Nature Genetics Contents: April 2016 pp 343 - 473

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Advertisement Eppendorf's product portfolio offers flexible solutions for preparing, handling, and analyzing samples and cells. Special accessories and smart innovations, e.g. for centrifugation of spin columns or photometric quantification in the micro volume range, further lighten the daily work in the lab. See how Eppendorf products fit to your workflow: www.eppendorf.com/workflows TABLE OF CONTENTS April 2016 Volume 48, Issue 4 Editorial News and Views Analysis Brief Communication Articles Letter Technical Report Errata Corrigenda Advertisement   QScience.com Highlights is a regularly updated online platform which highlights the best of published research, handpicked by Nature Journals' editors, from QScience.com. Stay up-to-date with the latest research and reviews  qscience.nature.com Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement nature.com webcasts Nature Publishing Group presents a custom webcast on: Analyzing immune cell communities on a massive scale with single-cell RNA-Seq Speaker: Cole Trapnell, Assistant Professor, University of Washington Thursday April 21, 2016 11AM PDT, 2PM EDT Register for the webcast and live Q&A session Sponsored by: 10x Genomics     Advertisement Human Genome Variation (HGV) is an online, open access journal dedicated to sharing output of the studies to explore variation and mutation in the human genome in different format. Read the latest featured article on the genomic architecture of inflammatory bowel disease.    Editorial Top FAIR principles for data stewardship   p343 doi:10.1038/ng.3544 The FAIR data principles are simple guidelines for ensuring that machines can find and use data, supporting data reuse by individuals. More—and better—research can be generated by designing data and algorithms to be findable, accessible, interoperable and reusable, together with the tools and workflows that led to these data. News and Views Top The gar is a fish... is a bird... is a mammal?   pp344 - 345 David M Parichy doi:10.1038/ng.3532 Teleosts have emerged as important model organisms, yet their ancestrally duplicated genomes sometimes complicate developmental genetic analyses and comparisons to humans. A new genome sequence of spotted gar, a fish related to teleosts but lacking a duplicated genome, now helps to bridge human and teleost biology. See also: Article by Braasch et al. Tet proteins enhance the developmental hourglass   pp345 - 347 Peter G Hendrickson and Bradley R Cairns doi:10.1038/ng.3533 A new study compares DNA methylation profiles in developing zebrafish, Xenopus tropicalis and mice and suggests roles for Tet proteins in demethylating conserved gene enhancers during the phylotypic period of early development. These findings provide an epigenetic underpinning for the 'hourglass' model. See also: Article by Bogdanović et al. Recurrent mutation at the classical haptoglobin structural polymorphism   pp347 - 348 Edward J Hollox and Louise V Wain doi:10.1038/ng.3534 Polymorphism of haptoglobin in human serum was first discovered over 60 years ago. A new paper characterizes the complex structural variation at the HP locus in detail and, by using imputation from flanking SNP genotype data, shows that it affects blood cholesterol levels. See also: Article by Boettger et al. Genetics JOBS of the week Tenure-Track / Tenured Faculty Position, Translational and Clinical Pharmacology Washington University in St. Louis Postdoctoral Fellowship in Biomedical Science (Cancer Research) Institute for Cancer Genetics Columbia University Medical Center Junior Group Leader in the systems biology programme CRG – Centre for Genomic Regulation Postdoctoral Fellow The University of Tennessee Health Science Center Postdoctoral Research Associate University of Illinois Chicago College of Medicine More Science jobs from Genetics EVENT Drosophila Genetics and Genomics 3rd July - 10th July 2016 Hinxton, UK More science events from Analysis Top An expanded sequence context model broadly explains variability in polymorphism levels across the human genome   pp349 - 355 Varun Aggarwala and Benjamin F Voight doi:10.1038/ng.3511 Varun Aggarwala and Benjamin Voight analyze human polymorphism data and develop an expanded sequence context model that explains >81% of variability in substitution probabilities, highlighting mutation-promoting motifs. Using their model, they present substitution intolerance scores for genes and a new intolerance score for amino acids, and demonstrate clinical use of the model in neuropsychiatric diseases. Brief Communication Top Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer   pp356 - 358 Hikmat A Al-Ahmadie, Gopa Iyer, Byron H Lee, Sasinya N Scott, Rohit Mehra et al. doi:10.1038/ng.3503 David Solit and colleagues report that inactivating CDH1 mutations are found in 84% of plasmacytoid bladder cancer samples tested and are not found in other bladder cancer subtypes. CRISPR/Cas9-mediated knockout of CDH1 in cell lines leads to enhanced cellular migration. Articles Top Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels   pp359 - 366 Linda M Boettger, Rany M Salem, Robert E Handsaker, Gina M Peloso, Sekar Kathiresan et al. doi:10.1038/ng.3510 Steven McCarroll and colleagues present a detailed study of copy number variation of exons within the human HP (haptoglobin) gene. They show that HP exons undergo recurring deletions that, together with local SNP variation, influence LDL and total cholesterol levels in human populations. See also: News and Views by Hollox & Wain NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity   pp367 - 373 Takaya Moriyama, Rina Nishii, Virginia Perez-Andreu, Wenjian Yang, Federico Antillon Klussmann et al. doi:10.1038/ng.3508 Jun Yang and colleagues perform targeted sequencing of NUDT15 and identify loss-of-function variants associated with thiopurine intolerance. Functionally, they show that NUDT15 inactivates thiopurine metabolites, providing a mechanism to explain the association between NUDT15 loss-of-function variants and thiopurine toxicity. