Nature Genetics Contents: February 2016 pp 103- 221

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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 Cancer: Genomic re-arrangement linked to gastric cancer | Obesity: Adding weight to the birth story | Genetics: Regulatory regions revealed in one shot  Download the A*STAR Research app now! TABLE OF CONTENTS February 2016 Volume 48, Issue 2 Editorial Correspondence Commentary News and Views Analysis Articles Letters Technical Reports Retraction Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Introducing HGV Database  The HGV Database is a fully searchable online database of genome variations published in peer-reviewed Data Reports in Human Genome Variation. Search and filter by specific disease, gene, region, population. Try it now    Advertisement A new open access journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. Part of the Nature Partner Journals series, the journal is published in partnership with the Center of Excellence in Genomic Medicine Research.  Open for submissions   Editorial Top Where genome editing is needed   p103 doi:10.1038/ng.3505 The journal endorses the principle of transparency in the production of genome-edited crops and livestock as a precondition for the registration of a breed or cultivar, with no further need for regulation or distinction of these goods from the products of traditional breeding. Correspondence Top Co-occurrence of MYC amplification and TP53 mutations in human cancer   pp104 - 106 Peter Ulz, Ellen Heitzer & Michael R Speicher doi:10.1038/ng.3468 Reply: Co-occurrence of MYC amplification and TP53 mutations in human cancer   pp106 - 108 Mark D M Leiserson, Fabio Vandin, Hsin-Ta Wu & Benjamin J Raphael doi:10.1038/ng.3491 Commentary Top A proposed regulatory framework for genome-edited crops   pp109 - 111 Sanwen Huang, Detlef Weigel, Roger N Beachy & Jiayang Li doi:10.1038/ng.3484 Sanwen Huang, Detlef Weigel, Roger Beachy and Jiayang Li propose a regulatory framework for precision breeding with genome-edited crops. They argue that society should benefit from the latest advances in plant genetics and genomics. News and Views Top Flavonols drive plant microevolution   pp112 - 113 Erich Grotewold doi:10.1038/ng.3490 The idea that pollinators are in large part responsible for the diversity of flowering plants dates back more than 150 years to Darwin's work, but even modern scientists have struggled to identify specific 'speciation genes' and determine how they influenced flower-pollinator interactions. A new study proposes that a series of mutations in a single gene controlling floral chemicals influenced pollinator preferences, likely resulting in speciation, bringing us closer to finding a speciation gene. See also: Article by Sheehan et al. Hybridization speeds up the emergence and evolution of a new pathogen species   pp113 - 115 Eva H Stukenbrock doi:10.1038/ng.3494 Plant pathogens can evolve new host specificities and overcome host resistances over surprisingly few generations, a process that is greatly accelerated by agricultural practices. A new study provides a striking example in which the rapid emergence of a new pathogen via introgressive hybridization mirrors the evolution of a hybrid cereal crop. See also: Letter by Menardo et al. Legionella effectors reflect strength in diversity   pp115 - 116 Inaki Comas doi:10.1038/ng.3492 The Legionella genus includes opportunistic human pathogenic species that invade human cells using effector proteins that evolved during association with their natural amoeba hosts. A new study compares the genomes of 