Nature Genetics Contents: July 2012 pp 733 - 831

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EA will help you detect 2x more differentially expressed transcripts, novel isoforms and SNVs and can achieve >97% alignment. 919-405-2248 * 866-293-6094 Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Epigenomics of Common Diseases (12-15 October 2012) Johns Hopkins University, USA This 2nd Wellcome Trust Epigenomics of Common Diseases conference will bring together scientists from the fields of epigenomics, genetics and bioinformatics to discuss how changes in the epigenome influence the development of common disease. Abstracts due by 27 July. Register by 1 September.   Advertisement Scientific Reports publishes 457 open access papers in its first year Publishing technically sound research articles, Scientific Reports is Nature Publishing Group’s fastest growing journal. Given the speed and visibility offered, no wonder 93% of our authors said that they are “likely” or “very likely” to submit again. Keep your research moving. Submit to Scientific Reports   Editorial Top Asking for more   p733 doi:10.1038/ng.2345 Because of the usefulness of genome-wide association study (GWAS) data for mapping regulatory variation in the human genome, the journal now asks authors to report the co-location of trait-associated variants with gene regulatory elements identified by epigenetic, functional and conservation criteria. We also ask that authors publish or database the genotype frequencies or association P values for all SNPs investigated, whether or not they reached genome-wide significance. News and Views Top A crop of maize variants   pp734 - 735 Xuehui Huang and Bin Han doi:10.1038/ng.2326 Three new studies report large-scale resequencing and comparative genomic analysis of diverse maize varieties. The authors conducted a comprehensive characterization of sequence variation in maize genomes and identified signals of selection in maize domestication and breeding. See also: Letter by Chia et al. | Letter by Hufford et al. | Letter by Jiao et al. Tuning gene expression with nucleosome-disfavoring sequences   pp735 - 736 Timothy Palpant and Jason Lieb doi:10.1038/ng.2328 A new study shows that alteration of poly(dA:dT) tracts in promoters offers a broadly applicable genetic mechanism for predictably tuning gene expression with high resolution. By systematically manipulating these tracts in a controlled yeast system, the authors demonstrate quantitative mechanistic relationships linking regulatory DNA sequences, nucleosome occupancy, transcription factor binding and gene expression. See also: Article by Raveh-Sadka et al. Gain of function in CDKN1C   pp737 - 738 Andrea Riccio and Maria Vittoria Cubellis doi:10.1038/ng.2336 Loss-of-function mutations in the gene encoding the cyclin-dependent kinase inhibitor CDKN1C cause Beckwith-Wiedemann syndrome and cancer. A new study now identifies potentially gain-of-function missense mutations in CDKN1C that cause the undergrowth-associated IMAGe syndrome. See also: Letter by Arboleda et al. Genetics JOBS of the week Post-doctoral position in Plant Genetics French National Institute for Agricultural Research (INRA) Research worker in the Laboratory of Molecular, Cellular and Quantitative Genetics The University of South Bohemia in Ceske Budejovice, The Faculty of Fisheries and Protection of Waters postdoc in Genetics Dept. Biochemistry and Molecular Biology, University of Gothenburg Microbiology and Molecular Genetics Faculty positions The University of Texas Health Science Center at Houston Chair - Department of Human Genetics McGill University More Science jobs from Genetics EVENT Yeast Genetics and Genomics 24.07.