ALBERT

Description: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P 〈 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lango Allen, Hana -- Estrada, Karol -- Lettre, Guillaume -- Berndt, Sonja I -- Weedon, Michael N -- Rivadeneira, Fernando -- Willer, Cristen J -- Jackson, Anne U -- Vedantam, Sailaja -- Raychaudhuri, Soumya -- Ferreira, Teresa -- Wood, Andrew R -- Weyant, Robert J -- Segre, Ayellet V -- Speliotes, Elizabeth K -- Wheeler, Eleanor -- Soranzo, Nicole -- Park, Ju-Hyun -- Yang, Jian -- Gudbjartsson, Daniel -- Heard-Costa, Nancy L -- Randall, Joshua C -- Qi, Lu -- Vernon Smith, Albert -- Magi, Reedik -- Pastinen, Tomi -- Liang, Liming -- Heid, Iris M -- Luan, Jian'an -- Thorleifsson, Gudmar -- Winkler, Thomas W -- Goddard, Michael E -- Sin Lo, Ken -- Palmer, Cameron -- Workalemahu, Tsegaselassie -- Aulchenko, Yurii S -- Johansson, Asa -- Zillikens, M Carola -- Feitosa, Mary F -- Esko, Tonu -- Johnson, Toby -- Ketkar, Shamika -- Kraft, Peter -- Mangino, Massimo -- Prokopenko, Inga -- Absher, Devin -- Albrecht, Eva -- Ernst, Florian -- Glazer, Nicole L -- Hayward, Caroline -- Hottenga, Jouke-Jan -- Jacobs, Kevin B -- Knowles, Joshua W -- Kutalik, Zoltan -- Monda, Keri L -- Polasek, Ozren -- Preuss, Michael -- Rayner, Nigel W -- Robertson, Neil R -- Steinthorsdottir, Valgerdur -- Tyrer, Jonathan P -- Voight, Benjamin F -- Wiklund, Fredrik -- Xu, Jianfeng -- Zhao, Jing Hua -- Nyholt, Dale R -- Pellikka, Niina -- Perola, Markus -- Perry, John R B -- Surakka, Ida -- Tammesoo, Mari-Liis -- Altmaier, Elizabeth L -- Amin, Najaf -- Aspelund, Thor -- Bhangale, Tushar -- Boucher, Gabrielle -- Chasman, Daniel I -- Chen, Constance -- Coin, Lachlan -- Cooper, Matthew N -- Dixon, Anna L -- Gibson, Quince -- Grundberg, Elin -- Hao, Ke -- Juhani Junttila, M -- Kaplan, Lee M -- Kettunen, Johannes -- Konig, Inke R -- Kwan, Tony -- Lawrence, Robert W -- Levinson, Douglas F -- Lorentzon, Mattias -- McKnight, Barbara -- Morris, Andrew P -- Muller, Martina -- Suh Ngwa, Julius -- Purcell, Shaun -- Rafelt, Suzanne -- Salem, Rany M -- Salvi, Erika -- Sanna, Serena -- Shi, Jianxin -- Sovio, Ulla -- Thompson, John R -- Turchin, Michael C -- Vandenput, Liesbeth -- Verlaan, Dominique J -- Vitart, Veronique -- White, Charles C -- Ziegler, Andreas -- Almgren, Peter -- Balmforth, Anthony J -- Campbell, Harry -- Citterio, Lorena -- De Grandi, Alessandro -- Dominiczak, Anna -- Duan, Jubao -- Elliott, Paul -- Elosua, Roberto -- Eriksson, Johan G -- Freimer, Nelson B -- Geus, Eco J C -- Glorioso, Nicola -- Haiqing, Shen -- Hartikainen, Anna-Liisa -- Havulinna, Aki S -- Hicks, Andrew A -- Hui, Jennie -- Igl, Wilmar -- Illig, Thomas -- Jula, Antti -- Kajantie, Eero -- Kilpelainen, Tuomas O -- Koiranen, Markku -- Kolcic, Ivana -- Koskinen, Seppo -- Kovacs, Peter -- Laitinen, Jaana -- Liu, Jianjun -- Lokki, Marja-Liisa -- Marusic, Ana -- Maschio, Andrea -- Meitinger, Thomas -- Mulas, Antonella -- Pare, Guillaume -- Parker, Alex N -- Peden, John F -- Petersmann, Astrid -- Pichler, Irene -- Pietilainen, Kirsi H -- Pouta, Anneli -- Ridderstrale, Martin -- Rotter, Jerome I -- Sambrook, Jennifer G -- Sanders, Alan R -- Schmidt, Carsten Oliver -- Sinisalo, Juha -- Smit, Jan H -- Stringham, Heather M -- Bragi Walters, G -- Widen, Elisabeth -- Wild, Sarah H -- Willemsen, Gonneke -- Zagato, Laura -- Zgaga, Lina -- Zitting, Paavo -- Alavere, Helene -- Farrall, Martin -- McArdle, Wendy L -- Nelis, Mari -- Peters, Marjolein J -- Ripatti, Samuli -- van Meurs, Joyce B J -- Aben, Katja K -- Ardlie, Kristin G -- Beckmann, Jacques S -- Beilby, John P -- Bergman, Richard N -- Bergmann, Sven -- Collins, Francis S -- Cusi, Daniele -- den Heijer, Martin -- Eiriksdottir, Gudny -- Gejman, Pablo V -- Hall, Alistair S -- Hamsten, Anders -- Huikuri, Heikki V -- Iribarren, Carlos -- Kahonen, Mika -- Kaprio, Jaakko -- Kathiresan, Sekar -- Kiemeney, Lambertus -- Kocher, Thomas -- Launer, Lenore J -- Lehtimaki, Terho -- Melander, Olle -- Mosley, Tom H Jr -- Musk, Arthur W -- Nieminen, Markku S -- O'Donnell, Christopher J -- Ohlsson, Claes -- Oostra, Ben -- Palmer, Lyle J -- Raitakari, Olli -- Ridker, Paul M -- Rioux, John D -- Rissanen, Aila -- Rivolta, Carlo -- Schunkert, Heribert -- Shuldiner, Alan R -- Siscovick, David S -- Stumvoll, Michael -- Tonjes, Anke -- Tuomilehto, Jaakko -- van Ommen, Gert-Jan -- Viikari, Jorma -- Heath, Andrew C -- Martin, Nicholas G -- Montgomery, Grant W -- Province, Michael A -- Kayser, Manfred -- Arnold, Alice M -- Atwood, Larry D -- Boerwinkle, Eric -- Chanock, Stephen J -- Deloukas, Panos -- Gieger, Christian -- Gronberg, Henrik -- Hall, Per -- Hattersley, Andrew T -- Hengstenberg, Christian -- Hoffman, Wolfgang -- Lathrop, G Mark -- Salomaa, Veikko -- Schreiber, Stefan -- Uda, Manuela -- Waterworth, Dawn -- Wright, Alan F -- Assimes, Themistocles L -- Barroso, Ines -- Hofman, Albert -- Mohlke, Karen L -- Boomsma, Dorret I -- Caulfield, Mark J -- Cupples, L Adrienne -- Erdmann, Jeanette -- Fox, Caroline S -- Gudnason, Vilmundur -- Gyllensten, Ulf -- Harris, Tamara B -- Hayes, Richard B -- Jarvelin, Marjo-Riitta -- Mooser, Vincent -- Munroe, Patricia B -- Ouwehand, Willem H -- Penninx, Brenda W -- Pramstaller, Peter P -- Quertermous, Thomas -- Rudan, Igor -- Samani, Nilesh J -- Spector, Timothy D -- Volzke, Henry -- Watkins, Hugh -- Wilson, James F -- Groop, Leif C -- Haritunians, Talin -- Hu, Frank B -- Kaplan, Robert C -- Metspalu, Andres -- North, Kari E -- Schlessinger, David -- Wareham, Nicholas J -- Hunter, David J -- O'Connell, Jeffrey R -- Strachan, David P -- Wichmann, H-Erich -- Borecki, Ingrid B -- van Duijn, Cornelia M -- Schadt, Eric E -- Thorsteinsdottir, Unnur -- Peltonen, Leena -- Uitterlinden, Andre G -- Visscher, Peter M -- Chatterjee, Nilanjan -- Loos, Ruth J F -- Boehnke, Michael -- McCarthy, Mark I -- Ingelsson, Erik -- Lindgren, Cecilia M -- Abecasis, Goncalo R -- Stefansson, Kari -- Frayling, Timothy M -- Hirschhorn, Joel N -- 064890/Wellcome Trust/United Kingdom -- 068545/Wellcome Trust/United Kingdom -- 068545/Z/02/Wellcome Trust/United Kingdom -- 072856/Wellcome Trust/United Kingdom -- 072960/Wellcome Trust/United Kingdom -- 075491/Wellcome Trust/United Kingdom -- 076113/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 076113/C/04/Z/Wellcome Trust/United Kingdom -- 077016/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079557/Wellcome Trust/United Kingdom -- 079771/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 081682/Wellcome Trust/United Kingdom -- 081682/Z/06/Z/Wellcome Trust/United Kingdom -- 083270/Wellcome Trust/United Kingdom -- 084183/Z/07/Z/Wellcome Trust/United Kingdom -- 085301/Wellcome Trust/United Kingdom -- 085301/Z/08/Z/Wellcome Trust/United Kingdom -- 086596/Wellcome Trust/United Kingdom -- 086596/Z/08/Z/Wellcome Trust/United Kingdom -- 088885/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 091746/Wellcome Trust/United Kingdom -- 091746/Z/10/Z/Wellcome Trust/United Kingdom -- 263-MA-410953/PHS HHS/ -- AA014041/AA/NIAAA NIH HHS/ -- AA07535/AA/NIAAA NIH HHS/ -- AA10248/AA/NIAAA NIH HHS/ -- AA13320/AA/NIAAA NIH HHS/ -- AA13321/AA/NIAAA NIH HHS/ -- AA13326/AA/NIAAA NIH HHS/ -- CA047988/CA/NCI NIH HHS/ -- CA49449/CA/NCI NIH HHS/ -- CA50385/CA/NCI NIH HHS/ -- CA65725/CA/NCI NIH HHS/ -- CA67262/CA/NCI NIH HHS/ -- CA87969/CA/NCI NIH HHS/ -- CZB/4/276/Chief Scientist Office/United Kingdom -- 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GM074518-05/GM/NIGMS NIH HHS/ -- U01 HG004399/HG/NHGRI NIH HHS/ -- U01 HG004399-02/HG/NHGRI NIH HHS/ -- U01 HG004402/HG/NHGRI NIH HHS/ -- U01 HG004402-02/HG/NHGRI NIH HHS/ -- U01 HG005214/HG/NHGRI NIH HHS/ -- U01 HG005214-02/HG/NHGRI NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL069757-10/HL/NHLBI NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL080295-04/HL/NHLBI NIH HHS/ -- U01 HL084729/HL/NHLBI NIH HHS/ -- U01 HL084729-03/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 HL084756-03/HL/NHLBI NIH HHS/ -- U01 MH079469/MH/NIMH NIH HHS/ -- U01 MH079469-03/MH/NIMH NIH HHS/ -- U01 MH079470/MH/NIMH NIH HHS/ -- U01 MH079470-03/MH/NIMH NIH HHS/ -- U01-CA098233/CA/NCI NIH HHS/ -- U01-GM074518/GM/NIGMS NIH HHS/ -- U01-HG004399/HG/NHGRI NIH HHS/ -- U01-HG004402/HG/NHGRI NIH HHS/ -- U01-HL080295/HL/NHLBI NIH HHS/ -- U01-HL084756/HL/NHLBI NIH HHS/ -- U01-HL72515/HL/NHLBI NIH HHS/ -- U01-MH79469/MH/NIMH NIH HHS/ -- U01-MH79470/MH/NIMH NIH HHS/ -- U54-RR020278/RR/NCRR NIH HHS/ -- UL1-RR025005/RR/NCRR NIH HHS/ -- Z01-AG00675/AG/NIA NIH HHS/ -- Z01-AG007380/AG/NIA NIH HHS/ -- Z01-HG000024/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2010 Oct 14;467(7317):832-8. doi: 10.1038/nature09410. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881960" target="_blank"〉PubMed〈/a〉

Description: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902243/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902243/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Cancer Genome Consortium -- Hudson, Thomas J -- Anderson, Warwick -- Artez, Axel -- Barker, Anna D -- Bell, Cindy -- Bernabe, Rosa R -- Bhan, M K -- Calvo, Fabien -- Eerola, Iiro -- Gerhard, Daniela S -- Guttmacher, Alan -- Guyer, Mark -- Hemsley, Fiona M -- Jennings, Jennifer L -- Kerr, David -- Klatt, Peter -- Kolar, Patrik -- Kusada, Jun -- Lane, David P -- Laplace, Frank -- Youyong, Lu -- Nettekoven, Gerd -- Ozenberger, Brad -- Peterson, Jane -- Rao, T S -- Remacle, Jacques -- Schafer, Alan J -- Shibata, Tatsuhiro -- Stratton, Michael R -- Vockley, Joseph G -- Watanabe, Koichi -- Yang, Huanming -- Yuen, Matthew M F -- Knoppers, Bartha M -- Bobrow, Martin -- Cambon-Thomsen, Anne -- Dressler, Lynn G -- Dyke, Stephanie O M -- Joly, Yann -- Kato, Kazuto -- Kennedy, Karen L -- Nicolas, Pilar -- Parker, Michael J -- Rial-Sebbag, Emmanuelle -- Romeo-Casabona, Carlos M -- Shaw, Kenna M -- Wallace, Susan -- Wiesner, Georgia L -- Zeps, Nikolajs -- Lichter, Peter -- Biankin, Andrew V -- Chabannon, Christian -- Chin, Lynda -- Clement, Bruno -- de Alava, Enrique -- Degos, Francoise -- Ferguson, Martin L -- Geary, Peter -- Hayes, D Neil -- Johns, Amber L -- Kasprzyk, Arek -- Nakagawa, Hidewaki -- Penny, Robert -- Piris, Miguel A -- Sarin, Rajiv -- Scarpa, Aldo -- van de Vijver, Marc -- Futreal, P Andrew -- Aburatani, Hiroyuki -- Bayes, Monica -- Botwell, David D L -- Campbell, Peter J -- Estivill, Xavier -- Grimmond, Sean M -- Gut, Ivo -- Hirst, Martin -- Lopez-Otin, Carlos -- Majumder, Partha -- Marra, Marco -- McPherson, John D -- Ning, Zemin -- Puente, Xose S -- Ruan, Yijun -- Stunnenberg, Hendrik G -- Swerdlow, Harold -- Velculescu, Victor E -- Wilson, Richard K -- Xue, Hong H -- Yang, Liu -- Spellman, Paul T -- Bader, Gary D -- Boutros, Paul C -- Flicek, Paul -- Getz, Gad -- Guigo, Roderic -- Guo, Guangwu -- Haussler, David -- Heath, Simon -- Hubbard, Tim J -- Jiang, Tao -- Jones, Steven M -- Li, Qibin -- Lopez-Bigas, Nuria -- Luo, Ruibang -- Muthuswamy, Lakshmi -- Ouellette, B F Francis -- Pearson, John V -- Quesada, Victor -- Raphael, Benjamin J -- Sander, Chris -- Speed, Terence P -- Stein, Lincoln D -- Stuart, Joshua M -- Teague, Jon W -- Totoki, Yasushi -- Tsunoda, Tatsuhiko -- Valencia, Alfonso -- Wheeler, David A -- Wu, Honglong -- Zhao, Shancen -- Zhou, Guangyu -- Lathrop, Mark -- Thomas, Gilles -- Yoshida, Teruhiko -- Axton, Myles -- Gunter, Chris -- Miller, Linda J -- Zhang, Junjun -- Haider, Syed A -- Wang, Jianxin -- Yung, Christina K -- Cros, Anthony -- Liang, Yong -- Gnaneshan, Saravanamuttu -- Guberman, Jonathan -- Hsu, Jack -- Chalmers, Don R C -- Hasel, Karl W -- Kaan, Terry S H -- Lowrance, William W -- Masui, Tohru -- Rodriguez, Laura Lyman -- Vergely, Catherine -- Bowtell, David D L -- Cloonan, Nicole -- deFazio, Anna -- Eshleman, James R -- Etemadmoghadam, Dariush -- Gardiner, Brooke B -- Kench, James G -- Sutherland, Robert L -- Tempero, Margaret A -- Waddell, Nicola J -- Wilson, Peter J -- Gallinger, Steve -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Mukhopadhyay, Debabrata -- DePinho, Ronald A -- Thayer, Sarah -- Shazand, Kamran -- Beck, Timothy -- Sam, Michelle -- Timms, Lee -- Ballin, Vanessa -- Lu, Youyong -- Ji, Jiafu -- Zhang, Xiuqing -- Chen, Feng -- Hu, Xueda -- Yang, Qi -- Tian, Geng -- Zhang, Lianhai -- Xing, Xiaofang -- Li, Xianghong -- Zhu, Zhenggang -- Yu, Yingyan -- Yu, Jun -- Tost, Jorg -- Brennan, Paul -- Holcatova, Ivana -- Zaridze, David -- Brazma, Alvis -- Egevard, Lars -- Prokhortchouk, Egor -- Banks, Rosamonde Elizabeth -- Uhlen, Mathias -- Viksna, Juris -- Ponten, Fredrik -- Skryabin, Konstantin -- Birney, Ewan -- Borg, Ake -- Borresen-Dale, Anne-Lise -- Caldas, Carlos -- Foekens, John A -- Martin, Sancha -- Reis-Filho, Jorge S -- Richardson, Andrea L -- Sotiriou, Christos -- Thoms, Giles -- van't Veer, Laura -- Birnbaum, Daniel -- Blanche, Helene -- Boucher, Pascal -- Boyault, Sandrine -- Masson-Jacquemier, Jocelyne D -- Pauporte, Iris -- Pivot, Xavier -- Vincent-Salomon, Anne -- Tabone, Eric -- Theillet, Charles -- Treilleux, Isabelle -- Bioulac-Sage, Paulette -- Decaens, Thomas -- Franco, Dominique -- Gut, Marta -- Samuel, Didier -- Zucman-Rossi, Jessica -- Eils, Roland -- Brors, Benedikt -- Korbel, Jan O -- Korshunov, Andrey -- Landgraf, Pablo -- Lehrach, Hans -- Pfister, Stefan -- Radlwimmer, Bernhard -- Reifenberger, Guido -- Taylor, Michael D -- von Kalle, Christof -- Majumder, Partha P -- Pederzoli, Paolo -- Lawlor, Rita A -- Delledonne, Massimo -- Bardelli, Alberto -- Gress, Thomas -- Klimstra, David -- Zamboni, Giuseppe -- Nakamura, Yusuke -- Miyano, Satoru -- Fujimoto, Akihiro -- Campo, Elias -- de Sanjose, Silvia -- Montserrat, Emili -- Gonzalez-Diaz, Marcos -- Jares, Pedro -- Himmelbauer, Heinz -- Bea, Silvia -- Aparicio, Samuel -- Easton, Douglas F -- Collins, Francis S -- Compton, Carolyn C -- Lander, Eric S -- Burke, Wylie -- Green, Anthony R -- Hamilton, Stanley R -- Kallioniemi, Olli P -- Ley, Timothy J -- Liu, Edison T -- Wainwright, Brandon J -- 077198/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- 6613/Cancer Research UK/United Kingdom -- K08 DK071329/DK/NIDDK NIH HHS/ -- K08 DK071329-04/DK/NIDDK NIH HHS/ -- K08 DK071329-05/DK/NIDDK NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- P01 CA117969-04S1/CA/NCI NIH HHS/ -- P01 CA117969-05/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50 CA102701-08/CA/NCI NIH HHS/ -- P50 CA127003/CA/NCI NIH HHS/ -- P50 CA127003-04/CA/NCI NIH HHS/ -- P50 CA127003-05/CA/NCI NIH HHS/ -- R01 HG001806-02/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):993-8. doi: 10.1038/nature08987.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393554" target="_blank"〉PubMed〈/a〉

Description: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in 〉100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P 〈 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teslovich, Tanya M -- Musunuru, Kiran -- Smith, Albert V -- Edmondson, Andrew C -- Stylianou, Ioannis M -- Koseki, Masahiro -- Pirruccello, James P -- Ripatti, Samuli -- Chasman, Daniel I -- Willer, Cristen J -- Johansen, Christopher T -- Fouchier, Sigrid W -- Isaacs, Aaron -- Peloso, Gina M -- Barbalic, Maja -- Ricketts, Sally L -- Bis, Joshua C -- Aulchenko, Yurii S -- Thorleifsson, Gudmar -- Feitosa, Mary F -- Chambers, John -- Orho-Melander, Marju -- Melander, Olle -- Johnson, Toby -- Li, Xiaohui -- Guo, Xiuqing -- Li, Mingyao -- Shin Cho, Yoon -- Jin Go, Min -- Jin Kim, Young -- Lee, Jong-Young -- Park, Taesung -- Kim, Kyunga -- Sim, Xueling -- Twee-Hee Ong, Rick -- Croteau-Chonka, Damien C -- Lange, Leslie A -- Smith, Joshua D -- Song, Kijoung -- Hua Zhao, Jing -- Yuan, Xin -- Luan, Jian'an -- Lamina, Claudia -- Ziegler, Andreas -- Zhang, Weihua -- Zee, Robert