41 Legionella species to identify nearly 6,000 effectors, providing insight into these species' evolution and pathogenic lifestyles. See also: Article by Burstein et al. Genetics JOBS of the week Professor (W3) in Genetics University of Cologne Assistant Professor Faculty Positions in Cancer Genetics Beth Israel Deaconess Medical Center - Harvard Medical School Chair, Department of Molecular Genetics, University of Toronto University of Toronto Post-doctoral position – Epigenetics of Genome Maintenance National Cancer Institute Postdoctoral Research Scientist Cancer Research UK Beatson Institute in Glasgow More Science jobs from Genetics EVENT Population Variation Genetics: Experimental Strategies and Analysis 23.05.16 Norwic, UK More science events from Analysis Top Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations   pp117 - 125 Carlos L Araya, Can Cenik, Jason A Reuter, Gert Kiss, Vijay S Pande, Michael P Snyder & William J Greenleaf doi:10.1038/ng.3471 William Greenleaf, Michael Snyder, Carlos Araya and colleagues use density-based clustering methods on ~4,700 exomes from 21 tumor types to detect significantly mutated regions (SMRs), which show recurrent alterations in coding and noncoding elements and often associate with changes in gene expression and signaling. Mutation frequencies in SMRs demonstrate that distinct protein regions are differentially mutated across tumor types. Articles Top Timing, rates and spectra of human germline mutation   pp126 - 133 Raheleh Rahbari, Arthur Wuster, Sarah J Lindsay, Robert J Hardwick, Ludmil B Alexandrov, Saeed Al Turki, Anna Dominiczak, Andrew Morris, David Porteous, Blair Smith, Michael R Stratton, UK10K Consortium & Matthew E Hurles doi:10.1038/ng.3469 Matthew Hurles and colleagues sequence the genomes of three multi-sibling families and investigate the rates and spectra of germline mutation. Their analyses suggest that the mutation rate per cell division is higher during early embryogenesis than in post-pubertal spermatogenesis. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants   pp134 - 143 Lars G Fritsche, Wilmar Igl, Jessica N Cooke Bailey, Felix Grassmann, Sebanti Sengupta, Jennifer L Bragg-Gresham, Kathryn P Burdon, Scott J Hebbring, Cindy Wen, Mathias Gorski, Ivana K Kim, David Cho, Donald Zack, Eric Souied, Hendrik P N Scholl, Elisa Bala, Kristine E Lee, David J Hunter, Rebecca J Sardell, Paul Mitchell, Joanna E Merriam, Valentina Cipriani, Joshua D Hoffman, Tina Schick, Yara T E Lechanteur, Robyn H Guymer, Matthew P Johnson, Yingda Jiang, Chloe M Stanton, Gabriëlle H S Buitendijk, Xiaowei Zhan, Alan M Kwong, Alexis Boleda, Matthew Brooks, Linn Gieser, Rinki Ratnapriya, Kari E Branham, Johanna R Foerster, John R Heckenlively, Mohammad I Othman, Brendan J Vote, Helena Hai Liang, Emmanuelle Souzeau, Ian L McAllister, Timothy Isaacs, Janette Hall, Stewart Lake, David A Mackey, Ian J Constable, Jamie E Craig, Terrie E Kitchner, Zhenglin Yang, Zhiguang Su, Hongrong Luo, Daniel Chen, Hong Ouyang, Ken Flagg, Danni Lin, Guanping Mao, Henry Ferreyra, Klaus Stark, Claudia N von Strachwitz, Armin Wolf, Caroline Brandl, Guenther Rudolph, Matthias Olden, Margaux A Morrison, Denise J Morgan, Matthew Schu, Jeeyun Ahn, Giuliana Silvestri, Evangelia E Tsironi, Kyu Hyung Park, Lindsay A Farrer, Anton Orlin, Alexander Brucker, Mingyao Li, Christine A Curcio, Saddek Mohand-Saïd, José-Alain Sahel, Isabelle Audo, Mustapha Benchaboune, Angela J Cree, Christina A Rennie, Srinivas V Goverdhan, Michelle Grunin, Shira Hagbi-Levi, Peter Campochiaro, Nicholas Katsanis, Frank G Holz, Frédéric Blond, Hélène Blanché, Jean-François