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170   pp374 - 386 Alison M Dunning, Kyriaki Michailidou, Karoline B Kuchenbaecker, Deborah Thompson, Juliet D French et al. doi:10.1038/ng.3521 Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer-related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170. Gene regulatory mechanisms underpinning prostate cancer susceptibility   pp387 - 397 Thomas Whitington, Ping Gao, Wei Song, Helen Ross-Adams, Alastair D Lamb et al. doi:10.1038/ng.3523 Thomas Whitington and colleagues present a detailed characterization of gene regulatory mechanisms underlying prostate cancer susceptibility. Their analysis highlights key mechanisms altered by disease-associated SNPs, including widespread disruption of ternary complexes involving AR, FOXA1 and HOXB13. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma   pp398 - 406 Ximena Bonilla, Laurent Parmentier, Bryan King, Fedor Bezrukov, Gürkan Kaya et al. doi:10.1038/ng.3525 Sergey Nikolaev, Stylianos Antonarakis and colleagues analyze the genetic architecture of 293 basal cell carcinomas (BCCs) and characterize their mutational landscape. They observe UV signature mutations and identify new driver mutations in MYCN, PTPN14 and LATS1 in BCC. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations   pp407 - 416 Raphael Bueno, Eric W Stawiski, Leonard D Goldstein, Steffen Durinck, Assunta De Rienzo et al. doi:10.1038/ng.3520 Raphael Bueno, Eric Stawiski, Somasekar Seshagiri and colleagues present a comprehensive genomic analysis of malignant pleural mesothelioma. They identify four distinct molecular subtypes using RNA-seq data and highlight recurrent somatic mutations, gene fusions and splicing alterations. Active DNA demethylation at enhancers during the vertebrate phylotypic period   pp417 - 426 Ozren Bogdanović, Arne H Smits, Elisa de la Calle Mustienes, Juan J Tena, Ethan Ford et al. doi:10.1038/ng.3522 Ozren Bogdanović, Ryan Lister, José Luis Gómez-Skarmeta, Michiel Vermeulen and colleagues report widespread DNA demethylation at developmental enhancers during the phylotypic period in zebrafish, Xenopus and mouse embryos. Their findings suggest a conserved role for Tet proteins and active DNA demethylation in the regulation of phylotypic enhancers. See also: News and Views by Hendrickson & Cairns The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons OPEN   pp427 - 437 Ingo Braasch, Andrew R Gehrke, Jeramiah J Smith, Kazuhiko Kawasaki, Tereza Manousaki et al. doi:10.1038/ng.3526 Ingo Braasch, John Postlethwait and colleagues report the genome of the spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before genome duplication. Their data provide insights into the evolution of genes involved in immunity, mineralization and development and facilitate the comparison of cis-regulatory elements between teleosts and humans. See also: News and Views by Parichy The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut OPEN   pp438 - 446 David John Bertioli, Steven B Cannon, Lutz Froenicke, Guodong Huang, Andrew D Farmer et al. doi:10.1038/ng.3517 David Bertioli and colleagues report the genomes of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut, Arachis hypogaea. Their analyses are a first step in understanding the evolution of the peanut's tetraploid genome. OsSPL13 controls grain size in cultivated rice   pp447 - 456 Lizhen Si, Jiaying Chen, Xuehui Huang, Hao Gong, Jianghong Luo et al. doi:10.1038/ng.3518 Bin Han and colleagues present a genome-wide association analysis of grain size and shape in cultivated rice and identify a major locus for grain size encoding the transcription factor OsSPL13. They find that the large-grain allele in tropical japonica cultivars was introgressed from indica varieties during selection for improved grain yield. Letter Top Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome   pp457 - 465 Daniela A Braun, Carolin E Sadowski, Stefan Kohl, Svjetlana Lovric, Susanne A Astrinidis et al. doi:10.1038/ng.3512 Friedhelm Hildebrandt and colleagues identify mutations in NUP93, NUP205 or XPO5 in patients with steroid-resistant nephrotic syndrome. They show that NUP93 and XPO5 interact with SMAD4 and that NUP93 mutations interfere with BMP7-SMAD4 signaling in podocytes. Technical Report Top A multiple-phenotype imputation method for genetic studies   pp466 - 472 Andrew Dahl, Valentina Iotchkova, Amelie Baud, Åsa Johansson, Ulf Gyllensten et al. doi:10.1038/ng.3513 Andy Dahl and colleagues present a method for imputing missing phenotype data in genetic studies with multiple correlated phenotypes where samples can have any level of relatedness. They apply their method to simulated and real data sets and show that it improves the sensitivity to detect association signals. Corrigenda Top Corrigendum: Germline RECQL mutations are associated with breast cancer susceptibility   p473 Cezary Cybulski, Jian Carrot-Zhang, Wojciech Kluźniak, Barbara Rivera, Aniruddh Kashyap et al. doi:10.1038/ng0329-473c Corrigendum: Mutations in the transcriptional repressor REST predispose to Wilms tumor   p473 Shazia S Mahamdallie, Sandra Hanks, Kristen L Karlin, Anna Zachariou, Elizabeth R Perdeaux et al. doi:10.1038/ng0329-473d Corrigendum: Fine-mapping cellular QTLs with RASQUAL and ATAC-seq   p473 Natsuhiko Kumasaka, Andrew J Knights and Daniel J Gaffney doi:10.1038/ng0329-473e Errata Top Erratum: NRF2 regulates serine biosynthesis in non-small cell lung cancer   p473 Gina M DeNicola, Pei-Hsuan Chen, Edouard Mullarky, Jessica A Sudderth, Zeping Hu et al. doi:10.1038/ng0329-473a Erratum: Multisystem Lewy body disease and the other parkinsonian disorders   p473 J William Langston, Birgitt Schüle, Linda Rees, R Jeremy Nichols and Carrolee Barlow doi:10.1038/ng0329-473b 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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