Y L -- Wright, Alan F -- Witteman, Jacqueline C M -- Wilson, James F -- Willemsen, Gonneke -- Wichmann, H-Erich -- Whitfield, John B -- Waterworth, Dawn M -- Wareham, Nicholas J -- Waeber, Gerard -- Vollenweider, Peter -- Voight, Benjamin F -- Vitart, Veronique -- Uitterlinden, Andre G -- Uda, Manuela -- Tuomilehto, Jaakko -- Thompson, John R -- Tanaka, Toshiko -- Surakka, Ida -- Stringham, Heather M -- Spector, Tim D -- Soranzo, Nicole -- Smit, Johannes H -- Sinisalo, Juha -- Silander, Kaisa -- Sijbrands, Eric J G -- Scuteri, Angelo -- Scott, James -- Schlessinger, David -- Sanna, Serena -- Salomaa, Veikko -- Saharinen, Juha -- Sabatti, Chiara -- Ruokonen, Aimo -- Rudan, Igor -- Rose, Lynda M -- Roberts, Robert -- Rieder, Mark -- Psaty, Bruce M -- Pramstaller, Peter P -- Pichler, Irene -- Perola, Markus -- Penninx, Brenda W J H -- Pedersen, Nancy L -- Pattaro, Cristian -- Parker, Alex N -- Pare, Guillaume -- Oostra, Ben A -- O'Donnell, Christopher J -- Nieminen, Markku S -- Nickerson, Deborah A -- Montgomery, Grant W -- Meitinger, Thomas -- McPherson, Ruth -- McCarthy, Mark I -- McArdle, Wendy -- Masson, David -- Martin, Nicholas G -- Marroni, Fabio -- Mangino, Massimo -- Magnusson, Patrik K E -- Lucas, Gavin -- Luben, Robert -- Loos, Ruth J F -- Lokki, Marja-Liisa -- Lettre, Guillaume -- Langenberg, Claudia -- Launer, Lenore J -- Lakatta, Edward G -- Laaksonen, Reijo -- Kyvik, Kirsten O -- Kronenberg, Florian -- Konig, Inke R -- Khaw, Kay-Tee -- Kaprio, Jaakko -- Kaplan, Lee M -- Johansson, Asa -- Jarvelin, Marjo-Riitta -- Janssens, A Cecile J W -- Ingelsson, Erik -- Igl, Wilmar -- Kees Hovingh, G -- Hottenga, Jouke-Jan -- Hofman, Albert -- Hicks, Andrew A -- Hengstenberg, Christian -- Heid, Iris M -- Hayward, Caroline -- Havulinna, Aki S -- Hastie, Nicholas D -- Harris, Tamara B -- Haritunians, Talin -- Hall, Alistair S -- Gyllensten, Ulf -- Guiducci, Candace -- Groop, Leif C -- Gonzalez, Elena -- Gieger, Christian -- Freimer, Nelson B -- Ferrucci, Luigi -- Erdmann, Jeanette -- Elliott, Paul -- Ejebe, Kenechi G -- Doring, Angela -- Dominiczak, Anna F -- Demissie, Serkalem -- Deloukas, Panagiotis -- de Geus, Eco J C -- de Faire, Ulf -- Crawford, Gabriel -- Collins, Francis S -- Chen, Yii-der I -- Caulfield, Mark J -- Campbell, Harry -- Burtt, Noel P -- Bonnycastle, Lori L -- Boomsma, Dorret I -- Boekholdt, S Matthijs -- Bergman, Richard N -- Barroso, Ines -- Bandinelli, Stefania -- Ballantyne, Christie M -- Assimes, Themistocles L -- Quertermous, Thomas -- Altshuler, David -- Seielstad, Mark -- Wong, Tien Y -- Tai, E-Shyong -- Feranil, Alan B -- Kuzawa, Christopher W -- Adair, Linda S -- Taylor, Herman A Jr -- Borecki, Ingrid B -- Gabriel, Stacey B -- Wilson, James G -- Holm, Hilma -- Thorsteinsdottir, Unnur -- Gudnason, Vilmundur -- Krauss, Ronald M -- Mohlke, Karen L -- Ordovas, Jose M -- Munroe, Patricia B -- Kooner, Jaspal S -- Tall, Alan R -- Hegele, Robert A -- Kastelein, John J P -- Schadt, Eric E -- Rotter, Jerome I -- Boerwinkle, Eric -- Strachan, David P -- Mooser, Vincent -- Stefansson, Kari -- Reilly, Muredach P -- Samani, Nilesh J -- Schunkert, Heribert -- Cupples, L Adrienne -- Sandhu, Manjinder S -- Ridker, Paul M -- Rader, Daniel J -- van Duijn, Cornelia M -- Peltonen, Leena -- Abecasis, Goncalo R -- Boehnke, Michael -- Kathiresan, Sekar -- 068545/Z/02/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 1Z01 HG000024/HG/NHGRI NIH HHS/ -- 5R01DK06833603/DK/NIDDK NIH HHS/ -- 5R01DK07568102/DK/NIDDK NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01HL08770003/HL/NHLBI NIH HHS/ -- 5R01HL08821502/HL/NHLBI NIH HHS/ -- CA 047988/CA/NCI NIH HHS/ -- CZB/4/710/Chief Scientist Office/United Kingdom -- DK062370/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK072193/DK/NIDDK NIH HHS/ -- DK078150/DK/NIDDK NIH HHS/ -- DK56350/DK/NIDDK NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- G0000934/Medical Research Council/United Kingdom -- G0401527/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G0801566/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HHSN268200625226C/PHS HHS/ -- HL 04381/HL/NHLBI NIH HHS/ -- HL 080467/HL/NHLBI NIH HHS/ -- HL-54776/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- K99 HL098364/HL/NHLBI NIH HHS/ -- K99 HL098364-01/HL/NHLBI NIH HHS/ -- K99HL094535/HL/NHLBI NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_QA137934/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HG-65403/HG/NHGRI NIH HHS/ -- N02-HL-6-4278/HL/NHLBI NIH HHS/ -- PG/02/128/British Heart Foundation/United Kingdom -- PG/08/094/British Heart Foundation/United Kingdom -- PG/08/094/26019/British Heart Foundation/United Kingdom -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087676/HL/NHLBI NIH HHS/ -- R01 HL089650/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL087652/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R24 HD050924/HD/NICHD NIH HHS/ -- RC1 HL099634/HL/NHLBI NIH HHS/ -- RC1 HL099634-02/HL/NHLBI NIH HHS/ -- RC1 HL099793/HL/NHLBI NIH HHS/ -- RC2 HL101864,/HL/NHLBI NIH HHS/ -- RC2 HL102419/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RR20649/RR/NCRR NIH HHS/ -- SP/08/005/25115/British Heart Foundation/United Kingdom -- T32 GM007092/GM/NIGMS NIH HHS/ -- T32 HG00040/HG/NHGRI NIH HHS/ -- T32HL007208/HL/NHLBI NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):707-13. doi: 10.1038/nature09270.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686565" target="_blank"〉PubMed〈/a〉

