Nature Genetics Contents: December 2014 pp 1251 - 1372

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Advertisement A*STAR Research - Highlighting the best of research at the Agency for Science, Technology and Research (A*STAR), Singapore's premier research organization Recent Highlights  Bioinformatics: A better way to design genes | Cancer: Lighting up tumors | Immunology: Immune cells' repertoire revealed Download the A*STAR Research app now! TABLE OF CONTENTS December 2014 Volume 46, Issue 12 Editorial News and Views Research Highlights Analysis Brief Communication Articles Letters Technical Reports Corrigendum Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Outlook Rice Scientists are starting a rice revolution to feed a hungry world. By decoding genetics, improving breeding and, perhaps, reshaping the plant?s biology, researchers are working to take the world?s most vital crop into the future.  Access the Outlook free online for six months.   Editorial Top Second call for pan-cancer analysis   p1251 doi:10.1038/ng.3155 We invite proposals by 1 March for pan-cancer analyses from public data sets to be submitted by the end of 2015. We will coordinate expressions of interest from the Nature family of journals and index the resulting publications prominently in a web focus and special issue of the journal. News and Views Top Predicting protein networks in cancer   pp1252 - 1253 Andrea Califano doi:10.1038/ng.3156 Characterization of the mutational landscape of tumors is important to understanding disease etiology but does not provide mechanistic insight into the functional role of specific mutations. A new study introduces a statistical mechanical framework that draws on biophysical data from SH2 domain-phosphoprotein interactions to predict the functional effects of mutations in cancer. See also: Technical Report by AlQuraishi et al. A shared architecture for promoters and enhancers   pp1253 - 1254 Shira Weingarten-Gabbay & Eran Segal doi:10.1038/ng.3152 A new study detects unstable nascent RNAs and uncovers thousands of transcription initiation sites in promoters and enhancers. Detailed analysis shows that these initiation sites have a similar architecture and that they are differentiated by post-transcriptional regulation rather than transcription initiation. See also: Article by Core et al. Feverish prospects for seizure genetics   pp1255 - 1256 Sanjay Sisodiya doi:10.1038/ng.3150 Febrile seizures can arise in response to fevers induced by viral infection or as an adverse reaction to live-virus vaccines such as measles, mumps and rubella (MMR) vaccination. A new study has now identified common genetic variants influencing susceptibility to febrile seizures, including two loci specifically associated with MMR-related events. See also: Article by Feenstra et al. Genetics JOBS of the week Postdoctoral Associate- Genetics & Circuitry of Sleep Johns Hopkins University Faculty Position in the Discipline of Genetics Memorial University Faculty Position Department of Genetics and Genome Sciences Case Western Reserve University, School of Medicine Scientist Position in Human Molecular Genetics University of Toronto NIH / NCI Postdoctoral Position in RNA Biology and Gene Therapy NIH/NCI-National Institutes of Health More Science jobs from Genetics EVENT Malaria Experimental Genetics 15.03.15 Bangkok, Thailand More science events from Research Highlights Top Single-haplotype genome assembly | Modeling Ebola hemorrhagic fever in mice | Cohesin and chromosome loops | Fine mapping with function | Persimmon sex determination Analysis Top Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types   pp1258 - 1263 Nils J Fredriksson, Lars Ny, Jonas A Nilsson & Erik Larsson doi:10.1038/ng.3141 Erik Larsson and colleagues present an analysis pipeline for identifying likely transcription-altering noncoding somatic mutations in cancer using publicly available data from 505 tumor genomes across 14 cancer types. They find that TERT promoter mutations show strong associations to altered transcriptional levels and identify recurrent promoter mutations in DPH3 and PLEKHS1. Brief Communication Top RNF43 is frequently mutated in colorectal and endometrial cancers   pp1264 - 1266 Marios Giannakis, Eran Hodis, Xinmeng Jasmine Mu, Mai Yamauchi, Joseph Rosenbluh, Kristian