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Editorial

Growing access to phenotype data p99

doi:10.1038/ng.3213

Plant genomes are the index that will allow plant breeders and researchers to access the information contained in the world's seed banks, with each allele linking germplasm, genotype and phenotype. The journal endorses the international DivSeek initiative and will work with authors to ensure access to phenotype data linked to published genetic data.


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News and Views

Using iPSCs and genomics to catch CNVs in the act pp100 - 101

Alexander Eckehart Urban & Carolin Purmann

doi:10.1038/ng.3204

See also: Article by Adamo et al.


New insight into a complex plant–fungal pathogen interaction pp101 - 103

Peter J Balint-Kurti & James B Holland

doi:10.1038/ng.3203

See also: Article by Zuo et al.


Big data mining yields novel insights on cancer pp103 - 104

Peng Jiang & X Shirley Liu

doi:10.1038/ng.3205

See also: Analysis by Fehrmann et al.


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Analysis

Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes pp106 - 114

Mark D M Leiserson, Fabio Vandin, Hsin-Ta Wu, Jason R Dobson, Jonathan V Eldridge, Jacob L Thomas, Alexandra Papoutsaki, Younhun Kim, Beifang Niu, Michael McLellan, Michael S Lawrence, Abel Gonzalez-Perez, David Tamborero, Yuwei Cheng, Gregory A Ryslik, Nuria Lopez-Bigas, Gad Getz, Li Ding & Benjamin J Raphael

doi:10.1038/ng.3168

Benjamin Raphael and colleagues report an analysis of altered subnetworks of somatic aberrations in TCGA pan-cancer data sets, including 3,281 samples from 12 cancer types, using a newly developed HotNet2 algorithm. They identify 16 significantly mutated subnetworks and provide a more comprehensive view into altered pathways, including those with known roles in cancer development.


Gene expression analysis identifies global gene dosage sensitivity in cancer pp115 - 125

Rudolf S N Fehrmann, Juha M Karjalainen, Małgorzata Krajewska, Harm-Jan Westra, David Maloney, Anton Simeonov, Tune H Pers, Joel N Hirschhorn, Ritsert C Jansen, Erik A Schultes, Herman H H B M van Haagen, Elisabeth G E de Vries, Gerard J te Meerman, Cisca Wijmenga, Marcel A T M van Vugt & Lude Franke

doi:10.1038/ng.3173

Rudolf Fehrmann, Lude Franke and colleagues report a method for capturing the variation present within mammalian transcriptomes in a limited number of 'transcriptional components' and demonstrate widespread correlation between gene copy number and expression levels. The method allows for the inference of candidate gene function and the identification of potential therapeutic targets in cancer.

See also: News and Views by Jiang & Liu


No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans pp126 - 131

Ron Do, Daniel Balick, Heng Li, Ivan Adzhubei, Shamil Sunyaev & David Reich

doi:10.1038/ng.3186

David Reich, Shamil Sunyaev and colleagues report an analysis of the per-genome accumulation of nonsynonymous substitutions across diverse pairs of human populations. They find no evidence for a higher load of deleterious mutations in non-Africans than in West Africans and show that the observed patterns are not likely to reflect changes in natural selection.


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Articles

7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages pp132 - 141

Antonio Adamo, Sina Atashpaz, Pierre-Luc Germain, Matteo Zanella, Giuseppe D'Agostino, Veronica Albertin, Josh Chenoweth, Lucia Micale, Carmela Fusco, Christian Unger, Bartolomeo Augello, Orazio Palumbo, Brad Hamilton, Massimo Carella, Emilio Donti, Giancarlo Pruneri, Angelo Selicorni, Elisa Biamino, Paolo Prontera, Ronald McKay, Giuseppe Merla & Giuseppe Testa

doi:10.1038/ng.3169

Giuseppe Testa and colleagues report the generation and transcriptional characterization of patient-derived induced pluripotent stem cells (iPSCs) with copy number variants at 7q11.23, which cause syndromes including neurocognitive phenotypes. They find that the dosage of the transcription factor gene GTF2I accounts for 10–20% of the transcriptional dysregulation observed in these cells.