Description: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (〈1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021798/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021798/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinto, Dalila -- Pagnamenta, Alistair T -- Klei, Lambertus -- Anney, Richard -- Merico, Daniele -- Regan, Regina -- Conroy, Judith -- Magalhaes, Tiago R -- Correia, Catarina -- Abrahams, Brett S -- Almeida, Joana -- Bacchelli, Elena -- Bader, Gary D -- Bailey, Anthony J -- Baird, Gillian -- Battaglia, Agatino -- Berney, Tom -- Bolshakova, Nadia -- Bolte, Sven -- Bolton, Patrick F -- Bourgeron, Thomas -- Brennan, Sean -- Brian, Jessica -- Bryson, Susan E -- Carson, Andrew R -- Casallo, Guillermo -- Casey, Jillian -- Chung, Brian H Y -- Cochrane, Lynne -- Corsello, Christina -- Crawford, Emily L -- Crossett, Andrew -- Cytrynbaum, Cheryl -- Dawson, Geraldine -- de Jonge, Maretha -- Delorme, Richard -- Drmic, Irene -- Duketis, Eftichia -- Duque, Frederico -- Estes, Annette -- Farrar, Penny -- Fernandez, Bridget A -- Folstein, Susan E -- Fombonne, Eric -- Freitag, Christine M -- Gilbert, John -- Gillberg, Christopher -- Glessner, Joseph T -- Goldberg, Jeremy -- Green, Andrew -- Green, Jonathan -- Guter, Stephen J -- Hakonarson, Hakon -- Heron, Elizabeth A -- Hill, Matthew -- Holt, Richard -- Howe, Jennifer L -- Hughes, Gillian -- Hus, Vanessa -- Igliozzi, Roberta -- Kim, Cecilia -- Klauck, Sabine M -- Kolevzon, Alexander -- Korvatska, Olena -- Kustanovich, Vlad -- Lajonchere, Clara M -- Lamb, Janine A -- Laskawiec, Magdalena -- Leboyer, Marion -- Le Couteur, Ann -- Leventhal, Bennett L -- Lionel, Anath C -- Liu, Xiao-Qing -- Lord, Catherine -- Lotspeich, Linda -- Lund, Sabata C -- Maestrini, Elena -- Mahoney, William -- Mantoulan, Carine -- Marshall, Christian R -- McConachie, Helen -- McDougle, Christopher J -- McGrath, Jane -- McMahon, William M -- Merikangas, Alison -- Migita, Ohsuke -- Minshew, Nancy J -- Mirza, Ghazala K -- Munson, Jeff -- Nelson, Stanley F -- Noakes, Carolyn -- Noor, Abdul -- Nygren, Gudrun -- Oliveira, Guiomar -- Papanikolaou, Katerina -- Parr, Jeremy R -- Parrini, Barbara -- Paton, Tara -- Pickles, Andrew -- Pilorge, Marion -- Piven, Joseph -- Ponting, Chris P -- Posey, David J -- Poustka, Annemarie -- Poustka, Fritz -- Prasad, Aparna -- Ragoussis, Jiannis -- Renshaw, Katy -- Rickaby, Jessica -- Roberts, Wendy -- Roeder, Kathryn -- Roge, Bernadette -- Rutter, Michael L -- Bierut, Laura J -- Rice, John P -- Salt, Jeff -- Sansom, Katherine -- Sato, Daisuke -- Segurado, Ricardo -- Sequeira, Ana F -- Senman, Lili -- Shah, Naisha -- Sheffield, Val C -- Soorya, Latha -- Sousa, Ines -- Stein, Olaf -- Sykes, Nuala -- Stoppioni, Vera -- Strawbridge, Christina -- Tancredi, Raffaella -- Tansey, Katherine -- Thiruvahindrapduram, Bhooma -- Thompson, Ann P -- Thomson, Susanne -- Tryfon, Ana -- Tsiantis, John -- Van Engeland, Herman -- Vincent, John B -- Volkmar, Fred -- Wallace, Simon -- Wang, Kai -- Wang, Zhouzhi -- Wassink, Thomas H -- Webber, Caleb -- Weksberg, Rosanna -- Wing, Kirsty -- Wittemeyer, Kerstin -- Wood, Shawn -- Wu, Jing -- Yaspan, Brian L -- Zurawiecki, Danielle -- Zwaigenbaum, Lonnie -- Buxbaum, Joseph D -- Cantor, Rita M -- Cook, Edwin H -- Coon, Hilary -- Cuccaro, Michael L -- Devlin, Bernie -- Ennis, Sean -- Gallagher, Louise -- Geschwind, Daniel H -- Gill, Michael -- Haines, Jonathan L -- Hallmayer, Joachim -- Miller, Judith -- Monaco, Anthony P -- Nurnberger, John I Jr -- Paterson, Andrew D -- Pericak-Vance, Margaret A -- Schellenberg, Gerard D -- Szatmari, Peter -- Vicente, Astrid M -- Vieland, Veronica J -- Wijsman, Ellen M -- Scherer, Stephen W -- Sutcliffe, James S -- Betancur, Catalina -- 075491/Z/04/Wellcome Trust/United Kingdom -- AS2077/Autism Speaks/ -- AS7462/Autism Speaks/ -- G0601030/Medical Research Council/United Kingdom -- HD055751/HD/NICHD NIH HHS/ -- HD055782/HD/NICHD NIH HHS/ -- HD055784/HD/NICHD NIH HHS/ -- HD35465/HD/NICHD NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- MH061009/MH/NIMH NIH HHS/ -- MH06359/MH/NIMH NIH HHS/ -- MH066673/MH/NIMH NIH HHS/ -- MH080647/MH/NIMH NIH HHS/ -- MH081754/MH/NIMH NIH HHS/ -- MH52708/MH/NIMH NIH HHS/ -- MH55284/MH/NIMH NIH HHS/ -- MH57881/MH/NIMH NIH HHS/ -- MH66766/MH/NIMH NIH HHS/ -- NS026630/NS/NINDS NIH HHS/ -- NS042165/NS/NINDS NIH HHS/ -- NS049261/NS/NINDS NIH HHS/ -- P01 CA089392/CA/NCI NIH HHS/ -- P01 CA089392-08/CA/NCI NIH HHS/ -- P01 HD035465-01S1/HD/NICHD NIH HHS/ -- P01 NS026630/NS/NINDS NIH HHS/ -- P01 NS026630-15/NS/NINDS NIH HHS/ -- P50 HD055748/HD/NICHD NIH HHS/ -- P50 HD055748-01/HD/NICHD NIH HHS/ -- P50 HD055748-02/HD/NICHD NIH HHS/ -- P50 HD055748-03/HD/NICHD NIH HHS/ -- P50 HD055751/HD/NICHD NIH HHS/ -- P50 HD055751-01/HD/NICHD NIH HHS/ -- P50 HD055782/HD/NICHD NIH HHS/ -- P50 HD055782-04/HD/NICHD NIH HHS/ -- R01 DA013423/DA/NIDA NIH HHS/ -- R01 DA013423-05/DA/NIDA NIH HHS/ -- R01 DA019963/DA/NIDA NIH HHS/ -- R01 DA019963-01A2/DA/NIDA NIH HHS/ -- R01 DA019963-02/DA/NIDA