Cibulskis, Gordon Saksena, Michael S Lawrence, Zhi Rong Qian, Reiko Nishihara, Eliezer M Van Allen, William C Hahn, Stacey B Gabriel, Eric S Lander, Gad Getz, Shuji Ogino, Charles S Fuchs & Levi A Garraway doi:10.1038/ng.3127 Levi Garraway and colleagues report the identification of somatic mutations of RNF43, which encodes an E3 ubiquitin ligase that negatively regulates Wnt signaling, in over 18% of colorectal adenocarcinomas and endometrial carcinomas. Articles Top Trans-ancestry mutational landscape of hepatocellular carcinoma genomes   pp1267 - 1273 Yasushi Totoki, Kenji Tatsuno, Kyle R Covington, Hiroki Ueda, Chad J Creighton, Mamoru Kato, Shingo Tsuji, Lawrence A Donehower, Betty L Slagle, Hiromi Nakamura, Shogo Yamamoto, Eve Shinbrot, Natsuko Hama, Megan Lehmkuhl, Fumie Hosoda, Yasuhito Arai, Kim Walker, Mahmoud Dahdouli, Kengo Gotoh, Genta Nagae, Marie-Claude Gingras, Donna M Muzny, Hidenori Ojima, Kazuaki Shimada, Yutaka Midorikawa, John A Goss, Ronald Cotton, Akimasa Hayashi, Junji Shibahara, Shumpei Ishikawa, Jacfranz Guiteau, Mariko Tanaka, Tomoko Urushidate, Shoko Ohashi, Naoko Okada, Harsha Doddapaneni, Min Wang, Yiming Zhu, Huyen Dinh, Takuji Okusaka, Norihiro Kokudo, Tomoo Kosuge, Tadatoshi Takayama, Masashi Fukayama, Richard A Gibbs, David A Wheeler, Hiroyuki Aburatani & Tatsuhiro Shibata doi:10.1038/ng.3126 Tatsuhiro Shibata, David Wheeler, Hiroyuki Aburatani and colleagues report the genomic, exomic and oncoviral sequencing of hundreds of liver cancers from the United States and Japan. The authors analyzed mutation patterns and identified signatures unique to the Asian cases. Common variants associated with general and MMR vaccine-related febrile seizures   pp1274 - 1282 Bjarke Feenstra, Björn Pasternak, Frank Geller, Lisbeth Carstensen, Tongfei Wang, Fen Huang, Jennifer L Eitson, Mads V Hollegaard, Henrik Svanström, Mogens Vestergaard, David M Hougaard, John W Schoggins, Lily Yeh Jan, Mads Melbye & Anders Hviid doi:10.1038/ng.3129 Bjarke Feenstra and colleagues identify common variants at six loci associated with general or MMR vaccine-related febrile seizures. The two loci specifically associated with MMR-related febrile seizures harbor the interferon-stimulated gene IFI44L and the measles virus receptor gene CD46. See also: News and Views by Sisodiya Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy   pp1283 - 1292 Carol-Anne Martin, Ilyas Ahmad, Anna Klingseisen, Muhammad Sajid Hussain, Louise S Bicknell, Andrea Leitch, Gudrun Nürnberg, Mohammad Reza Toliat, Jennie E Murray, David Hunt, Fawad Khan, Zafar Ali, Sigrid Tinschert, James Ding, Charlotte Keith, Margaret E Harley, Patricia Heyn, Rolf Müller, Ingrid Hoffmann, Valérie Cormier Daire, Hélène Dollfus, Lucie Dupuis, Anu Bashamboo, Kenneth McElreavey, Ariana Kariminejad, Roberto Mendoza-Londono, Anthony T Moore, Anand Saggar, Catie Schlechter, Richard Weleber, Holger Thiele, Janine Altmüller, Wolfgang Höhne, Matthew E Hurles, Angelika Anna Noegel, Shahid Mahmood Baig, Peter Nürnberg & Andrew P Jackson doi:10.1038/ng.3122 Andrew Jackson, Peter Nurnberg and colleagues identify mutations in PLK4 and TUBGCP6 in individuals with microcephaly, primordial dwarfism, retinopathy and other congenital anomalies. These findings extend the spectrum of human phenotypes associated with centriole dysfunction. Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability   pp1293 - 1302 Francesca Antonacci, Megan Y Dennis, John Huddleston, Peter H Sudmant, Karyn Meltz Steinberg, Jill A Rosenfeld, Mattia Miroballo, Tina A Graves, Laura Vives, Maika Malig, Laura Denman, Archana Raja, Andrew Stuart, Joyce Tang, Brenton Munson, Lisa G Shaffer, Chris T Amemiya, Richard K Wilson & Evan E Eichler doi:10.1038/ng.3120 Evan Eichler and colleagues present a detailed characterization of the chromosome 15q13.3 microdeletion region. They identify complex structural polymorphisms and find that the rearrangement breakpoints cluster in palindromic GOLGA8 core duplicons, providing evidence that this repeat and its palindromic architecture underlie the evolutionary and disease-related instability of this region. Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history OPEN   pp1303 - 1310 Xuming Zhou, Boshi Wang, Qi Pan, Jinbo Zhang, Sudhir Kumar, Xiaoqing Sun, Zhijin Liu, Huijuan Pan, Yu Lin, Guangjian Liu, Wei Zhan, Mingzhou Li, Baoping Ren, Xingyong Ma, Hang Ruan, Chen Cheng, Dawei Wang, Fanglei Shi, Yuanyuan Hui, Yujing Tao, Chenglin Zhang, Pingfen Zhu, Zuofu Xiang, Wenkai Jiang, Jiang Chang, Hailong Wang, Zhisheng Cao, Zhi Jiang, Baoguo Li, Guang Yang, Christian Roos, Paul A Garber, Michael W Bruford, Ruiqiang Li & Ming Li doi:10.1038/ng.3137 Ming Li, Ruiqiang Li and colleagues report the whole-genome sequencing of a male golden snub-nosed monkey, Rhinopithecus roxellana, as well as its relatives Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri. Their analysis provides insights into primate evolution and adaptation to a diet consisting primarily of leaves and seeds. Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers   pp1311 - 1320 Leighton J Core, André L Martins, Charles G Danko, Colin T Waters, Adam Siepel & John T Lis doi:10.1038/ng.3142 John Lis, Adam Siepel and colleagues map transcription start sites across the genome in two human cell lines using a nuclear run-on protocol called GRO-cap. They find a common architecture of initiation at both promoters and enhancers and that transcript elongation stability provides the strongest distinction between promoters and enhancers. See also: News and Views by Weingarten-Gabbay & Segal Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution   pp1321 - 1326 Astrid von Mentzer, Thomas R Connor, Lothar H Wieler, Torsten Semmler, Atsushi Iguchi, Nicholas R Thomson, David A Rasko, Enrique Joffre, Jukka Corander, Derek Pickard, Gudrun Wiklund, Ann-Mari Svennerholm, Åsa Sjöling & Gordon Dougan doi:10.1038/ng.3145 Astrid von Mentzer, Gordon Dougan and colleagues report the whole-genome sequencing of a representative global collection of enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea, including samples from 20 countries isolated between 1980 and 2011. They find that, although ETEC isolates are widely distributed across the E. coli species and are genetically diverse, there are several discrete lineages that have contributed to overlapping global epidemics. Letters Top Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes   pp1327 - 1332 Julian Schubert, Aleksandra Siekierska, Mélanie Langlois, Patrick May, Clément Huneau, Felicitas Becker, Hiltrud Muhle, Arvid Suls, Johannes R Lemke, Carolien G F de Kovel, Holger Thiele, Kathryn Konrad, Amit Kawalia, Mohammad R Toliat, Thomas Sander, Franz Rüschendorf, Almuth Caliebe, Inga Nagel, Bernard Kohl, Angela Kecskés, Maxime Jacmin, Katia Hardies, Sarah Weckhuysen, Erik Riesch, Thomas Dorn, Eva H Brilstra, Stephanie Baulac, Rikke S Møller, Helle Hjalgrim, Bobby P C Koeleman, EuroEPINOMICS RES Consortium, Karin Jurkat-Rott, Frank Lehman-Horn, Jared C Roach, Gustavo Glusman, Leroy Hood, David J Galas, Benoit Martin, Peter A M de Witte, Saskia Biskup, Peter De Jonghe, Ingo Helbig, Rudi Balling, Peter Nürnberg, Alexander D Crawford, Camila V Esguerra, Yvonne G Weber & Holger Lerche doi:10.1038/ng.3130 Holger Lerche, Camila Esguerra and colleagues report the identification of inactivating mutations in STX1B in individuals with various seizure-related disorders, including febrile seizures and epilepsy. Functional studies indicate that STX1B acts in the presynaptic release machinery. Variation at HLA-DRB1 is associated with resistance to enteric fever   pp1333 - 1336 Sarah J Dunstan, Nguyen Thi Hue, Buhm Han, Zheng Li, Trinh Thi Bich Tram, Kar Seng Sim, Christopher M Parry, Nguyen Tran Chinh, Ha Vinh, Nguyen Phu Huong Lan, Nga Tran Vu Thieu, Phat Voong Vinh, Samir Koirala, Sabina Dongol, Amit Arjyal, Abhilasha Karkey, Olita Shilpakar, Christiane Dolecek, Jia Nee Foo, Le Thi Phuong, Mai Ngoc Lanh, Tan Do, Tin Aung, Do Nu Hon, Yik Ying Teo, Martin L Hibberd, Katherine L Anders, Yukinori Okada, Soumya Raychaudhuri, Cameron P Simmons, Stephen Baker, Paul I W de Bakker, Buddha Basnyat, Tran Tinh Hien, Jeremy J Farrar & Chiea Chuen Khor doi:10.1038/ng.3143 Sarah Dunstan, Chiea Chuen Khor and colleagues identify common variants in the HLA-DRB1 region associated with resistance to enteric fever. Individuals carrying the protective variants exhibit roughly five-fold higher resistance against developing this life-threatening infectious disease. Optimization of crop productivity in tomato using induced mutations in the florigen pathway   pp1337 - 1342 Soon Ju Park, Ke