See also: News and Views by Urban & Purmann


Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression pp142 - 150

Haruna Takeda, Zhubo Wei, Hideto Koso, Alistair G Rust, Christopher Chin Kuan Yew, Michael B Mann, Jerrold M Ward, David J Adams, Neal G Copeland & Nancy A Jenkins

doi:10.1038/ng.3175

Nancy Jenkins and colleagues report the use of Sleeping Beauty transposon mutagenesis screens in mice to identify new genes involved in tumor progression in colorectal cancer. They identify 111 common transposon insertion sites present in all cohorts, including Znf292, a new tumor suppressor whose human counterpart is also mutated in human colorectal cancer.


A maize wall-associated kinase confers quantitative resistance to head smut pp151 - 157

Weiliang Zuo, Qing Chao, Nan Zhang, Jianrong Ye, Guoqing Tan, Bailin Li, Yuexian Xing, Boqi Zhang, Haijun Liu, Kevin A Fengler, Jing Zhao, Xianrong Zhao, Yongsheng Chen, Jinsheng Lai, Jianbing Yan & Mingliang Xu

doi:10.1038/ng.3170

Mingliang Xu and colleagues show that a wall-associated kinase, ZmWAK, confers resistance to maize head smut, a systemic fungal disease in maize.

See also: News and Views by Balint-Kurti & Holland


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Letters

Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism pp158 - 163

Zheng Hu, Da Zhu, Wei Wang, Weiyang Li, Wenlong Jia, Xi Zeng, Wencheng Ding, Lan Yu, Xiaoli Wang, Liming Wang, Hui Shen, Changlin Zhang, Hongjie Liu, Xiao Liu, Yi Zhao, Xiaodong Fang, Shuaicheng Li, Wei Chen, Tang Tang, Aisi Fu, Zou Wang, Gang Chen, Qinglei Gao, Shuang Li, Ling Xi, Changyu Wang, Shujie Liao, Xiangyi Ma, Peng Wu, Kezhen Li, Shixuan Wang, Jianfeng Zhou, Jun Wang, Xun Xu, Hui Wang & Ding Ma

doi:10.1038/ng.3178

Ding Ma, Hui Wang, Xun Xu and colleagues report a genome-wide map of HPV integration sites in cervical cancer samples and cell lines. In addition to discovering new integration hot spots, the authors identify microhomology-mediated DNA repair as a likely mechanism by which HPV integrates into the human genome.


Identification of six new susceptibility loci for invasive epithelial ovarian cancer pp164 - 171