-13.08.12 US More science events from Research Highlights Top Hypermutation in breast cancer | Targeting cancer stem cells | STAT3 activation in rare T-cell leukemia | Mapping 5-hydroxylmethylcytosine | Rare variation in human populations Brief Communication Top Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency   pp740 - 742 Eirini Meimaridou, Julia Kowalczyk, Leonardo Guasti, Claire R Hughes, Florian Wagner, Peter Frommolt, Peter Nürnberg, Nicholas P Mann, Ritwik Banerjee, H Nurcin Saka, J Paul Chapple, Peter J King, Adrian J L Clark & Louise A Metherell doi:10.1038/ng.2299 Adrian Clark and colleagues report mutations in the NNT gene encoding nicotinamide nucleotide transhydrogenase in familial glucocorticoid deficiency (FGD). Advertisement Human and Mouse Exome NGS from $698, guaranteed coverage RNA-Seq from $698 with guaranteed reads 4-6 wks fastest turnaround time in the industry http://www.otogenetics.com/   Articles Top Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast   pp743 - 750 Tali Raveh-Sadka, Michal Levo, Uri Shabi, Boaz Shany, Leeat Keren, Maya Lotan-Pompan, Danny Zeevi, Eilon Sharon, Adina Weinberger and Eran Segal doi:10.1038/ng.2305 Eran Segal and colleagues measure the promoter activities of 70 different constructed promoter variants and find that poly(dA:dT) tracts significantly affect transcriptional outcome. They suggest that this is mediated by altering nucleosome organization and that these sequences can be manipulated to fine tune regulation of gene expression. See also: News and Views by Palpant & Lieb BAP1 loss defines a new class of renal cell carcinoma   pp751 - 759 Samuel Peña-Llopis, Silvia Vega-Rubín-de-Celis, Arnold Liao, Nan Leng, Andrea Pavía-Jiménez, Shanshan Wang, Toshinari Yamasaki, Leah Zhrebker, Sharanya Sivanand, Patrick Spence, Lisa Kinch, Tina Hambuch, Suneer Jain, Yair Lotan, Vitaly Margulis, Arthur I Sagalowsky, Pia Banerji Summerour, Wareef Kabbani, S W Wendy Wong, Nick Grishin, Marc Laurent, Xian-Jin Xie, Christian D Haudenschild, Mark T Ross, David R Bentley, Payal Kapur & James Brugarolas doi:10.1038/ng.2323 James Brugarolas and colleagues identify recurrent BAP1 mutations in clear cell renal cell carcinoma (ccRCC). They show that BAP1 binds to HCF-1 and suppresses cell proliferation, and they find that BAP1 loss is associated with high tumor grade. Letters Top Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators   pp760 - 764 Akihiro Fujimoto, Yasushi Totoki, Tetsuo Abe, Keith A Boroevich, Fumie Hosoda, Ha Hai Nguyen, Masayuki Aoki, Naoya Hosono, Michiaki Kubo, Fuyuki Miya, Yasuhito Arai, Hiroyuki Takahashi, Takuya Shirakihara, Masao Nagasaki, Tetsuo Shibuya, Kaoru Nakano, Kumiko Watanabe-Makino, Hiroko Tanaka, Hiromi Nakamura, Jun Kusuda, Hidenori Ojima, Kazuaki Shimada, Takuji Okusaka, Masaki Ueno, Yoshinobu Shigekawa, Yoshiiku Kawakami, Koji Arihiro, Hideki Ohdan, Kunihito Gotoh, Osamu Ishikawa, Shun-ichi Ariizumi, Masakazu Yamamoto, Terumasa Yamada, Kazuaki Chayama, Tomoo Kosuge, Hiroki Yamaue, Naoyuki Kamatani, Satoru Miyano, Hitoshi Nakagama, Yusuke Nakamura, Tatsuhiko Tsunoda, Tatsuhiro Shibata & Hidewaki Nakagawa doi:10.1038/ng.2291 Hidewaki Nakagawa and colleagues report the whole-genome sequencing of 27 hepatocellular carcinomas. They find that chromatin regulators were mutated in approximately 50% of tumors. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma   pp765 - 769 Wing-Kin Sung, Hancheng Zheng, Shuyu Li, Ronghua Chen, Xiao Liu, Yingrui Li, Nikki P Lee, Wah H Lee, Pramila N Ariyaratne, Chandana Tennakoon, Fabianus H Mulawadi, Kwong F Wong, Angela M Liu, Ronnie T Poon, Sheung Tat Fan, Kwong L Chan, Zhuolin Gong, Yujie Hu, Zhao Lin, Guan Wang, Qinghui Zhang, Thomas D Barber, Wen-Chi Chou, Amit Aggarwal, Ke Hao, Wei Zhou, Chunsheng Zhang, James Hardwick, Carolyn Buser, Jiangchun Xu, Zhengyan Kan, Hongyue Dai, Mao Mao, Christoph Reinhard, Jun Wang & John M Luk doi:10.1038/ng.2295 John Luk and colleagues report the sequencing of 81 hepatitis B virus (HBV)-positive and 7 HBV-negative hepatocellular carcinomas and matched normal tissues. They confirm recurrent integration events of HBV at TERT and MLL4 and report recurrent events at the CCNE1 gene. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk   pp770 - 776 Malcolm G Dunlop, Sara E Dobbins, Susan Mary Farrington, Angela M Jones, Claire Palles, Nicola Whiffin, Albert Tenesa, Sarah Spain, Peter Broderick, Li-Yin Ooi, Enric Domingo, Claire Smillie, Marc Henrion, Matthew Frampton, Lynn Martin, Graeme Grimes, Maggie Gorman, Colin Semple, Yusanne P Ma, Ella Barclay, James Prendergast, Jean-Baptiste Cazier, Bianca Olver, Steven Penegar, Steven Lubbe, Ian Chander, Luis G Carvajal-Carmona, Stephane Ballereau, Amy Lloyd, Jayaram Vijayakrishnan, Lina Zgaga, Igor Rudan, Evropi Theodoratou, The Colorectal Tumour Gene Identification (CORGI) Consortium, John M Starr, Ian Deary, Iva Kirac, Dujo Kovacević, Lauri A Aaltonen, Laura Renkonen-Sinisalo, Jukka-Pekka Mecklin, Koichi Matsuda, Yusuke Nakamura, Yukinori Okada, Steven Gallinger, David J Duggan, David Conti, Polly Newcomb, John Hopper, Mark A Jenkins, Fredrick Schumacher, Graham Casey, Douglas Easton, Mitul Shah, Paul Pharoah, Annika Lindblom, Tao Liu, The Swedish Low-Risk Colorectal Cancer Study Group, Christopher G Smith, Hannah West, Jeremy P Cheadle, The COIN Collaborative Group, Rachel Midgley, David J Kerr, Harry Campbell, Ian P Tomlinson & Richard S Houlston doi:10.1038/ng.2293 Richard Houlston and colleagues report a genome-wide association study for colorectal cancer. They report three loci newly associated with colorectal cancer, bringing the total number of common susceptibility loci to 20. Genome-wide association analysis identifies susceptibility loci for migraine without aura   pp777 - 782 Tobias Freilinger, Verneri Anttila, Boukje de Vries, Rainer Malik, Mikko Kallela, Gisela M Terwindt, Patricia Pozo-Rosich, Bendik Winsvold, Dale R Nyholt, Willebrordus P J van Oosterhout, Ville Artto, Unda Todt, Eija Hämäläinen, Jèssica Fernández-Morales, Mark A Louter, Mari A Kaunisto, Jean Schoenen, Olli Raitakari, Terho Lehtimäki, Marta Vila-Pueyo, Hartmut Göbel, Erich Wichmann, Cèlia Sintas, Andre G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Axel Heinze, Erling Tronvik, Cornelia M van Duijn, Jaakko Kaprio, Bru Cormand, Maija Wessman, Rune R Frants, Thomas Meitinger, Bertram Müller-Myhsok, John-Anker Zwart, Markus Färkkilä, Alfons Macaya, Michel D Ferrari, Christian Kubisch, Aarno Palotie, Martin Dichgans, Arn M J M van den Maagdenberg & International Headache Genetics Consortium doi:10.1038/ng.2307 Arn van den Maagdenberg and colleagues report a genome-wide association analysis for migraine without aura, the most common form of migraine. They identify two loci that are newly associated with migraine without aura. Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome   pp783 - 787 Leopold Groesser, Eva Herschberger, Arno Ruetten, Claudia Ruivenkamp, Enrico Lopriore, Markus Zutt, Thomas Langmann, Sebastian Singer, Laura Klingseisen, Wulf Schneider-Brachert, Agusti Toll, Francisco X Real, Michael Landthaler & Christian Hafner doi:10.1038/ng.2316 Christian Hafner and colleagues identify postzygotic HRAS and KRAS mutations as the cause of nevus sebaceous and Schimmelpenning syndrome. Their functional studies suggest that the HRAS p.Gly13Arg alteration, found in 91% of lesions, results in activation of the MAPK and PI3K-Akt signaling pathways. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome   pp788 - 792 Valerie A Arboleda, Hane Lee, Rahul Parnaik, Alice Fleming, Abhik Banerjee, Bruno Ferraz-de-Souza, Emmanuèle C Délot, Imilce A Rodriguez-Fernandez, Debora Braslavsky, Ignacio Bergadá, Esteban C Dell'Angelica, Stanley F Nelson, Julian A Martinez-Agosto, John C Achermann & Eric Vilain doi:10.1038/ng.2275 Eric Vilain and colleagues identify missense mutations in the imprinted gene CDKN1C, encoding the p57KIP2 cyclin dependent kinase inhibitor, in individuals with IMAGe syndrome. IMAGe syndrome is a developmental disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies. See also: News and Views by Riccio & Cubellis Dominant missense mutations in ABCC9 cause Cantu syndrome   pp793 - 796 Magdalena Harakalova, Jeske J T van Harssel, Paulien A Terhal, Stef van Lieshout, Karen Duran, Ivo Renkens, David J Amor, Louise C Wilson, Edwin P Kirk, Claire L S Turner, Debbie Shears, Sixto Garcia-Minaur, Melissa M Lees, Alison Ross, Hanka Venselaar, Gert Vriend, Hiroki Takanari, Martin B Rook, Marcel A G van der Heyden, Folkert W Asselbergs, Hans M Breur, Marielle E Swinkels, Ingrid J Scurr, Sarah F Smithson, Nine V Knoers, Jasper J van der Smagt, Isaac J Nijman, Wigard P Kloosterman, Mieke M van Haelst, Gijs van Haaften & Edwin Cuppen doi:10.1038/ng.2324 Edwin Cuppen, Gijs van Haaften and colleagues report the identification of mutations in ABCC9 in individuals with Cantu syndrome, which is characterized by congenital hypertrichosis, distinctive facial features, cardiomegaly and osteochondrodyplasia. ABCC9 encodes an ATP-dependent potassium channel. Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness   pp797 - 802 Saskia B Wortmann, Frédéric M Vaz, Thatjana Gardeitchik, Lisenka E L M Vissers, G Herma Renkema, Janneke H M Schuurs-Hoeijmakers, Wim Kulik, Martin Lammens, Christin Christin, Leo A J Kluijtmans, Richard J Rodenburg, Leo G J Nijtmans, Anne Grünewald, Christine Klein, Joachim M Gerhold, Tamas Kozicz, Peter M van Hasselt, Magdalena Harakalova, Wigard Kloosterman, Ivo Barić, Ewa Pronicka, Sema Kalkan Ucar, Karin Naess, Kapil K Singhal, Zita Krumina, Christian Gilissen, Hans van Bokhoven, Joris A Veltman, Jan A M Smeitink, Dirk J Lefeber, Johannes N Spelbrink, Ron A Wevers, Eva Morava & Arjan P M de Brouwer doi:10.1038/ng.2325 Ron Wevers, Saskia Wortmann and colleagues show that mutations in SERAC1 cause a recessive syndrome characterized by deafness, encephalopathy, progressive spasticity and dystonia. Their findings suggest a role for SERAC1 in phosphatidylglycerol remodeling and intracellular cholesterol trafficking. Maize HapMap2 identifies extant variation from a genome in flux   pp803 - 807 Jer-Ming Chia, Chi Song, Peter J Bradbury, Denise Costich, Natalia de Leon, John Doebley, Robert J Elshire, Brandon Gaut, Laura Geller, Jeffrey C Glaubitz, Michael Gore, Kate E Guill, Jim Holland, Matthew B Hufford, Jinsheng Lai, Meng Li, Xin Liu, Yanli Lu, Richard McCombie, Rebecca Nelson, Jesse Poland, Boddupalli M Prasanna, Tanja Pyhäjärvi, Tingzhao Rong, Rajandeep S Sekhon, Qi Sun, Maud I Tenaillon, Feng Tian, Jun Wang, Xun Xu, Zhiwu Zhang, Shawn M Kaeppler, Jeffrey Ross-Ibarra, Michael D McMullen, Edward S Buckler, Gengyun Zhang, Yunbi Xu & Doreen Ware doi:10.1038/ng.2313 The nucleotide diversity present in maize exceeds that in humans by an order of magnitude, and it has been challenging to characterize the high levels of diversity in this important crop. Doreen Ware and colleagues have identified 55 million SNPs in 103 domesticated and pre-domestication Zea mays varieties, as well as in a representative from the sister genus Tripsacum. See also: News and Views by Huang & Han Comparative population genomics of maize domestication and improvement   pp808 - 811 Matthew B Hufford, Xun Xu, Joost van Heerwaarden, Tanja Pyhäjärvi, Jer-Ming Chia, Reed A Cartwright, Robert J Elshire, Jeffrey C Glaubitz, Kate E Guill, Shawn M Kaeppler, Jinsheng Lai, Peter L Morrell, Laura M Shannon, Chi Song, Nathan M Springer, Ruth A Swanson-Wagner, Peter Tiffin, Jun Wang, Gengyun Zhang, John Doebley, Michael D McMullen, Doreen Ware, Edward S Buckler, Shuang Yang & Jeffrey Ross-Ibarra doi:10.1038/ng.2309 Jeff Ross-Ibarra and colleagues report a population genomic analysis of maize evolution. They analyze genome-wide evidence for selection during the initial domestication of wild maize and during the improvement of landraces to modern inbred breeds. Their findings suggest stronger