Deleuze, Robert P Igo Jr, Barbara Truitt, Neal S Peachey, Stacy M Meuer, Chelsea E Myers, Emily L Moore, Ronald Klein, Michael A Hauser, Eric A Postel, Monique D Courtenay, Stephen G Schwartz, Jaclyn L Kovach, William K Scott, Gerald Liew, Ava G Tan, Bamini Gopinath, John C Merriam, R Theodore Smith, Jane C Khan, Humma Shahid, Anthony T Moore, J Allie McGrath, Reneé Laux, Milam A Brantley Jr, Anita Agarwal, Lebriz Ersoy, Albert Caramoy, Thomas Langmann, Nicole T M Saksens, Eiko K de Jong, Carel B Hoyng, Melinda S Cain, Andrea J Richardson, Tammy M Martin, John Blangero, Daniel E Weeks, Bal Dhillon, Cornelia M van Duijn, Kimberly F Doheny, Jane Romm, Caroline C W Klaver, Caroline Hayward, Michael B Gorin, Michael L Klein, Paul N Baird, Anneke I den Hollander, Sascha Fauser, John R W Yates, Rando Allikmets, Jie Jin Wang, Debra A Schaumberg, Barbara E K Klein, Stephanie A Hagstrom, Itay Chowers, Andrew J Lotery, Thierry Léveillard, Kang Zhang, Murray H Brilliant, Alex W Hewitt, Anand Swaroop, Emily Y Chew, Margaret A Pericak-Vance, Margaret DeAngelis, Dwight Stambolian, Jonathan L Haines, Sudha K Iyengar, Bernhard H F Weber, Gonçalo R Abecasis & Iris M Heid doi:10.1038/ng.3448 Iris Heid, Goncalo Abecasis, Sudha Iyengar and colleagues report the results of a large genome-wide association meta-analysis of macular degeneration based on over 43,000 subjects. They identify 16 new risk loci, including some very rare coding variants. Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity   pp144 - 151 Nicole T M Saksens, Mark P Krebs, Frederieke E Schoenmaker-Koller, Wanda Hicks, Minzhong Yu, Lanying Shi, Lucy Rowe, Gayle B Collin, Jeremy R Charette, Stef J Letteboer, Kornelia Neveling, Tamara W van Moorsel, Sleiman Abu-Ltaif, Elfride De Baere, Sophie Walraedt, Sandro Banfi, Francesca Simonelli, Frans P M Cremers, Camiel J F Boon, Ronald Roepman, Bart P Leroy, Neal S Peachey, Carel B Hoyng, Patsy M Nishina & Anneke I den Hollander doi:10.1038/ng.3474 Anneke den Hollander, Patsy Nishina and colleagues report heterozygous missense mutations in CTNNA1 in three families with butterfly-shaped pigment dystrophy. Ctnna1-mutant mice display a similar phenotype and show increased cell shedding and large multinucleated cells in the retinal pigment epithelium, suggesting defects in intercellular adhesion and cytokinesis. Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses   pp152 - 158 Freyja Imsland, Kelly McGowan, Carl-Johan Rubin, Corneliu Henegar, Elisabeth Sundström, Jonas Berglund, Doreen Schwochow, Ulla Gustafson, Páll Imsland, Kerstin Lindblad-Toh, Gabriella Lindgren, Sofia Mikko, Lee Millon, Claire Wade, Mikkel Schubert, Ludovic Orlando, Maria Cecilia T Penedo, Gregory S Barsh & Leif Andersson doi:10.1038/ng.3475 Leif Andersson, Gregory Barsh and colleagues show that Dun camouflage color in horses is due to TBX3 expression in hair follicles, which causes asymmetric distribution of hair follicle melanocytes and reduced pigment deposition. They find that most domestic horses are more intensely pigmented (non-dun) owing to regulatory mutations impairing TBX3 expression in the hair follicle. MYB-FL controls gain and loss of floral UV absorbance, a key trait affecting pollinator preference and reproductive isolation   pp159 - 166 Hester Sheehan, Michel Moser, Ulrich Klahre, Korinna Esfeld, Alexandre Dell'Olivo, Therese Mandel, Sabine Metzger, Michiel Vandenbussche, Loreta Freitas & Cris Kuhlemeier doi:10.1038/ng.3462 Cris Kuhlemeier and colleagues analyze the genetic basis for floral UV absorbance in Petunia species with either nocturnal or diurnal pollinators. They