen JO;Groza T;Smedley D;Mungall CJ;Haendel M;Robinson PN
通讯作者：
Robinson PN
影响因子：
3.7
作者：
Karp NA;Melvin D;Sanger Mouse Genetics Project;Mott RF
通讯作者：
Mott RF
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA
影响因子：
4.6
作者：
Kizil, Caghan;Kuechler, Beate;Antos, Christopher L.
通讯作者：
Antos, Christopher L.