NIH HHS/ -- R01 DA019963-03/DA/NIDA NIH HHS/ -- R01 MH052708-05/MH/NIMH NIH HHS/ -- R01 MH055284/MH/NIMH NIH HHS/ -- R01 MH055284-04/MH/NIMH NIH HHS/ -- R01 MH057881/MH/NIMH NIH HHS/ -- R01 MH057881-02/MH/NIMH NIH HHS/ -- R01 MH061009/MH/NIMH NIH HHS/ -- R01 MH061009-05/MH/NIMH NIH HHS/ -- R01 MH080647/MH/NIMH NIH HHS/ -- R01 MH080647-11/MH/NIMH NIH HHS/ -- R01 MH081754/MH/NIMH NIH HHS/ -- R01 MH081754-01/MH/NIMH NIH HHS/ -- R01 NS042165/NS/NINDS NIH HHS/ -- R01 NS042165-05/NS/NINDS NIH HHS/ -- R01 NS049261/NS/NINDS NIH HHS/ -- R01 NS049261-02/NS/NINDS NIH HHS/ -- U01 HG004422/HG/NHGRI NIH HHS/ -- U01 HG004422-02/HG/NHGRI NIH HHS/ -- U10 MH066766-05/MH/NIMH NIH HHS/ -- U19 HD035469/HD/NICHD NIH HHS/ -- U19 HD035469-06/HD/NICHD NIH HHS/ -- U19 HD035469-07/HD/NICHD NIH HHS/ -- U19 HD035469-08/HD/NICHD NIH HHS/ -- U19 HD035469-09/HD/NICHD NIH HHS/ -- U19 HD035469-10/HD/NICHD NIH HHS/ -- U54 MH066673/MH/NIMH NIH HHS/ -- U54 MH066673-05/MH/NIMH NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Jul 15;466(7304):368-72. doi: 10.1038/nature09146. Epub 2010 Jun 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20531469" target="_blank"〉PubMed〈/a〉

Description: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892339/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892339/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wellcome Trust Case Control Consortium -- Craddock, Nick -- Hurles, Matthew E -- Cardin, Niall -- Pearson, Richard D -- Plagnol, Vincent -- Robson, Samuel -- Vukcevic, Damjan -- Barnes, Chris -- Conrad, Donald F -- Giannoulatou, Eleni -- Holmes, Chris -- Marchini, Jonathan L -- Stirrups, Kathy -- Tobin, Martin D -- Wain, Louise V -- Yau, Chris -- Aerts, Jan -- Ahmad, Tariq -- Andrews, T Daniel -- Arbury, Hazel -- Attwood, Anthony -- Auton, Adam -- Ball, Stephen G -- Balmforth, Anthony J -- Barrett, Jeffrey C -- Barroso, Ines -- Barton, Anne -- Bennett, Amanda J -- Bhaskar, Sanjeev -- Blaszczyk, Katarzyna -- Bowes, John -- Brand, Oliver J -- Braund, Peter S -- Bredin, Francesca -- Breen, Gerome -- Brown, Morris J -- Bruce, Ian N -- Bull, Jaswinder -- Burren, Oliver S -- Burton, John -- Byrnes, Jake -- Caesar, Sian -- Clee, Chris M -- Coffey, Alison J -- Connell, John M C -- Cooper, Jason D -- Dominiczak, Anna F -- Downes, Kate -- Drummond, Hazel E -- Dudakia, Darshna -- Dunham, Andrew -- Ebbs, Bernadette -- Eccles, Diana -- Edkins, Sarah -- Edwards, Cathryn -- Elliot, Anna -- Emery, Paul -- Evans, David M -- Evans, Gareth -- Eyre, Steve -- Farmer, Anne -- Ferrier, I Nicol -- Feuk, Lars -- Fitzgerald, Tomas -- Flynn, Edward -- Forbes, Alistair -- Forty, Liz -- Franklyn, Jayne A -- Freathy, Rachel M -- Gibbs, Polly -- Gilbert, Paul -- Gokumen, Omer -- Gordon-Smith, Katherine -- Gray, Emma -- Green, Elaine -- Groves, Chris J -- Grozeva, Detelina -- Gwilliam, Rhian -- Hall, Anita -- Hammond, Naomi -- Hardy, Matt -- Harrison, Pile -- Hassanali, Neelam -- Hebaishi, Husam -- Hines, Sarah -- Hinks, Anne -- Hitman, Graham A -- Hocking, Lynne -- Howard, Eleanor -- Howard, Philip -- Howson, Joanna M M -- Hughes, Debbie -- Hunt, Sarah -- Isaacs, John D -- Jain, Mahim -- Jewell, Derek P -- Johnson, Toby -- Jolley, Jennifer D -- Jones, Ian R -- Jones, Lisa A -- Kirov, George -- Langford, Cordelia F -- Lango-Allen, Hana -- Lathrop, G Mark -- Lee, James -- Lee, Kate L -- Lees, Charlie -- Lewis, Kevin -- Lindgren, Cecilia M -- Maisuria-Armer, Meeta -- Maller, Julian -- Mansfield, John -- Martin, Paul -- Massey, Dunecan C O -- McArdle, Wendy L -- McGuffin, Peter -- McLay, Kirsten E -- Mentzer, Alex -- Mimmack, Michael L -- Morgan, Ann E -- Morris, Andrew P -- Mowat, Craig -- Myers, Simon -- Newman, William -- Nimmo, Elaine R -- O'Donovan, Michael C -- Onipinla, Abiodun -- Onyiah, Ifejinelo -- Ovington, Nigel R -- Owen, Michael J -- Palin, Kimmo -- Parnell, Kirstie -- Pernet, David -- Perry, John R B -- Phillips, Anne -- Pinto, Dalila -- Prescott, Natalie J -- Prokopenko, Inga -- Quail, Michael A -- Rafelt, Suzanne -- Rayner, Nigel W -- Redon, Richard -- Reid, David M -- Renwick -- Ring, Susan M -- Robertson, Neil -- Russell, Ellie -- St Clair, David -- Sambrook, Jennifer G -- Sanderson, Jeremy D -- Schuilenburg, Helen -- Scott, Carol E -- Scott, Richard -- Seal, Sheila -- Shaw-Hawkins, Sue -- Shields, Beverley M -- Simmonds, Matthew J -- Smyth, Debbie J -- Somaskantharajah, Elilan -- Spanova, Katarina -- Steer, Sophia -- Stephens, Jonathan -- Stevens, Helen E -- Stone, Millicent A -- Su, Zhan -- Symmons, Deborah P M -- Thompson, John R -- Thomson, Wendy -- Travers, Mary E -- Turnbull, Clare -- Valsesia, Armand -- Walker, Mark -- Walker, Neil M -- Wallace, Chris -- Warren-Perry, Margaret -- Watkins, Nicholas A -- Webster, John -- Weedon, Michael N -- Wilson, Anthony G -- Woodburn, Matthew -- Wordsworth, B Paul -- Young, Allan H -- Zeggini, Eleftheria -- Carter, Nigel P -- Frayling, Timothy M -- Lee, Charles -- McVean, Gil -- Munroe, Patricia B -- Palotie, Aarno -- Sawcer, Stephen J -- Scherer, Stephen W -- Strachan, David P -- Tyler-Smith, Chris -- Brown, Matthew A -- Burton, Paul R -- Caulfield, Mark J -- Compston, Alastair -- Farrall, Martin -- Gough, Stephen C L -- Hall, Alistair S -- Hattersley, Andrew T -- Hill, Adrian