show that distinct mutations in the MYB-FL gene explain gain or loss of UV absorbance that correlates with bee-to-moth and moth-to-hummingbird pollination transitions. See also: News and Views by Grotewold Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires OPEN   pp167 - 175 David Burstein, Francisco Amaro, Tal Zusman, Ziv Lifshitz, Ofir Cohen, Jack A Gilbert, Tal Pupko, Howard A Shuman & Gil Segal doi:10.1038/ng.3481 Gil Segal, Howard Shuman and colleagues sequence the genomes of 38 Legionella species and analyze 5,885 predicted effector proteins. Their analysis identifies a core set of seven effectors shared by all 38 species and numerous previously unidentified conserved effector domains. See also: News and Views by Comas Letters Top Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers   pp176 - 182 Xiaoyang Zhang, Peter S Choi, Joshua M Francis, Marcin Imielinski, Hideo Watanabe, Andrew D Cherniack & Matthew Meyerson doi:10.1038/ng.3470 Matthew Meyerson and colleagues identify focal amplifications of regions harboring super-enhancers near KLF5, USP12, PARD6B and MYC in epithelial cancers. CRISPR/Cas9-mediated repression or deletion of a MYC enhancer in a lung adenocarcinoma cell line with the enhancer amplification results in downregulation of MYC and its target genes and impaired anchorage-independent and clonogenic growth. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma   pp183 - 188 Jessica Okosun, Rachel L Wolfson, Jun Wang, Shamzah Araf, Lucy Wilkins, Brian M Castellano, Leire Escudero-Ibarz, Ahad Fahad Al Seraihi, Julia Richter, Stephan H Bernhart, Alejo Efeyan, Sameena Iqbal, Janet Matthews, Andrew Clear, José Afonso Guerra-Assunção, Csaba Bödör, Hilmar Quentmeier, Christopher Mansbridge, Peter Johnson, Andrew Davies, Jonathan C Strefford, Graham Packham, Sharon Barrans, Andrew Jack, Ming-Qing Du, Maria Calaminici, T Andrew Lister, Rebecca Auer, Silvia Montoto, John G Gribben, Reiner Siebert, Claude Chelala, Roberto Zoncu, David M Sabatini & Jude Fitzgibbon doi:10.1038/ng.3473 Jessica Okosun, David Sabatini and colleagues identify recurrent RRAGC mutations in follicular lymphoma, resulting in activated mTORC1 signaling. The activating nature of the mutations, their existence within the dominant clone and their stability during disease progression support the potential of these mutations as promising candidates for targeted therapy. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma   pp189 - 194 Jessica N Cooke Bailey, Stephanie J Loomis, Jae H Kang, R Rand Allingham, Puya Gharahkhani, Chiea Chuen Khor, Kathryn P Burdon, Hugues Aschard, Daniel I Chasman, Robert P Igo Jr, Pirro G Hysi, Craig A Glastonbury, Allison Ashley-Koch, Murray Brilliant, Andrew A Brown, Donald L Budenz, Alfonso Buil, Ching-Yu Cheng, Hyon Choi, William G Christen, Gary Curhan, Immaculata De Vivo, John H Fingert, Paul J Foster, Charles Fuchs, Douglas Gaasterland, Terry Gaasterland, Alex W Hewitt, Frank Hu, David J Hunter, Anthony P Khawaja, Richard K Lee, Zheng Li, Paul R Lichter, David A Mackey, Peter McGuffin, Paul Mitchell, Sayoko E Moroi, Shamira A Perera, Keating W Pepper, Qibin Qi, Tony Realini, Julia E Richards, Paul M Ridker, Eric Rimm, Robert Ritch, Marylyn Ritchie, Joel S Schuman, William K Scott, Kuldev Singh, Arthur J Sit, Yeunjoo E Song, Rulla M Tamimi, Fotis Topouzis, Ananth C Viswanathan, Shefali Setia Verma, Douglas Vollrath, Jie Jin Wang, Nicole Weisschuh, Bernd Wissinger, Gadi Wollstein, Tien Y Wong, Brian L Yaspan, Donald J Zack, Kang Zhang, EPIC-Norfolk Eye Study, ANZRAG Consortium, Robert N Weinreb, Margaret A Pericak-Vance, Kerrin Small, Christopher