1. Identification of genetic elements in metabolism by high-throughput mouse phenotyping
- Author
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Rozman, Jan, Rathkolb, Birgit, Meehan, Terrence F, Codner, Gemma F, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Loeffler, Jorik, Stewart, Michelle E, Ramirez-Solis, Ramiro, Mason, Jeremy, Bradley, Allan, Skarnes, William C, Steel, Karen P, Maguire, Simon A, Dench, Joshua, Lafont, David, Vancollie, Valerie E, Pearson, Selina A, Gates, Amy S, Sanderson, Mark, Haselimashhadi, Hamed, Shannon, Carl, Anthony, Lauren F E, Sumowski, Maksymilian T, McLaren, Robbie S B, Doe, Brendan, Wardle-Jones, Hannah, Griffiths, Mark N D, Galli, Antonella, Swiatkowska, Agnieszka, Isherwood, Christopher M, Consortium, IMPC, Speak, Anneliese O, Cambridge, Emma L, Wilson, Heather M, Caetano, Susana S, Maguire, Anna Karin B, Adams, David J, Bottomley, Joanna, Ryder, Ed, Gleeson, Diane, Pouilly, Laurent, Hough, Tertius, Rousseau, Stephane, Auburtin, Aurélie, Reilly, Patrick, Ayadi, Abdel, Selloum, Mohammed, Wood, Joshua A, Clary, Dave, Havel, Peter, Tolentino, Todd, Tolentino, Heather, Mallon, Ann-Marie, Schuchbauer, Mike, Pedroia, Sheryl, Trainor, Amanda, Djan, Esi, Pham, Milton, Huynh, Alison, De Vera, Vincent, Seavitt, John, Gallegos, Juan, Garza, Arturo, Wells, Sara, Mangin, Elise, Senderstrom, Joel, Lazo, Iride, Mowrey, Kate, Bohat, Ritu, Samaco, Rodney, Veeraragavan, Surabi, Beeton, Christine, Kalaga, Sowmya, Kelsey, Lois, Santos, Luis, Vukobradovic, Igor, Berberovic, Zorana, Owen, Celeste, Qu, Dawei, Guo, Ruolin, Newbigging, Susan, Morikawa, Lily, Law, Napoleon, Shang, Xueyuan, Feugas, Patricia, Lelliott, Christopher J, Wang, Yanchun, Eskandarian, Mohammad, Zhu, Yingchun, Penton, Patricia, Laurin, Valerie, Clarke, Shannon, Lan, Qing, Sleep, Gillian, Creighton, Amie, Jacob, Elsa, White, Jacqueline K, Danisment, Ozge, Gertsenstein, Marina, Pereira, Monica, MacMaster, Suzanne, Tondat, Sandra, Carroll, Tracy, Cabezas, Jorge, Hunter, Jane, Clark, Greg, Bubshait, Mohammed, Oestereicher, Manuela A, Sorg, Tania, Miller, David, Sohel, Khondoker, Adissu, Hibret, Ganguly, Milan, Bezginov, Alexandr, Chiani, Francesco, Di Pietro, Chiara, Di Segni, Gianfranco, Ermakova, Olga, Ferrara, Filomena, Champy, Marie-France, Fruscoloni, Paolo, Gambadoro, Aalessia, Gastaldi, Serena, Golini, Elisabetta, La Sala, Gina, Mandillo, Silvia, Marazziti, Daniela, Massimi, Marzia, Matteoni, Rafaele, Orsini, Tiziana, Bower, Lynette R, Pasquini, Miriam, Raspa, Marcello, Rauch, Aline, Rossi, Gianfranco, Rossi, Nicoletta, Putti, Sabrina, Scavizzi, Ferdinando, Tocchini-Valentini, Giuseppe D, Wakana, Shigeharu, Suzuki, Tomohiro, Reynolds, Corey L, Tamura, Masaru, Kaneda, Hideki, Furuse, Tamio, Kobayashi, Kimio, Miura, Ikuo, Yamada, Ikuko, Obata, Yuichi, Yoshiki, Atsushi, Ayabe, Shinya, Chambers, J Nicole, Flenniken, Ann M, Chalupsky, Karel, Seisenberger, Claudia, Bürger, Antje, Beig, Joachim, Kühn, Ralf, Hörlein, Andreas, Schick, Joel, Oritz, Oskar, Giesert, Florian, Graw, Jochen, Murray, Stephen A, Ollert, Markus, Schmidt-Weber, Carsten, Stoeger, Tobias, Önder Yildirim, Ali, Eickelberg, Oliver, Klopstock, Thomas, Busch, Dirk H, Bekeredjian, Raffi, Zimmer, Andreas, Jacobsen, Jules O, Nutter, Lauryl M J, Smedley, Damian, Dickinson, Mary E, Benso, Frank, Morse, Iva, Kim, Hyoung-Chin, Lee, Ho, Cho, Soo Young, Svenson, Karen L, West, David, Tocchini-Valentini, Glauco