Nature Genetics Contents: May 2016 pp 475 - 586

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Advertisement Apply precision medicine to advance your clinical trial outcomes  Power your precision medicine clinical trials with genomic solutions  Download our complimentary precision medicine white paper now TABLE OF CONTENTS May 2016 Volume 48, Issue 5 Editorial News and Views Analysis Brief Communication Articles Letters Advertisement Japan is among the top producers of high quality research in the world, but new analysis using the Nature Index reveals this position is being challenged.  See the efforts being made to reverse this decline and how international collaborations are playing a role in the strategies of Japan's institutions. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Leena Peltonen School of Human Genomics (21-25 August 2016)  This summer school provides a unique opportunity to learn and be inspired by those that have shaped our understanding of human genomics in the past decade, and is suitable for scientists and clinicians undertaking graduate studies focused on human genetics and genomics. Application deadline: 17 May   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   Advertisement Don't miss the latest focus issues from Laboratory Investigation and Modern Pathology  Focus on Breast Highlighting recent advances in breast cancer diagnosis and treatment.  Focus on Soft Tissue Advancing understanding of the pathogenesis of soft tissue sarcomas, and describing advances that may lead to the development of new diagnostic tests and targeted therapies.     Editorial Top Regulatory networks in evolution   p475 doi:10.1038/ng.3566 Comparison of evolutionary adaptations and innovations illuminates the genetic basis for the development of animal forms. Gene networks that retain similar wiring diagrams in diverse and distantly related organisms point to the ways in which regulatory regions of the genome evolve. We may be close to being able to use comparative genomics to predict the evolvability of gene networks. News and Views Top Intolerable secretion and diabetes in tolerant transgenic mice, revisited   pp476 - 477 John A Todd doi:10.1038/ng.3560 A new mouse model linking diabetes, insulin secretion and autoimmunity with a high-fat diet supports a shared mechanism for type 1 (T1D) and type 2 (T2D) diabetes. In this model, the protein secretion system of insulin-producing pancreatic beta cells is stressed, leading to increased beta cell apoptosis and diabetes via reduced levels of the transcription factor GLIS3, a pathogenic pathway that can be mimicked by a high-fat diet. See also: Article by Dooley et al. Fat eggs shape offspring health   pp478 - 479 Erica D Watson & Joanna Rakoczy doi:10.1038/ng.3554 How maternal diet influences offspring metabolism is unclear, as it is difficult to distinguish between the effects of the in utero environment and epigenetic factors contributed by the oocyte. In a mouse model of high-fat diet, a new study teases apart these mechanisms by using in vitro fertilization and shows that susceptibility of offspring to metabolic disorder can likely be attributed to epigenetic inheritance via the oocyte. See also: Brief Communication by Huypens et al. Connecting the regulatory genome   pp479 - 480 John Stamatoyannopoulos doi:10.1038/ng.3553 Determining how the evolving genome-wide map of distal