V S -- Mathew, Christopher G -- Pembrey, Marcus -- Satsangi, Jack -- Stratton, Michael R -- Worthington, Jane -- Deloukas, Panos -- Duncanson, Audrey -- Kwiatkowski, Dominic P -- McCarthy, Mark I -- Ouwehand, Willem -- Parkes, Miles -- Rahman, Nazneen -- Todd, John A -- Samani, Nilesh J -- Donnelly, Peter -- 061858/Wellcome Trust/United Kingdom -- 083948/Wellcome Trust/United Kingdom -- 089989/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 17552/Arthritis Research UK/United Kingdom -- CZB/4/540/Chief Scientist Office/United Kingdom -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- G0400874/Medical Research Council/United Kingdom -- G0500115/Medical Research Council/United Kingdom -- G0501942/Medical Research Council/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0700491/Medical Research Council/United Kingdom -- G0701003/Medical Research Council/United Kingdom -- G0701420/Medical Research Council/United Kingdom -- G0701810/Medical Research Council/United Kingdom -- G0701810(85517)/Medical Research Council/United Kingdom -- G0800383/Medical Research Council/United Kingdom -- G0800509/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G19/9/Medical Research Council/United Kingdom -- G90/106/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- MC_UP_A390_1107/Medical Research Council/United Kingdom -- RG/09/012/28096/British Heart Foundation/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):713-20. doi: 10.1038/nature08979.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360734" target="_blank"〉PubMed〈/a〉

Description: Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of 〈or=5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173859/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173859/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HapMap 3 Consortium -- Altshuler, David M -- Gibbs, Richard A -- Peltonen, Leena -- Dermitzakis, Emmanouil -- Schaffner, Stephen F -- Yu, Fuli -- Bonnen, Penelope E -- de Bakker, Paul I W -- Deloukas, Panos -- Gabriel, Stacey B -- Gwilliam, Rhian -- Hunt, Sarah -- Inouye, Michael -- Jia, Xiaoming -- Palotie, Aarno -- Parkin, Melissa -- Whittaker, Pamela -- Chang, Kyle -- Hawes, Alicia -- Lewis, Lora R -- Ren, Yanru -- Wheeler, David -- Muzny, Donna Marie -- Barnes, Chris -- Darvishi, Katayoon -- Hurles, Matthew -- Korn, Joshua M -- Kristiansson, Kati -- Lee, Charles -- McCarrol, Steven A -- Nemesh, James -- Keinan, Alon -- Montgomery, Stephen B -- Pollack, Samuela -- Price, Alkes L -- Soranzo, Nicole -- Gonzaga-Jauregui, Claudia -- Anttila, Verneri -- Brodeur, Wendy -- Daly, Mark J -- Leslie, Stephen -- McVean, Gil -- Moutsianas, Loukas -- Nguyen, Huy -- Zhang, Qingrun -- Ghori, Mohammed J R -- McGinnis, Ralph -- McLaren, William -- Takeuchi, Fumihiko -- Grossman, Sharon R -- Shlyakhter, Ilya -- Hostetter, Elizabeth B -- Sabeti, Pardis C -- Adebamowo, Clement A -- Foster, Morris W -- Gordon, Deborah R -- Licinio, Julio -- Manca, Maria Cristina -- Marshall, Patricia A -- Matsuda, Ichiro -- Ngare, Duncan -- Wang, Vivian Ota -- Reddy, Deepa -- Rotimi, Charles N -- Royal, Charmaine D -- Sharp, Richard R -- Zeng, Changqing -- Brooks, Lisa D -- McEwen, Jean E -- 068545/Wellcome Trust/United Kingdom -- 068545/Z/02/Wellcome Trust/United Kingdom -- 076113/Wellcome Trust/United Kingdom -- 077011/Wellcome Trust/United Kingdom -- 077014/Wellcome Trust/United Kingdom -- 082371/Wellcome Trust/United Kingdom -- 089061/Wellcome Trust/United Kingdom -- 089062/Wellcome Trust/United Kingdom -- 091746/Wellcome Trust/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- P30 DK043351/DK/NIDDK NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Sep 2;467(7311):52-8. doi: 10.1038/nature09298.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02138, USA. altshuler@molbio.mgh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20811451" target="_blank"〉PubMed〈/a〉

Description: A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly 10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA interference genetic screen revealed that a BCR signalling component, Bruton's tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs in these ABC DLBCLs formed prominent clusters in the plasma membrane with low diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM) signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated. These mutations increased surface BCR expression and attenuated Lyn kinase, a feedback inhibitor of BCR signalling. These findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845535/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845535/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, R Eric -- Ngo, Vu N -- Lenz, Georg -- Tolar, Pavel -- Young, Ryan M -- Romesser, Paul B -- Kohlhammer, Holger -- Lamy, Laurence -- Zhao, Hong -- Yang, Yandan -- Xu, Weihong -- Shaffer, Arthur L -- Wright, George -- Xiao, Wenming -- Powell, John -- Jiang, Jian-Kang -- Thomas, Craig J -- Rosenwald, Andreas -- Ott, German -- Muller-Hermelink, Hans Konrad -- Gascoyne, Randy D -- Connors, Joseph M -- Johnson, Nathalie A -- Rimsza, Lisa M -- Campo, Elias -- Jaffe, Elaine S -- Wilson, Wyndham H -- Delabie, Jan -- Smeland, Erlend B -- Fisher, Richard I -- Braziel, Rita M -- Tubbs, Raymond R -- Cook, J R -- Weisenburger, Dennis D -- Chan, Wing C -- Pierce, Susan K -- Staudt, Louis M -- NIH0011349228/PHS HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):88-92. doi: 10.1038/nature08638.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054396" target="_blank"〉PubMed〈/a〉