J Hammond, Tin Aung, Yutao Liu, Eranga N Vithana, Stuart MacGregor, Jamie E Craig, Peter Kraft, Gareth Howell, Michael A Hauser, Louis R Pasquale, Jonathan L Haines & Janey L Wiggs doi:10.1038/ng.3482 Janey Wiggs, Jonathan Haines and colleagues identify three new susceptibility loci for primary open-angle glaucoma. The association signals map near genes implicated in ocular development (FOXC1), neurodegeneration (ATXN2) and mitochondrial function (TXNRD2). Quantifying influenza virus diversity and transmission in humans   pp195 - 200 Leo L M Poon, Timothy Song, Roni Rosenfeld, Xudong Lin, Matthew B Rogers, Bin Zhou, Robert Sebra, Rebecca A Halpin, Yi Guan, Alan Twaddle, Jay V DePasse, Timothy B Stockwell, David E Wentworth, Edward C Holmes, Benjamin Greenbaum, Joseph S M Peiris, Benjamin J Cowling & Elodie Ghedin doi:10.1038/ng.3479 Elodie Ghedin, Benjamin Cowling and colleagues quantify the frequency at which variants of influenza virus were transmitted between individual hosts during the 2009 H1N1 pandemic in Hong Kong. They find transmission of multiple variants between donor-recipient pairs and provide estimates of the number of viral particles that can infect and replicate within a host. Hybridization of powdery mildew strains gives rise to pathogens on novel agricultural crop species OPEN   pp201 - 205 Fabrizio Menardo, Coraline R Praz, Stefan Wyder, Roi Ben-David, Salim Bourras, Hiromi Matsumae, Kaitlin E McNally, Francis Parlange, Andrea Riba, Stefan Roffler, Luisa K Schaefer, Kentaro K Shimizu, Luca Valenti, Helen Zbinden, Thomas Wicker & Beat Keller doi:10.1038/ng.3485 Beat Keller, Thomas Wicker and colleagues compare the genomes of 46 isolates of powdery mildew, Blumeria graminis. They find that B. graminis f. sp. triticale, a pathogen growing on triticale (a wheat × rye hybrid plant), is a hybrid of B. graminis f. sp. tritici and B. graminis f. sp. secalis, which grow on wheat and rye, respectively. See also: News and Views by Stukenbrock Technical Reports Top Fine-mapping cellular QTLs with RASQUAL and ATAC-seq   pp206 - 213 Natsuhiko Kumasaka, Andrew J Knights & Daniel J Gaffney doi:10.1038/ng.3467 Natsuhiko Kumasaka, Andrew Knights and Daniel Gaffney develop a new statistical approach for association mapping that models genetic effects and accounts for biases in sequencing data in a single probabilistic framework. They apply this method to generate a map of chromatin accessibility QTLs and show how it can be used to fine-map regulatory variants and link distal regulatory elements with genes. A spectral approach integrating functional genomic annotations for coding and noncoding variants   pp214 - 220 Iuliana Ionita-Laza, Kenneth McCallum, Bin Xu & Joseph D Buxbaum doi:10.1038/ng.3477 Iuliana Ionita-Laza, Kenneth McCallum and colleagues developed an unsupervised statistical approach, Eigen, that integrates different functional annotations into a single measure of functional importance for coding and noncoding variants. Their meta-score can outperform the recently proposed CADD score and can be applied to fine-mapping studies. Retraction Top Retraction: A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function   p221 Sonia A Melo, Santiago Ropero, Catia Moutinho, Lauri A Aaltonen, Hiroyuki Yamamoto, George A Calin, Simona Rossi, Agustin F Fernandez, Fatima Carneiro, Carla Oliveira, Bibiana Ferreira, Chang-Gong Liu, Alberto Villanueva, Gabriel Capella, Simo Schwartz Jr, Ramin Shiekhattar & Manel Esteller doi:10.1038/ng0216-221 Top 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

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