Nature Genetics Contents: February 2015 pp 99 - 186

If you are unable to see the message below, click here to view.

TABLE OF CONTENTS February 2015 Volume 47, Issue 2 Editorial News and Views Research Highlights Analysis Articles Letters Corrigendum Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement PCR-Free Library Prep Maintains Sample Complexity for Next Gen Sequencing  Samples starting as low as 10 ng can be processed PCR-free using the Accel-NGS 2S DNA Library Kit from Swift Biosciences. The kit is able to increase library complexity, improve sample coverage, and reveal difficult to read sequences in your NGS samples. Download our application note to learn more.   Editorial Top 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. News and Views Top Using iPSCs and genomics to catch CNVs in the act   pp100 - 101 Alexander Eckehart Urban & Carolin Purmann doi:10.1038/ng.3204 Large copy number variants (CNVs) are strongly associated with morphogenetic processes and common neurodevelopmental disorders. A new study uses the example of Williams-Beuren syndrome (WBS) and Williams-Beuren region duplication syndrome to illustrate how induced pluripotent stem cells (iPSCs) and next-generation genomics can lead to a better understanding of complex genetics. 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 The coevolution of plants and microbes has shaped plant mechanisms that detect and repel pathogens. A newly identified plant gene confers partial resistance to a fungal pathogen not by preventing initial infection but by limiting its spread through the plant. 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 Recent years have seen the rapid growth of large-scale biological data, but the effective mining and modeling of 'big data' for new biological discoveries remains a significant challenge. A new study reanalyzes expression profiles from the Gene Expression Omnibus to make novel discoveries about genes involved in DNA damage repair and genome instability in cancer. See also: Analysis by Fehrmann et al. Genetics JOBS of the week Postdoctoral Fellows (Statistical and Population Genetics) Genome Institute of Singapore Statistical Data Analyst - Genetics - 29705 Washington University School of Medicine Post-Doc in Computational Biology / Genomics / Quantitative Genetics / Single Cell Analysis Ecole Polytechnique Fédérale de Lausanne (EPFL) 2-year Postdoc position in genetics of metabolism in newborns Statens Serum Institut Postdoctoral Position in Tsetse Symbiosis and Population Genetics Yale University More Science jobs from Genetics EVENT European Human Genetics Conference 2015 06.06.15 Glasgow, UK More science events from Research Highlights Top RNA splicing in common disease | Microexons on the brain | Zebrafish mutants versus morphants | AID mistargeting to enhancers | Genetic modules for autism Analysis Top 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. Articles Top 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 Letters Top 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. Corrigendum Top 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 Top Advertisement Nature Plants - Now launched  The first issue of Nature Plants has now published. Covering all aspects of plant science including genetics, cell and molecular biology, ecology, evolution, agriculture, biotechnology and economics. Explore the first issue - free access for a limited time.   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.