Description: The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-kappaB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-kappaB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-beta. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ngo, Vu N -- Young, Ryan M -- Schmitz, Roland -- Jhavar, Sameer -- Xiao, Wenming -- Lim, Kian-Huat -- Kohlhammer, Holger -- Xu, Weihong -- Yang, Yandan -- Zhao, Hong -- Shaffer, Arthur L -- Romesser, Paul -- Wright, George -- Powell, John -- Rosenwald, Andreas -- Muller-Hermelink, Hans Konrad -- Ott, German -- Gascoyne, Randy D -- Connors, Joseph M -- Rimsza, Lisa M -- Campo, Elias -- Jaffe, Elaine S -- Delabie, Jan -- Smeland, Erlend B -- Fisher, Richard I -- Braziel, Rita M -- Tubbs, Raymond R -- Cook, J R -- Weisenburger, Denny D -- Chan, Wing C -- Staudt, Louis M -- U01-CA 114778/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Feb 3;470(7332):115-9. doi: 10.1038/nature09671. Epub 2010 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179087" target="_blank"〉PubMed〈/a〉

Description: Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) 〉or= 40 kg m(-2) or BMI standard deviation score 〉or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880448/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880448/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walters, R G -- Jacquemont, S -- Valsesia, A -- de Smith, A J -- Martinet, D -- Andersson, J -- Falchi, M -- Chen, F -- Andrieux, J -- Lobbens, S -- Delobel, B -- Stutzmann, F -- El-Sayed Moustafa, J S -- Chevre, J-C -- Lecoeur, C -- Vatin, V -- Bouquillon, S -- Buxton, J L -- Boute, O -- Holder-Espinasse, M -- Cuisset, J-M -- Lemaitre, M-P -- Ambresin, A-E -- Brioschi, A -- Gaillard, M -- Giusti, V -- Fellmann, F -- Ferrarini, A -- Hadjikhani, N -- Campion, D -- Guilmatre, A -- Goldenberg, A -- Calmels, N -- Mandel, J-L -- Le Caignec, C -- David, A -- Isidor, B -- Cordier, M-P -- Dupuis-Girod, S -- Labalme, A -- Sanlaville, D -- Beri-Dexheimer, M -- Jonveaux, P -- Leheup, B -- Ounap, K -- Bochukova, E G -- Henning, E -- Keogh, J -- Ellis, R J -- Macdermot, K D -- van Haelst, M M -- Vincent-Delorme, C -- Plessis, G -- Touraine, R -- Philippe, A -- Malan, V -- Mathieu-Dramard, M -- Chiesa, J -- Blaumeiser, B -- Kooy, R F -- Caiazzo, R -- Pigeyre, M -- Balkau, B -- Sladek, R -- Bergmann, S -- Mooser, V -- Waterworth, D -- Reymond, A -- Vollenweider, P -- Waeber, G -- Kurg, A -- Palta, P -- Esko, T -- Metspalu, A -- Nelis, M -- Elliott, P -- Hartikainen, A-L -- McCarthy, M I -- Peltonen, L -- Carlsson, L -- Jacobson, P -- Sjostrom, L -- Huang, N -- Hurles, M E -- O'Rahilly, S -- Farooqi, I S -- Mannik, K -- Jarvelin, M-R -- Pattou, F -- Meyre, D -- Walley, A J -- Coin, L J M -- Blakemore, A I F -- Froguel, P -- Beckmann, J S -- 077014/Wellcome Trust/United Kingdom -- 079534/Wellcome Trust/United Kingdom -- 082390/Wellcome Trust/United Kingdom -- 089061/Wellcome Trust/United Kingdom -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- G0500539/Medical Research Council/United Kingdom -- G0600331/Medical Research Council/United Kingdom -- G0600331(77796)/Medical Research Council/United Kingdom -- G0900554/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Feb 4;463(7281):671-5. doi: 10.1038/nature08727.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Genomic Medicine, Imperial College London, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130649" target="_blank"〉PubMed〈/a〉

Description: Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075879/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075879/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graveley, Brenton R -- Brooks, Angela N -- Carlson, Joseph W -- Duff, Michael O -- Landolin, Jane M -- Yang, Li -- Artieri, Carlo G -- van Baren, Marijke J -- Boley, Nathan -- Booth, Benjamin W -- Brown, James B -- Cherbas, Lucy -- Davis, Carrie A -- Dobin, Alex -- Li, Renhua -- Lin, Wei -- Malone, John H -- Mattiuzzo, Nicolas R -- Miller, David -- Sturgill, David -- Tuch, Brian B -- Zaleski, Chris -- Zhang, Dayu -- Blanchette, Marco -- Dudoit, Sandrine -- Eads, Brian -- Green, Richard E -- Hammonds, Ann -- Jiang, Lichun -- Kapranov, Phil -- Langton, Laura -- Perrimon, Norbert -- Sandler, Jeremy E -- Wan, Kenneth H -- Willingham, Aarron -- Zhang, Yu -- Zou, Yi -- Andrews, Justen -- Bickel, Peter J -- Brenner, Steven E -- Brent, Michael R -- Cherbas, Peter -- Gingeras, Thomas R -- Hoskins, Roger A -- Kaufman, Thomas C -- Oliver, Brian -- Celniker, Susan E -- U01 HB004271/HB/NHLBI NIH HHS/ -- U01 HG004271/HG/NHGRI NIH HHS/ -- U01 HG004271-01/HG/NHGRI NIH HHS/ -- ZIA DK015600-14/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 24;471(7339):473-9. doi: 10.1038/nature09715. Epub 2010 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030-6403, USA. graveley@neuron.uchc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179090" target="_blank"〉PubMed〈/a〉