regulatory elements is connected with target genes has remained a significant challenge, despite progress in understanding chromatin architecture and regulation. A new study presents a computational approach for predicting distal element-gene interactions. See also: Analysis by Whalen et al. Genetics JOBS of the week NIH-Funded Postdoctoral Position in Imaging Genetics of Dystonia Icahn School of Medicine at Mount Sinai Gene Editing Core Manager St. Jude Children's Research Hospital (SJCRH) Postdoctoral Fellows in Statistical Genetics or Computational Biology Columbia University Senior Scientist - Chemical Genetics F. Hoffmann-La Roche AG Group leader Institut Curie More Science jobs from Genetics EVENT 8th Annual Next Generation Dx Summit 23.08.16 Washington DC, USA More science events from Analysis Top Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets   pp481 - 487 Zhihong Zhu, Futao Zhang, Han Hu, Andrew Bakshi, Matthew R Robinson, Joseph E Powell, Grant W Montgomery, Michael E Goddard, Naomi R Wray, Peter M Visscher & Jian Yang doi:10.1038/ng.3538 Jian Yang and colleagues propose a method that integrates summary data from GWAS and eQTL studies to identify genes whose expression levels are associated with complex traits because of pleiotropy. They apply the method to five human complex traits and prioritize 126 genes for future functional studies. Enhancer-promoter interactions are encoded by complex genomic signatures on looping chromatin   pp488 - 496 Sean Whalen, Rebecca M Truty & Katherine S Pollard doi:10.1038/ng.3539 Sean Whalen and colleagues present a computational method, TargetFinder, for reconstructing three-dimensional regulatory landscapes using one-dimensional genomic features. TargetFinder identifies the minimal set of features necessary to predict individual interacting enhancer-promoter pairs and accurately distinguishes them from non-interacting pairs. See also: News and Views by Stamatoyannopoulos Brief Communication Top Epigenetic germline inheritance of diet-induced obesity and insulin resistance   pp497 - 499 Peter Huypens, Steffen Sass, Moya Wu, Daniela Dyckhoff, Matthias Tschöp, Fabian Theis, Susan Marschall, Martin Hrabě de Angelis & Johannes Beckers doi:10.1038/ng.3527 Johannes Beckers, Martin Hrabě de Angelis and colleagues use in vitro fertilization to demonstrate epigenetic germline inheritance of acquired metabolic disorders in mice. They show that a parental high-fat diet renders offspring more susceptible to developing obesity and diabetes. See also: News and Views by Watson & Rakoczy Advertisement nature.com webcasts Nature Publishing Group presents a custom webcast on: Overcoming the challenges of NGS-based RNA profiling using limited, precious samples Tuesday May 10, 2016 at 9AM PDT, 12PM EDT, 5PM BST, 6PM CEST Register for the webcast and live Q&A session Sponsored by: HTG Molecular Diagnostics     Articles Top Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer   pp500 - 509 Akihiro Fujimoto, Mayuko Furuta, Yasushi Totoki, Tatsuhiko Tsunoda, Mamoru Kato, Yuichi Shiraishi, Hiroko Tanaka, Hiroaki Taniguchi, Yoshiiku Kawakami, Masaki Ueno, Kunihito Gotoh, Shun-ichi Ariizumi, Christopher P Wardell, Shinya Hayami, Toru Nakamura, Hiroshi Aikata, Koji Arihiro, Keith A Boroevich, Tetsuo Abe, Kaoru Nakano, Kazuhiro Maejima, Aya Sasaki-Oku, Ayako Ohsawa, Tetsuo Shibuya, Hiromi Nakamura, Natsuko Hama, Fumie