selection during domestication compared to improvement. See also: News and Views by Huang & Han Genome-wide genetic changes during modern breeding of maize   pp812 - 815 Yinping Jiao, Hainan Zhao, Longhui Ren, Weibin Song, Biao Zeng, Jinjie Guo, Baobao Wang, Zhipeng Liu, Jing Chen, Wei Li, Mei Zhang, Shaojun Xie and Jinsheng Lai doi:10.1038/ng.2312 Jinsheng Lai and colleagues report the resequencing of 278 inbred maize lines and perform a genome-wide analysis of genetic changes during modern breeding. Using SNP imputation, the authors also perform a genome-wide association study for cob color, silk color and date to anthesis. The authors identified association signals with significant P values near known targets. See also: News and Views by Huang & Han The beet R locus encodes a new cytochrome P450 required for red betalain production   pp816 - 820 Gregory J Hatlestad, Rasika M Sunnadeniya, Neda A Akhavan, Antonio Gonzalez, Irwin L Goldman, J Mitchell McGrath and Alan M Lloyd doi:10.1038/ng.2297 Alan Lloyd and colleagues report the mapping of a gene encoding a novel cytochrome P450, CYP76AD1, to the classic R locus in beet that is responsible for red versus yellow pigment. Technical Reports Top Genome-wide efficient mixed-model analysis for association studies   pp821 - 824 Xiang Zhou and Matthew Stephens doi:10.1038/ng.2310 Matthew Stephens and Xiang Zhou report an efficient exact method for accounting for population stratification and relatedness in genome-wide association analyses. Their method, genome-wide efficient mixed-model association (GEMMA) is implemented in freely available software. An efficient multi-locus mixed-model approach for genome-wide association studies in structured populations   pp825 - 830 Vincent Segura, Bjarni J Vilhjálmsson, Alexander Platt, Arthur Korte, Ümit Seren, Quan Long & Magnus Nordborg doi:10.1038/ng.2314 Magnus Nordborg and colleagues report a multi-locus mixed-model method (MLMM) for genome-wide association studies in structured populations. Their simulations show that MLMM offers increased power and a reduced false discovery rate, and applications to both human and Arabidopsis thaliana data sets identify new associations and allelic heterogeneity. Corrigenda Top Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs   p831 S Hong Lee, Teresa R DeCandia, Stephan Ripke, Jian Yang, The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), The International Schizophrenia Consortium (ISC), The Molecular Genetics of Schizophrenia Collaboration (MGS), Patrick F Sullivan, Michael E Goddard, Matthew C Keller, Peter M Visscher & Naomi R Wray doi:10.1038/ng0712-831a Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells   p831 Matthias Stadtfeld, Effie Apostolou, Francesco Ferrari, Jiho Choi, Ryan M Walsh, Taiping Chen, Steen S K Ooi, Sang Yong Kim, Timothy H Bestor, Toshi Shioda, Peter J Park & Konrad Hochedlinger doi:10.1038/ng0712-831b A genome-wide association study identifies susceptibility loci for Wilms tumor   p831 Clare Turnbull, Elizabeth R Perdeaux, David Pernet, Arlene Naranjo, Anthony Renwick, Sheila Seal, Rosa Maria Munoz-Xicola, Sandra Hanks, Ingrid Slade, Anna Zachariou, Margaret Warren-Perry, Elise Ruark, Mary Gerrard, Juliet Hale, Martin Hewitt, Janice Kohler, Sheila Lane, Gill Levitt, Mabrook Madi, Bruce Morland, Veronica Neefjes, James Nicholdson, Susan Picton, Barry Pizer, Milind Ronghe, Michael Stevens, Heidi Traunecker, Charles A Stiller, Kathy Pritchard-Jones, Jeffrey Dome, Paulv Grundy & Nazneen Rahman doi:10.1038/ng0712-831c Top Advertisement Nature Genetics and the Wellcome Trust present: The Genomics of Common Diseases 2012 September 19-22, 2012 - Potomac, MD, USA For more information and to register, visit: www.nature.com/natureconferences/gcd2012 Abstract submission deadline- June 28, 2012   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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