Jiang, Lior Tal, Yoav Yichie, Oron Gar, Dani Zamir, Yuval Eshed & Zachary B Lippman doi:10.1038/ng.3131 Zachary Lippman and colleagues report the recovery in tomato of novel, chemically induced alleles in the SFT (florigen) gene and a newly identified suppressor of the SELF PRUNING gene. These alleles, in combination with previous florigen pathway mutations, allow for the quantitative fine-tuning of fruit yield, which may be applicable to other crop species. Technical Reports Top Haplotype-resolved whole-genome sequencing by contiguity-preserving transposition and combinatorial indexing   pp1343 - 1349 Sasan Amini, Dmitry Pushkarev, Lena Christiansen, Emrah Kostem, Tom Royce, Casey Turk, Natasha Pignatelli, Andrew Adey, Jacob O Kitzman, Kandaswamy Vijayan, Mostafa Ronaghi, Jay Shendure, Kevin L Gunderson & Frank J Steemers doi:10.1038/ng.3119 Frank Steemers and colleagues report a new method for genome-wide haplotyping based on contiguity-preserving transposition and combinatorial indexing. They apply this method to assemble over 95% of the heterozygous variants in a human genome into long, accurate haplotype blocks. Comprehensive variation discovery in single human genomes   pp1350 - 1355 Neil I Weisenfeld, Shuangye Yin, Ted Sharpe, Bayo Lau, Ryan Hegarty, Laurie Holmes, Brian Sogoloff, Diana Tabbaa, Louise Williams, Carsten Russ, Chad Nusbaum, Eric S Lander, Iain MacCallum & David B Jaffe doi:10.1038/ng.3121 David Jaffe and colleagues report a new algorithm, DISCOVAR, for variant calling and de novo genome assembly. They test the algorithm on a new reference variant call set and demonstrate improved variant calling, particularly in challenging regions of the genome. Leveraging population admixture to characterize the heritability of complex traits   pp1356 - 1362 Noah Zaitlen, Bogdan Pasaniuc, Sriram Sankararaman, Gaurav Bhatia, Jianqi Zhang, Alexander Gusev, Taylor Young, Arti Tandon, Samuela Pollack, Bjarni J Vilhjálmsson, Themistocles L Assimes, Sonja I Berndt, William J Blot, Stephen Chanock, Nora Franceschini, Phyllis G Goodman, Jing He, Anselm J M Hennis, Ann Hsing, Sue A Ingles, William Isaacs, Rick A Kittles, Eric A Klein, Leslie A Lange, Barbara Nemesure, Nick Patterson, David Reich, Benjamin A Rybicki, Janet L Stanford, Victoria L Stevens, Sara S Strom, Eric A Whitsel, John S Witte, Jianfeng Xu, Christopher Haiman, James G Wilson, Charles Kooperberg, Daniel Stram, Alex P Reiner, Hua Tang & Alkes L Price doi:10.1038/ng.3139 Noah Zaitlen, Alkes Price and colleagues report a new approach to estimate the narrow-sense heritability of complex traits from unrelated individuals in a recently admixed population. They apply this approach to estimate the heritability for 13 quantitative or case-control phenotypes in 21,497 African-American individuals and suggest the inflation of family-based h2 estimates. A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks   pp1363 - 1371 Mohammed AlQuraishi, Grigoriy Koytiger, Anne Jenney, Gavin MacBeath & Peter K Sorger doi:10.1038/ng.3138 Peter Sorger, Mohammed AlQuraishi and colleagues present a statistical framework for integrating biophysical and genomic data to predict the consequences of cancer-related mutations on protein-protein interactions. They apply their framework to the SH2 phosphoprotein network using publicly available data from The Cancer Genome Atlas. See also: News and Views by Califano Corrigendum Top Corrigendum: Human somatic cell mutagenesis creates genetically tractable sarcomas   p1372 Sam D Molyneux, Paul D Waterhouse, Dawne Shelton, Yang W Shao, Christopher M Watling, Qing-Lian Tang, Isaac S Harris, Brendan C Dickson, Pirashaanthy Tharmapalan, Geir K Sandve, Xiaoyang Zhang, Swneke D Bailey, Hal Berman, Jay S Wunder, Zsuzsanna Iszvak, Mathieu Lupien, Tak W Mak & Rama Khokha doi:10.1038/ng1214-1372 Top Advertisement Nature Collections  Clinical applications of next-generation sequencing This special Collection highlights the breadth of applications of next-generation sequencing technologies in the clinic and the importance of the insights that are being gained through these methods to improve health. Produced with support from Life Technologies, a brand of Thermo Fisher Scientific.      Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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