Hosoda, Yasuhito Arai, Shoko Ohashi, Tomoko Urushidate, Genta Nagae, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Hidenori Ojima, Nobuyoshi Hiraoka, Takuji Okusaka, Michiaki Kubo, Shigeru Marubashi, Terumasa Yamada, Satoshi Hirano, Masakazu Yamamoto, Hideki Ohdan, Kazuaki Shimada, Osamu Ishikawa, Hiroki Yamaue, Kazuki Chayama, Satoru Miyano, Hiroyuki Aburatani, Tatsuhiro Shibata & Hidewaki Nakagawa doi:10.1038/ng.3547 Hidewaki Nakagawa and colleagues report a comprehensive genome-wide mutational landscape of 300 liver cancers from Japanese individuals. They identify candidate driver mutations, including ones in noncoding regions, and structural mutations affecting the expression of nearby genes. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci   pp510 - 518 David Ellinghaus, Luke Jostins, Sarah L Spain, Adrian Cortes, Jörn Bethune, Buhm Han, Yu Rang Park, Soumya Raychaudhuri, Jennie G Pouget, Matthias Hübenthal, Trine Folseraas, Yunpeng Wang, Tonu Esko, Andres Metspalu, Harm-Jan Westra, Lude Franke, Tune H Pers, Rinse K Weersma, Valerie Collij, Mauro D'Amato, Jonas Halfvarson, Anders Boeck Jensen, Wolfgang Lieb, Franziska Degenhardt, Andreas J Forstner, Andrea Hofmann, The International IBD Genetics Consortium (IIBDGC), International Genetics of Ankylosing Spondylitis Consortium (IGAS), International PSC Study Group (IPSCSG), Genetic Analysis of Psoriasis Consortium (GAPC), Psoriasis Association Genetics Extension (PAGE), Stefan Schreiber, Ulrich Mrowietz, Brian D Juran, Konstantinos N Lazaridis, Søren Brunak, Anders M Dale, Richard C Trembath, Stephan Weidinger, Michael Weichenthal, Eva Ellinghaus, James T Elder, Jonathan N W N Barker, Ole A Andreassen, Dermot P McGovern, Tom H Karlsen, Jeffrey C Barrett, Miles Parkes, Matthew A Brown & Andre Franke doi:10.1038/ng.3528 David Ellinghaus and colleagues report a combined association analysis of five chronic inflammatory diseases. They identify 27 new associations and highlight disease-specific association patterns at shared susceptibility loci. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes   pp519 - 527 James Dooley, Lei Tian, Susann Schonefeldt, Viviane Delghingaro-Augusto, Josselyn E Garcia-Perez, Emanuela Pasciuto, Daniele Di Marino, Edward J Carr, Nikolay Oskolkov, Valeriya Lyssenko, Dean Franckaert, Vasiliki Lagou, Lut Overbergh, Jonathan Vandenbussche, Joke Allemeersch, Genevieve Chabot-Roy, Jane E Dahlstrom, D Ross Laybutt, Nikolai Petrovsky, Luis Socha, Kris Gevaert, Anton M Jetten, Diether Lambrechts, Michelle A Linterman, Chris C Goodnow, Christopher J Nolan, Sylvie Lesage, Susan M Schlenner & Adrian Liston doi:10.1038/ng.3531 Adrian Liston and colleagues use a transgenic mouse model to demonstrate that beta cell failure is a mechanistic commonality in type 1 and type 2 diabetes. They find that the changes in the molecular pathways identified as contributing to beta cell loss are paralleled in human islets from patients with type 2 diabetes. See also: News and Views by Todd Transcriptomic and epigenomic characterization of the developing bat wing OPEN   pp528 - 536 Walter L Eckalbar, Stephen A Schlebusch, Mandy K Mason, Zoe Gill, Ash V Parker, Betty M Booker, Sierra Nishizaki, Christiane Muswamba-Nday, Elizabeth Terhune, Kimberly A Nevonen, Nadja Makki, Tara Friedrich, Julia E VanderMeer, Katherine S Pollard, Lucia Carbone, Jeff D Wall, Nicola Illing & Nadav Ahituv