Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.
Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.
复制标题
DOI：
10.1016/j.cell.2013.06.022
复制
发表时间：
2013-07-18
期刊：
影响因子：
64.5
通讯作者：
Steel KP
中科院分区：
文献类型：
--
作者：
White JK;Gerdin AK;Karp NA;Ryder E;Buljan M;Bussell JN;Salisbury J;Clare S;Ingham NJ;Podrini C;Houghton R;Estabel J;Bottomley JR;Melvin DG;Sunter D;Adams NC;Sanger Institute Mouse Genetics Project;Tannahill D;Logan DW;Macarthur DG;Flint J;Mahajan VB;Tsang SH;Smyth I;Watt FM;Skarnes WC;Dougan G;Adams DJ;Ramirez-Solis R;Bradley A;Steel KP
整个生物体的突变是在现实环境中询问基因功能的有力方法。我们描述了一个项目，桑格研究所小鼠遗传学项目，它为敲除所有基因和筛选每行广泛特征的目标提供了一步。我们发现迄今为止未发表的基因与已知基因一样可能揭示表型，这表明新基因为研究疾病的分子基础提供了丰富的资源。我们发现了许多意想不到的表型，因为我们对它们进行了筛选，强调了筛选广泛性状的所有突变体的价值。单倍不全和多效性都非常普遍。42%的基因对生存能力至关重要，与其他基因相比，这些基因不太可能有相似之处，更有可能形成蛋白质复合物。表型数据和超过900个突变体可供进一步分析。大量公开可用的靶向小鼠突变体和表型数据资源筛选广泛的疾病特征和性状许多新的表型表明已研究和未研究的基因的功能单倍不全和多效性是常见的。超过900个新的突变小鼠系和多方面的表型筛选平台揭示了意想不到的多效性、单倍不全的广泛影响、潜在的疾病模型和未研究基因的功能。
Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. Large openly available resource of targeted mouse mutants and phenotypic data Screen for broad range of disease features and traits Many novel phenotypes suggest functions for both studied and unstudied genes Haploinsufficiency and pleiotropy are common More than 900 new mutant mice lines and a multifaceted phenotypic screening platform reveal unanticipated pleiotropies, widespread effects of haploinsufficiency, potential disease models, and functions for unstudied genes.
登录
查看更多内容
DOI：
10.1126/science.1215040
发表时间：
2012-02-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
MacArthur DG;Balasubramanian S;Frankish A;Huang N;Morris J;Walter K;Jostins L;Habegger L;Pickrell JK;Montgomery SB;Albers CA;Zhang ZD;Conrad DF;Lunter G;Zheng H;Ayub Q;DePristo MA;Banks E;Hu M;Handsaker RE;Rosenfeld JA;Fromer M;Jin M;Mu XJ;Khurana E;Ye K;Kay M;Saunders GI;Suner MM;Hunt T;Barnes IH;Amid C;Carvalho-Silva DR;Bignell AH;Snow C;Yngvadottir B;Bumpstead S;Cooper DN;Xue Y;Romero IG;1000 Genomes Project Consortium;Wang J;Li Y;Gibbs RA;McCarroll SA;Dermitzakis ET;Pritchard JK;Barrett JC;Harrow J;Hurles ME;Gerstein MB;Tyler-Smith C
通讯作者：
Tyler-Smith C
影响因子：
2.5
作者：
Laughlin, Maren R.;Lloyd, K. C. Kent;Cline, Gary W.;Wasserman, David H.
通讯作者：
Wasserman, David H.
DOI：
10.4049/jimmunol.1200282
发表时间：
2012-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nijnik A;Clare S;Hale C;Chen J;Raisen C;Mottram L;Lucas M;Estabel J;Ryder E;Adissu H;Sanger Mouse Genetics Project;Adams NC;Ramirez-Solis R;White JK;Steel KP;Dougan G;Hancock RE
通讯作者：
Hancock RE
影响因子：
6.5
作者：
Fischer, Heinz;Szabo, Sandra;Scherz, Jennifer;Jaeger, Karin;Rossiter, Heidemarie;Buchberger, Maria;Ghannadan, Minoo;Hermann, Marcela;Theussl, Hans-Christian;Tobin, Desmond J.;Wagner, Erwin F.;Tschachler, Erwin;Eckhart, Leopold
通讯作者：
Eckhart, Leopold
影响因子：
2.5
作者：
Fuchs, Helmut;Gailus-Durner, Valerie;Neschen, Susanne;Adler, Thure;Afonso, Luciana Caminha;Aguilar-Pimentel, Juan Antonio;Becker, Lore;Bohla, Alexander;Calzada-Wack, Julia;Cohrs, Christian;Dewert, Anna;Fridrich, Barbara;Garrett, Lillian;Glasl, Lisa;Goetz, Alexander;Hans, Wolfgang;Hoelter, Sabine M.;Horsch, Marion;Hurt, Anja;Janas, Eva;Janik, Dirk;Kahle, Melanie;Kistler, Martin;Klein-Rodewald, Tanja;Lengger, Christoph;Ludwig, Tonia;Maier, Holger;Marschall, Susan;Micklich, Kateryna;Moeller, Gabriele;Naton, Beatrix;Prehn, Cornelia;Puk, Oliver;Racz, Ildiko;Raess, Michael;Rathkolb, Birgit;Rozman, Jan;Scheerer, Markus;Schiller, Evelyn;Schrewe, Anja;Steinkamp, Ralph;Stoeger, Claudia;Sun, Minxuan;Szymczak, Wilfried;Treise, Irina;Panesso, Ingrid Liliana Vargas;Vernaleken, Alexandra M.;Willershaeuser, Monja;Wolff-Muscate, Annemarie;Zeh, Ramona;Adamski, Jerzy;Beckers, Johannes;Bekeredjian, Raffi;Busch, Dirk H.;Eickelberg, Oliver;Favor, Jack;Graw, Jochen;Hoefler, Heinz;Hoeschen, Christoph;Katus, Hugo;Klingenspor, Martin;Klopstock, Thomas;Neff, Frauke;Ollert, Markus;Schulz, Holger;Stoeger, Tobias;Wolf, Eckhard;Wurst, Wolfgang;Yildirim, Ali Onder;Zimmer, Andreas;de Angelis, Martin Hrabe
通讯作者：
de Angelis, Martin Hrabe