P, Schütt, Christine, Beaudet, Arthur L, Bosch, Fatima, Braun, Robert B, Dobbie, Michael S, Gao, Xiang, Herault, Yann, Moshiri, Ala, Moore, Bret A, Kent Lloyd, K. C., McKerlie, Colin, Ravindranath, Aakash Chavan, Masuya, Hiroshi, Tanaka, Nobuhiko, Flicek, Paul, Parkinson, Helen E, Sedlacek, Radislav, Seong, Je Kyung, Wang, Chi-Kuang Leo, Moore, Mark, Brown, Steve D, Tschöp, Matthias H, Leuchtenberger, Stefanie, Wurst, Wolfgang, Klingenspor, Martin, Wolf, Eckhard, Beckers, Johannes, Machicao, Fausto, Peter, Andreas, Staiger, Harald, Häring, Hans-Ulrich, Grallert, Harald, Campillos, Monica, Sharma, Sapna, Maier, Holger, Fuchs, Helmut, Gailus-Durner, Valerie, Werner, Thomas, Hrabe de Angelis, Martin, Aguilar-Pimentel, Antonio, Becker, Lore, Treise, Irina, Moreth, Kristin, Garrett, Lillian, Kistler, Martin, Hölter, Sabine M, Zimprich, Annemarie, Marschall, Susan, Amarie, Oana V, Calzada-Wack, Julia, Neff, Frauke, Brachthäuser, Laura, Lengger, Christoph, Stoeger, Claudia, Zapf, Lilly, Willershäuser, Monja, Cho, Yi-Li, da Silva-Buttkus, Patricia, Kraiger, Markus J, Mayer-Kuckuk, Philipp, Gampe, Karen Kristine, Wu, Moya, Conte, Nathalie, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Brommage, Robert, Relac, Mike, Matthews, Peter, Cater, Heather L, Natukunda, Helen P, Cleak, James, Teboul, Lydia M, Clementson-Mobbs, Sharon, Szoke-Kovacs, Zsombor, Walling, Alison P, Johnson, Sara J, Rozman, Jan [0000-0002-8035-8904], Kistler, Martin [0000-0003-0116-7761], Mason, Jeremy [0000-0002-2796-5123], Lelliott, Christopher J [0000-0001-8087-4530], Herault, Yann [0000-0001-7049-6900], Kent Lloyd, KC [0000-0002-5318-4144], McKerlie, Colin [0000-0002-2232-0967], Flicek, Paul [0000-0002-3897-7955], Maier, Holger [0000-0003-2514-8290], Fuchs, Helmut [0000-0002-5143-2677], Hrabe de Angelis, Martin [0000-0002-7898-2353], and Apollo - University of Cambridge Repository more...
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0301 basic medicine ,Blood Glucose ,Candidate gene ,Cancer Research ,Basal Metabolism/genetics ,Gene regulatory network ,Obesity/genetics ,genetics [Metabolic Diseases] ,General Physics and Astronomy ,Genome-wide association study ,Genome ,Mice ,genetics [Obesity] ,Triglycerides/metabolism ,2.1 Biological and endogenous factors ,Gene Regulatory Networks ,Aetiology ,lcsh:Science ,metabolism [Blood Glucose] ,Mice, Knockout ,Multidisciplinary ,genetics [Basal Metabolism] ,Phenotype ,Area Under Curve ,Diabetes Mellitus, Type 2/genetics ,ddc:500 ,Technology Platforms ,Type 2 ,metabolism [Triglycerides] ,Knockout ,Science ,Computational biology ,Biology ,genetics [Diabetes Mellitus, Type 2] ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Oxygen Consumption ,Metabolic Diseases ,Body Weight/genetics ,Diabetes Mellitus ,Genetics ,Animals ,Humans ,Metabolic Diseases/genetics ,Obesity ,Gene ,Gene knockout ,Triglycerides ,Oxygen Consumption/genetics ,Blood Glucose/metabolism ,genetics [Body Weight] ,Human Genome ,Body Weight ,Promoter ,General Chemistry ,genetics [Oxygen Consumption] ,High-Throughput Screening Assays ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,IMPC Consortium ,lcsh:Q ,Basal Metabolism ,Genome-Wide Association Study - Abstract
Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome., The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS. more...
- Published
- 2018
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