doi:10.1038/ng.3537 Nadav Ahituv, Nicola Illing, Jeff Wall and colleagues sequence the genome of the bat Miniopterus natalensis and perform RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages. Their analyses identify genomic regions that may contribute to bat wing formation. Genetic lineage tracing identifies endocardial origin of liver vasculature   pp537 - 543 Hui Zhang, Wenjuan Pu, Xueying Tian, Xiuzhen Huang, Lingjuan He, Qiaozhen Liu, Yan Li, Libo Zhang, Liang He, Kuo Liu, Astrid Gillich & Bin Zhou doi:10.1038/ng.3536 Bin Zhou and colleagues use genetic labeling in mice to show that endocardial cells of the sinus venosus substantially contribute to the liver vasculature, which thus shares a common developmental origin with coronary arteries. Inhibition of endocardial angiogenesis leads to reduced endocardial contribution to the liver vasculature and to defects in liver organogenesis. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance   pp544 - 551 Christopher A Desjardins, Keira A Cohen, Vanisha Munsamy, Thomas Abeel, Kashmeel Maharaj, Bruce J Walker, Terrance P Shea, Deepak V Almeida, Abigail L Manson, Alex Salazar, Nesri Padayatchi, Max R O'Donnell, Koleka P Mlisana, Jennifer Wortman, Bruce W Birren, Jacques Grosset, Ashlee M Earl & Alexander S Pym doi:10.1038/ng.3548 Alexander Pym, Ashlee Earl and colleagues use the whole-genome sequences from 498 strains of Mycobacterium tuberculosis to identify new genotypes conferring resistance to antitubercular drugs. They find that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, are associated with unexplained drug resistance and demonstrate that these mutations confer resistance to D-cycloserine. 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Find out how   Letters Top Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population   pp552 - 555 Elise B Robinson, Beate St Pourcain, Verneri Anttila, Jack A Kosmicki, Brendan Bulik-Sullivan, Jakob Grove, Julian Maller, Kaitlin E Samocha, Stephan J Sanders, Stephan Ripke, Joanna Martin, Mads V Hollegaard, Thomas Werge, David M Hougaard, iPSYCH-SSI-Broad Autism Group, Benjamin M Neale, David M Evans, David Skuse, Preben Bo Mortensen, Anders D Børglum, Angelica Ronald, George Davey Smith & Mark J Daly doi:10.1038/ng.3529 Elise Robinson, Mark Daly and colleagues present an analysis of genetic data from autism spectrum disorder (ASD) and population-based studies and find evidence for genetic correlations between ASDs and typical variation in social behavior and communication traits. These results may inform genetic models of ASDs and other neuropsychiatric disorders. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma   pp556 - 562 Chiea Chuen Khor, Tan Do, Hongyan Jia, Masakazu Nakano, Ronnie George, Khaled Abu-Amero, Roopam Duvesh, Li Jia Chen, Zheng Li, Monisha E Nongpiur, Shamira A Perera, Chunyan Qiao, Hon-Tym Wong, Hiroshi Sakai, Mônica Barbosa de Melo, Mei-Chin Lee, Anita S Chan, Yaakub Azhany, Thi Lam Huong Dao, Yoko Ikeda, Rodolfo A Perez-Grossmann, Tomasz Zarnowski, Alexander C Day, Jost B Jonas, Pancy O S Tam, Tuan Anh Tran, Humaira Ayub, Farah Akhtar, Shazia Micheal, Paul T K Chew, Leyla A Aljasim, Tanuj Dada, Tam Thi Luu, Mona S Awadalla, Naris Kitnarong, Boonsong Wanichwecharungruang, Yee Yee Aung, Jelinar Mohamed-Noor, Saravanan Vijayan, Sripriya Sarangapani, Rahat Husain, Aliza Jap, Mani Baskaran, David Goh, Daniel