Nature Genetics Contents: October 2016 pp 1101 - 1296

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Advertisement Before setting up a PCR run, the quality and quantity of the template DNA has to be determined. Depending on the concentration, different techniques are appropriate. Drop measurements for low volume, fluorescence methods for low concentration or UV/Vis detection for standard samples. The Eppendorf Detection portfolio offers the right solution for all kind of samples. Click here  TABLE OF CONTENTS October 2016 Volume 48, Issue 10 Editorial News and Views Analysis Articles Letters Technical Report Erratum Corrigenda Advertisement   10x Genomics Webinar   Dr. Rahul Satija from NYU Center for Genomics and Systems Biology presents data from a 68,000 cell dataset, exploring gene expression profiles from thousands of distinct, single cells per sample. Using Seurat, an R toolkit, he will explain how this visualization tool effectively subcategorizes very large cellular datasets that characterize single cell RNA-Seq. Join us on October 4th! Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Gene Editing: Bacterial Immunity to Global Impact Explore gene editing's potential across the biological spectrum, and how advances in human health, disease control & environmental engineering could change our perspective & place in the natural world. Join us @ MacLeod Auditorium, University of Toronto or watch live via webcast on Fri. October 28, 2016, 9:00-14:30 EST   Advertisement nature.com webcasts Springer Nature presents a custom webcast on Pure protein: optimal resin selection to maximize purification efficiency Date: Thursday September 29, 2016 Time: 8AM PDT, 11AM EDT, 4PM BST, 5PM CEST  Register at: An expert panel will answer all your questions regarding resin selection strategies following the webinar. Sponsored by: Thermo Fisher Scientific     Advertisement 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.   Editorial Top Legible ledgers   p1101 doi:10.1038/ng.3690 A prevalent but trivial systematic error in supplementary tables provides a reminder that genomic and other large data files are most usable when they are readable by both humans and machines. It is best practice to deposit large files in public databases and to provide accession links for peer review rather than to delay data deposition until publication. News and Views Top A saltationist theory of cancer evolution   pp1102 - 1103 Florian Markowetz doi:10.1038/ng.3687 A new study based on single-nucleus sequencing reports that triple-negative breast cancers acquire copy number aberrations in short punctuated bursts in the earliest stages of tumor evolution, rather than continuously and gradually, challenging prevailing models of tumor evolution. See also: Article by Gao et al. How the codfish changed its immune system   pp1103 - 1104 Peter Parham doi:10.1038/ng.3684 A common ancestor of the modern codfish acquired a set of mutations that eliminated a major arm of the adaptive immune system—the MHC II pathway of antigen presentation to CD4+ T cells. Subsequent to this event, there was a radiation of these fish in which the number and diversity of MHC I genes increased in species-specific ways. See also: Article by Malmstrom et al. Nucleosome mapping in plasma DNA predicts cancer gene expression   pp1105 - 1106 Muhammed Murtaza and Carlos Caldas doi:10.1038/ng.3686 A new study demonstrates that genomic sequencing coverage of plasma DNA fragments around transcription start sites reflects the expression levels of genes in corresponding tumors. This approach may enable noninvasive monitoring of treatment-induced changes in gene expression for patients with cancer. See also: Letter by Ulz et al. Genetics JOBS of the week Associate / Full Professor of Genetics University of Pennsylvania - Perelman School of Medicine Postdoctoral Position- Genetics Department Albert Einstein College of Medicine in New York Assistant Professor of Biology (Genetics) - Tenure Track Hamilton College Tenure-track Professor of Human Genetics at UCLA University of California, Los Angeles Post Doctoral Fellow / Genetics, Genomics & Informatics The University of Tennessee Health Science Center More Science jobs from Genetics EVENT Computational Molecular Evolution 8th - 19th May 2017 