Karoline B Kuchenbaecker, Susan J Ramus, Jonathan Tyrer, Andrew Lee, Howard C Shen, Jonathan Beesley, Kate Lawrenson, Lesley McGuffog, Sue Healey, Janet M Lee, Tassja J Spindler, Yvonne G Lin, Tanja Pejovic, Yukie Bean, Qiyuan Li, Simon Coetzee, Dennis Hazelett, Alexander Miron, Melissa Southey, Mary Beth Terry, David E Goldgar, Saundra S Buys, Ramunas Janavicius, Cecilia M Dorfling, Elizabeth J van Rensburg, Susan L Neuhausen, Yuan Chun Ding, Thomas V O Hansen, Lars Jønson, Anne-Marie Gerdes, Bent Ejlertsen, Daniel Barrowdale, Joe Dennis, Javier Benitez, Ana Osorio, Maria Jose Garcia, Ian Komenaka, Jeffrey N Weitzel, Pamela Ganschow, Paolo Peterlongo, Loris Bernard, Alessandra Viel, Bernardo Bonanni, Bernard Peissel, Siranoush Manoukian, Paolo Radice, Laura Papi, Laura Ottini, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Debra Frost, Jo Perkins, Radka Platte, Steve Ellis, EMBRACE, Andrew K Godwin, Rita Katharina Schmutzler, Alfons Meindl, Christoph Engel, Christian Sutter, Olga M Sinilnikova, GEMO Study Collaborators, Francesca Damiola, Sylvie Mazoyer, Dominique Stoppa-Lyonnet, Kathleen Claes, Kim De Leeneer, Judy Kirk, Gustavo C Rodriguez, Marion Piedmonte, David M O'Malley, Miguel de la Hoya, Trinidad Caldes, Kristiina Aittomäki, Heli Nevanlinna, J Margriet Collée, Matti A Rookus, Jan C Oosterwijk, Breast Cancer Family Registry, Laima Tihomirova, Nadine Tung, Ute Hamann, Claudine Isaccs, Marc Tischkowitz, Evgeny N Imyanitov, Maria A Caligo, Ian G Campbell, Frans B L Hogervorst, HEBON, Edith Olah, Orland Diez, Ignacio Blanco, Joan Brunet, Conxi Lazaro, Miquel Angel Pujana, Anna Jakubowska, Jacek Gronwald, Jan Lubinski, Grzegorz Sukiennicki, Rosa B Barkardottir, Marie Plante, Jacques Simard, Penny Soucy, Marco Montagna, Silvia Tognazzo, Manuel R Teixeira, KConFab Investigators, Vernon S Pankratz, Xianshu Wang, Noralane Lindor, Csilla I Szabo, Noah Kauff, Joseph Vijai, Carol A Aghajanian, Georg Pfeiler, Andreas Berger, Christian F Singer, Muy-Kheng Tea, Catherine M Phelan, Mark H Greene, Phuong L Mai, Gad Rennert, Anna Marie Mulligan, Sandrine Tchatchou, Irene L Andrulis, Gord Glendon, Amanda Ewart Toland, Uffe Birk Jensen, Torben A Kruse, Mads Thomassen, Anders Bojesen, Jamal Zidan, Eitan Friedman, Yael Laitman, Maria Soller, Annelie Liljegren, Brita Arver, Zakaria Einbeigi, Marie Stenmark-Askmalm, Olufunmilayo I Olopade, Robert L Nussbaum, Timothy R Rebbeck, Katherine L Nathanson, Susan M Domchek, Karen H Lu, Beth Y Karlan, Christine Walsh, Jenny Lester, Australian Cancer Study (Ovarian Cancer Investigators), Australian Ovarian Cancer Study Group, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Peter A Fasching, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Sandrina Lambrechts, Ed Dicks, Jennifer A Doherty, Kristine G Wicklund, Mary Anne Rossing, Anja Rudolph, Jenny Chang-Claude, Shan Wang-Gohrke, Ursula Eilber, Kirsten B Moysich, Kunle Odunsi, Lara Sucheston, Shashi Lele, Lynne R Wilkens, Marc T Goodman, Pamela J Thompson, Yurii B Shvetsov, Ingo B Runnebaum, Matthias Dürst, Peter Hillemanns, Thilo Dörk, Natalia Antonenkova, Natalia Bogdanova, Arto Leminen, Liisa M Pelttari, Ralf Butzow, Francesmary Modugno, Joseph L Kelley, Robert P Edwards, Roberta B Ness, Andreas du Bois, Florian Heitz, Ira Schwaab, Philipp Harter, Keitaro Matsuo, Satoyo Hosono, Sandra Orsulic, Allan Jensen, Susanne Kruger Kjaer, Estrid Hogdall, Hanis Nazihah Hasmad, Mat Adenan Noor Azmi, Soo-Hwang Teo, Yin-Ling Woo, Brooke L Fridley, Ellen L Goode, Julie M Cunningham, Robert A Vierkant, Fiona Bruinsma, Graham G Giles, Dong Liang, Michelle A T Hildebrandt, Xifeng Wu, Douglas A Levine, Maria Bisogna, Andrew Berchuck, Edwin S Iversen, Joellen M Schildkraut, Patrick Concannon, Rachel Palmieri Weber, Daniel W Cramer, Kathryn L Terry, Elizabeth M Poole, Shelley S Tworoger, Elisa V Bandera, Irene Orlow, Sara H Olson, Camilla Krakstad, Helga B Salvesen, Ingvild L Tangen, Line Bjorge, Anne M van Altena, Katja K H Aben, Lambertus A Kiemeney, Leon F A G Massuger, Melissa Kellar, Angela Brooks-Wilson, Linda E Kelemen, Linda S Cook, Nhu D Le, Cezary Cybulski, Hannah Yang, Jolanta Lissowska, Louise A Brinton, Nicolas Wentzensen, Claus Hogdall, Lene Lundvall, Lotte Nedergaard, Helen Baker, Honglin Song, Diana Eccles, Ian McNeish, James Paul, Karen Carty, Nadeem Siddiqui, Rosalind Glasspool, Alice S Whittemore, Joseph H Rothstein, Valerie McGuire, Weiva Sieh, Bu-Tian Ji, Wei Zheng, Xiao-Ou Shu, Yu-Tang Gao, Barry Rosen, Harvey A Risch, John R McLaughlin, Steven A Narod, Alvaro N Monteiro, Ann Chen, Hui-Yi Lin, Jenny Permuth-Wey, Thomas A Sellers, Ya-Yu Tsai, Zhihua Chen, Argyrios Ziogas, Hoda Anton-Culver, Aleksandra Gentry-Maharaj, Usha Menon, Patricia Harrington, Alice W Lee, Anna H Wu, Celeste L Pearce, Gerry Coetzee, Malcolm C Pike, Agnieszka Dansonka-Mieszkowska, Agnieszka Timorek, Iwona K Rzepecka, Jolanta Kupryjanczyk, Matt Freedman, Houtan Noushmehr, Douglas F Easton, Kenneth Offit, Fergus J Couch, Simon Gayther, Paul P Pharoah, Antonis C Antoniou, Georgia Chenevix-Trench & the Consortium of Investigators of Modifiers of BRCA1 and BRCA2