H Su, Huaizhou Wang, Vernon K Yong, Leonard W Yip, Tuyet Bach Trinh, Manchima Makornwattana, Thanh Thu Nguyen, Edgar U Leuenberger, Ki-Ho Park, Widya Artini Wiyogo, Rajesh S Kumar, Celso Tello, Yasuo Kurimoto, Suman S Thapa, Kessara Pathanapitoon, John F Salmon, Yong Ho Sohn, Antonio Fea, Mineo Ozaki, Jimmy S M Lai, Visanee Tantisevi, Chaw Chaw Khaing, Takanori Mizoguchi, Satoko Nakano, Chan-Yun Kim, Guangxian Tang, Sujie Fan, Renyi Wu, Hailin Meng, Thi Thuy Giang Nguyen, Tien Dat Tran, Morio Ueno, Jose Maria Martinez, Norlina Ramli, Yin Mon Aung, Rigo Daniel Reyes, Stephen A Vernon, Seng Kheong Fang, Zhicheng Xie, Xiao Yin Chen, Jia Nee Foo, Kar Seng Sim, Tina T Wong, Desmond T Quek, Rengaraj Venkatesh, Srinivasan Kavitha, Subbiah R Krishnadas, Nagaswamy Soumittra, Balekudaru Shantha, Boon-Ang Lim, Jeanne Ogle, José P C de Vasconcellos, Vital P Costa, Ricardo Y Abe, Bruno B de Souza, Chelvin C Sng, Maria C Aquino, Ewa Kosior-Jarecka, Guillermo Barreto Fong, Vania Castro Tamanaja, Ricardo Fujita, Yuzhen Jiang, Naushin Waseem, Sancy Low, Huan Nguyen Pham, Sami Al-Shahwan, E Randy Craven, Muhammad Imran Khan, Rrima Dada, Kuldeep Mohanty, Muneeb A Faiq, Alex W Hewitt, Kathryn P Burdon, Eng Hui Gan, Anuwat Prutthipongsit, Thipnapa Patthanathamrongkasem, Mary Ann T Catacutan, Irene R Felarca, Chona S Liao, Emma Rusmayani, Vira Wardhana Istiantoro, Giulia Consolandi, Giulia Pignata, Carlo Lavia, Prin Rojanapongpun, Lerprat Mangkornkanokpong, Sunee Chansangpetch, Jonathan C H Chan, Bonnie N K Choy, Jennifer W H Shum, Hlaing May Than, Khin Thida Oo, Aye Thi Han, Victor H Yong, Xiao-Yu Ng, Shuang Ru Goh, Yaan Fun Chong, Martin L Hibberd, Mark Seielstad, Eileen Png, Sarah J Dunstan, Nguyen Van Vinh Chau, Jinxin Bei, Yi Xin Zeng, Abhilasha Karkey, Buddha Basnyat, Francesca Pasutto, Daniela Paoli, Paolo Frezzotti, Jie Jin Wang, Paul Mitchell, John H Fingert, R Rand Allingham, Michael A Hauser, Soon Thye Lim, Soo Hong Chew, Richard P Ebstein, Anavaj Sakuntabhai, Kyu Hyung Park, Jeeyun Ahn, Greet Boland, Harm Snippe, Richard Stead, Raquel Quino, Su Nyunt Zaw, Urszula Lukasik, Rohit Shetty, Mimiwati Zahari, Hyoung Won Bae, Nay Lin Oo, Toshiaki Kubota, Anita Manassakorn, Wing Lau Ho, Laura Dallorto, Young Hoon Hwang, Christine A Kiire, Masako Kuroda, Zeiras Eka Djamal, Jovell Ian M Peregrino, Arkasubhra Ghosh, Jin Wook Jeoung, Tung S Hoan, Nuttamon Srisamran, Thayanithi Sandragasu, Saw Htoo Set, Vi Huyen Doan, Shomi S Bhattacharya, Ching-Lin Ho, Donald T Tan, Ramanjit Sihota, Seng-Chee Loon, Kazuhiko Mori, Shigeru Kinoshita, Anneke I den Hollander, Raheel Qamar, Ya-Xing Wang, Yik Y Teo, E-Shyong Tai, Curt Hartleben-Matkin, David Lozano-Giral, Seang Mei Saw, Ching-Yu Cheng, Juan C Zenteno, Chi Pui Pang, Huong T T Bui, Owen Hee, Jamie E Craig, Deepak P Edward, Michiko Yonahara, Jamil Miguel Neto, Maria L Guevara-Fujita, Liang Xu, Robert Ritch, Ahmad Tajudin Liza-Sharmini, Tien Y Wong, Saleh Al-Obeidan, Nhu Hon Do, Periasamy Sundaresan, Clement C Tham, Paul J Foster, Lingam Vijaya, Kei Tashiro, Eranga N Vithana, Ningli Wang & Tin Aung doi:10.1038/ng.3540 Chiea Chuen Khor, Tin Aung and colleagues report the results of a large genome-wide association study of primary angle closure glaucoma. They identify five new susceptibility loci and provide insights into disease pathogenesis. Mosaic loss of chromosome Y is associated with common variation near TCL1A   pp563 - 