doi:10.1038/ng.3185

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.


High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis pp172 - 179

Philippe Goyette, Gabrielle Boucher, Dermot Mallon, Eva Ellinghaus, Luke Jostins, Hailiang Huang, Stephan Ripke, Elena S Gusareva, Vito Annese, Stephen L Hauser, Jorge R Oksenberg, Ingo Thomsen, Stephen Leslie, International Inflammatory Bowel Disease Genetics Consortium, Mark J Daly, Kristel Van Steen, Richard H Duerr, Jeffrey C Barrett, Dermot P B McGovern, L Philip Schumm, James A Traherne, Mary N Carrington, Vasilis Kosmoliaptsis, Tom H Karlsen, Andre Franke & John D Rioux

doi:10.1038/ng.3176

John Rioux, Andre Franke, Tom Karlsen and colleagues perform a fine-mapping study of the HLA region in Crohn's disease and ulcerative colitis. They identify a primary role for HLA-DRB1*01:03 in both diseases and find evidence of heterozygous advantage in protection against ulcerative colitis.


Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy pp180 - 185

Michael Y Zhang, Jane E Churpek, Siobán B Keel, Tom Walsh, Ming K Lee, Keith R Loeb, Suleyman Gulsuner, Colin C Pritchard, Marilyn Sanchez-Bonilla, Jeffrey J Delrow, Ryan S Basom, Melissa Forouhar, Boglarka Gyurkocza, Bradford S Schwartz, Barbara Neistadt, Rafael Marquez, Christopher J Mariani, Scott A Coats, Inga Hofmann, R Coleman Lindsley, David A Williams, Janis L Abkowitz, Marshall S Horwitz, Mary-Claire King, Lucy A Godley & Akiko Shimamura

doi:10.1038/ng.3177

Akiko Shimamura and colleagues report the identification of dominant-negative germline variants in ETV6 that cause thrombocytopenia and hematologic malignancies in the affected members of three families. All three mutations alter conserved amino acids in the transcriptional repressor encoded by ETV6 and affect its DNA binding.


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Corrigendum

Corrigendum: The genome sequence of the orchid Phalaenopsis equestris p186

Jing Cai, Xin Liu, Kevin Vanneste, Sebastian Proost, Wen-Chieh Tsai, Ke-Wei Liu, Li-Jun Chen, Ying He, Qing Xu, Chao Bian, Zhijun Zheng, Fengming Sun, Weiqing Liu, Yu-Yun Hsiao, Zhao-Jun Pan, Chia-Chi Hsu, Ya-Ping Yang, Yi-Chin Hsu, Yu-Chen Chuang, Anne Dievart, Jean-Francois Dufayard, Xun Xu, Jun-Yi Wang, Jun Wang, Xin-Ju Xiao, Xue-Min Zhao, Rong Du, Guo-Qiang Zhang, Meina Wang, Yong-Yu Su, Gao-Chang Xie, Guo-Hui Liu, Li-Qiang Li, Lai-Qiang Huang, Yi-Bo Luo, Hong-Hwa Chen, Yves Van de Peer & Zhong-Jian Liu

doi:10.1038/ng0215-186


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