568 Weiyin Zhou, Mitchell J Machiela, Neal D Freedman, Nathaniel Rothman, Nuria Malats, Casey Dagnall, Neil Caporaso, Lauren T Teras, Mia M Gaudet, Susan M Gapstur, Victoria L Stevens, Kevin B Jacobs, Joshua Sampson, Demetrius Albanes, Stephanie Weinstein, Jarmo Virtamo, Sonja Berndt, Robert N Hoover, Amanda Black, Debra Silverman, Jonine Figueroa, Montserrat Garcia-Closas, Francisco X Real, Julie Earl, Gaelle Marenne, Benjamin Rodriguez-Santiago, Margaret Karagas, Alison Johnson, Molly Schwenn, Xifeng Wu, Jian Gu, Yuanqing Ye, Amy Hutchinson, Margaret Tucker, Luis A Perez-Jurado, Michael Dean, Meredith Yeager & Stephen J Chanock doi:10.1038/ng.3545 Meredith Yeager, Stephen Chanock and colleagues analyze mosaic loss of the Y chromosome in three prospective cohorts and observe association with age and smoking but not with cancer survival. They also identify common variation at TCL1A associated with increased risk of mosaic loss of the Y chromosome. Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults   pp569 - 574 Takahiko Yasuda, Shinobu Tsuzuki, Masahito Kawazu, Fumihiko Hayakawa, Shinya Kojima, Toshihide Ueno, Naoto Imoto, Shinji Kohsaka, Akiko Kunita, Koichiro Doi, Toru Sakura, Toshiaki Yujiri, Eisei Kondo, Katsumichi Fujimaki, Yasunori Ueda, Yasutaka Aoyama, Shigeki Ohtake, Junko Takita, Eirin Sai, Masafumi Taniwaki, Mineo Kurokawa, Shinichi Morishita, Masashi Fukayama, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe & Hiroyuki Mano doi:10.1038/ng.3535 Hiroyuki Mano and colleagues report fusions involving DUX4 in 16.4% of Ph-negative adolescent and young adult acute lymphoblastic leukemia (AYA-ALL) cases. Transplantation assays in mice support an oncogenic role for the DUX4-IGH fusion gene, which expresses DUX4 protein with an aberrant C terminus at high levels in patients with AYA-ALL. Cis-regulatory architecture of a brain signaling center predates the origin of chordates   pp575 - 580 Yao Yao, Paul J Minor, Ying-Tao Zhao, Yongsu Jeong, Ariel M Pani, Anna N King, Orsolya Symmons, Lin Gan, Wellington V Cardoso, François Spitz, Christopher J Lowe & Douglas J Epstein doi:10.1038/ng.3542 Douglas Epstein and colleagues use de novo motif analysis to identify sequence motifs and cognate transcription factors for brain enhancers of Shh active in the zona limitans intrathalamica (zli). They find new zli enhancers in mice and a functional equivalent in hemichordates, indicating an ancient origin of these sequence elements. A role for the bacterial GATC methylome in antibiotic stress survival   pp581 - 586 Nadia R Cohen, Christian A Ross, Saloni Jain, Rebecca S Shapiro, Arnaud Gutierrez, Peter Belenky, Hu Li & James J Collins doi:10.1038/ng.3530 James Collins and colleagues explore the role of the bacterial epigenome in antibiotic stress survival. They find that Escherichia coli survival under antibiotic pressure is strongly compromised in the absence of adenine methylation at GATC sites, suggesting that targeting adenine methylation might be a viable approach to enhance antibiotic activity. Top Advertisement npj Molecular Phenomics is a new open access journal now open for submissions. The journal encourages studies that integrate diverse phenotyping approaches to understand the molecular aspects of phenomes.  Sign up for e-alerts   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. 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