Cambridge, UK More science events from Analysis Top Patterns of genic intolerance of rare copy number variation in 59,898 human exomes   pp1107 - 1111 Douglas M Ruderfer, Tymor Hamamsy, Monkol Lek, Konrad J Karczewski, David Kavanagh et al. doi:10.1038/ng.3638 Douglas Ruderfer, Shaun Purcell and colleagues characterized the rates and properties of rare genic copy number variants in exome sequencing data from nearly 60,000 individuals in the Exome Aggregation Consortium. These data are available through an integrated database that spans the spectrum of human genetic variation, aiding in the interpretation of personal genomes and population-based disease studies. The rules and impact of nonsense-mediated mRNA decay in human cancers   pp1112 - 1118 Rik G H Lindeboom, Fran Supek and Ben Lehner doi:10.1038/ng.3664 Ben Lehner and colleagues analyze data from matched exomes and transcriptomes from tumors across 27 cancer types to elucidate rules linking premature termination codon location to nonsense-mediated mRNA decay (NMD). They propose a model that explains variability in NMD efficiency and find evidence of positive and negative selection on NMD-initiating mutations in tumors. Articles Top Punctuated copy number evolution and clonal stasis in triple-negative breast cancer   pp1119 - 1130 Ruli Gao, Alexander Davis, Thomas O McDonald, Emi Sei, Xiuqing Shi et al. doi:10.1038/ng.3641 Nicholas Navin and colleagues use highly multiplexed single-nucleus sequencing to investigate DNA copy number evolution in patients with triple-negative breast cancer. Their data suggest that most copy number alterations are acquired at the earliest stages of tumor evolution in short punctuated bursts, followed by stable clonal expansions that form the tumor mass. See also: News and Views by Markowetz Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance   pp1131 - 1141 Maria Secrier, Xiaodun Li, Nadeera de Silva, Matthew D Eldridge, Gianmarco Contino et al. doi:10.1038/ng.3659 Rebecca Fitzgerald and colleagues report the whole-genome sequences of 129 esophageal adenocarcinomas, showing frequent copy number alterations and prevalent mutations in receptor tyrosine kinases concomitant with mitogenic activation. They further characterize mutation signatures and find three distinct molecular subtypes with potential for application to clinical diagnosis and treatment. Modulation of long noncoding RNAs by risk SNPs underlying genetic predispositions to prostate cancer   pp1142 - 1150 Haiyang Guo, Musaddeque Ahmed, Fan Zhang, Cindy Q Yao, SiDe Li et al. doi:10.1038/ng.3637 Housheng Hansen He and colleagues perform an integrated analysis and identify 45 candidate long noncoding RNAs (lncRNAs) associated with prostate cancer risk. They further show that a prostate cancer risk allele in the 8q24 region results in upregulation of the lncRNA PCAT1, which promotes prostate cancer cell proliferation and tumor growth. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension   pp1151 - 1161 Praveen Surendran, Fotios Drenos, Robin Young, Helen Warren, James P Cook et al. doi:10.1038/ng.3654 Patricia Munroe, Joanna Howson and colleagues genotype ∼350,000 individuals and identify 30 new blood pressure- or hypertension-associated risk loci. Their analyses provide insights into the pathophysiology of hypertension and highlight new potential targets for clinical intervention. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci   pp1162 - 1170 Chunyu Liu, Aldi T Kraja, Jennifer A Smith, Jennifer A Brody, Nora Franceschini et al. doi:10.1038/ng.3660 Daniel Chasman, Daniel Levy, Christopher Newton-Cheh, Georg Ehret and colleagues perform an association meta-analysis for blood pressure in ∼330,000 individuals and identify 31 new risk loci, implicating biological pathways related to vascular function and cardiometabolic traits. Their findings highlight potential therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals   pp1171 - 1184 Georg B Ehret, Teresa Ferreira, Daniel I Chasman, Anne U Jackson, Ellen M Schmidt et al. doi:10.1038/ng.3667 Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts   pp1185 - 1192 Emma M Jenkinson, Mathieu P Rodero, Paul R Kasher, Carolina Uggenti, Anthony Oojageer et al. doi:10.1038/ng.3661 Yanick Crow and colleagues report that biallelic mutations in SNORD118, which encodes the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. The mutations affect U8 expression, processing and protein binding and suggest a role for this snoRNA in cerebral vascular homeostasis. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution   pp1193 - 1203 M Ryan Corces, Jason D Buenrostro, Beijing Wu, Peyton G Greenside, Steven M Chan et al. doi:10.1038/ng.3646 Howard Chang, Ravindra Majeti and colleagues define the chromatin accessibility and transcriptional landscapes in 13 human primary blood cell types and in acute myeloid leukemia cells. They identify potential regulators governing hematopoietic differentiation and genetic elements linked to regulatory evolution in cancer cells. Evolution of the immune system influences speciation rates in teleost fishes OPEN   pp1204 - 1210 Martin Malmstrøm, Michael Matschiner, Ole K Tørresen, Bastiaan Star, Lars G Snipen et al. doi:10.1038/ng.3645 Kjetill S. Jakobsen, Sissel Jentoft and colleagues assemble partial draft genomes and analyze sequences from 66 teleost fish species to determine major histocompatibility complex (MHC) class I and class II gene status. They find that MHC II is absent from the Gadiformes lineage, while MHC I gene expansions have occurred multiple times. See also: News and Views by Parham Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings   pp1211 - 1217 Nicholas A Feasey, James Hadfield, Karen H Keddy, Timothy J Dallman, Jan Jacobs et al. doi:10.1038/ng.3644 Nicholas Feasey and colleagues report whole-genome sequence analysis of 675 isolates of Salmonella enterica serovar Enteritidis from 45 countries. They find evidence for a global epidemic clade associated with enterocolitis and two novel clades restricted to distinct regions of Africa and associated with invasive disease. Subgenome parallel selection is associated with morphotype diversification and convergent crop domestication in Brassica rapa and Brassica oleracea   pp1218 - 1224 Feng Cheng, Rifei Sun, Xilin Hou, Hongkun Zheng, Fenglan Zhang et al. doi:10.1038/ng.3634 Xiaowu Wang, Jian Wu, Guusje Bonnema and colleagues report resequencing and subgenome selection analysis of 199 Brassica rapa and 119 Brassica oleracea accessions representing diverse morphotypes. They identify 4 subgenome loci with evidence of parallel selection among subgenomes and 15 subgenome loci with evidence of parallel selection between species. The genome sequence of allopolyploid Brassica juncea and analysis of differential homoeolog gene expression influencing selection OPEN   pp1225 - 1232 Jinghua Yang, Dongyuan Liu, Xiaowu Wang, Changmian Ji, Feng Cheng et al. doi:10.1038/ng.3657 Mingfang Zhang, Sally Mackenzie and colleagues report the genome sequence of allopolyploid Brassica juncea and through comparative analysis suggest that A-subgenome evolution contributes to differences in agricultural subvarieties. They find that differential homoeolog gene expression from the subgenomes helps to shape the selection that distinguishes vegetable- and oil-use Brassica. Genetic variation in ZmVPP1 contributes to drought tolerance in maize seedlings   pp1233 - 1241 Xianglan Wang, Hongwei Wang, Shengxue Liu, Ali Ferjani, Jiansheng Li et al. doi:10.1038/ng.3636 Feng Qin and colleagues perform a genome-wide association study for drought tolerance in maize seedlings and find 42 candidate genes. They characterize a promoter insertion in the ZmVPP1 gene containing MYB-binding sites, which enables the drought-inducible expression of ZmVPP1, leading to drought tolerance, a phenotype confirmed through transgenic experiments. Transcription factors mediate condensin recruitment and global chromosomal organization in fission yeast   pp1242 - 1252 Kyoung-Dong Kim, Hideki Tanizawa, Osamu Iwasaki and Ken-ichi Noma doi:10.1038/ng.3647 Ken-ichi Noma and colleagues use ChIA-PET to identify genome-wide associations mediated by condensin and cohesin in fission yeast. They find that cohesin and condensin generate small and larger chromatin domains, respectively, and that condensin, but not cohesin, connects cell cycle-regulated genes bound by mitotic transcription factors. Advertisement AGRICULTURAL GENOMICS 2016 — FROM VARIATION TO IMPROVED PRODUCTION  Hosting Organizations: Institute of Plant Physiology and Ecology, SIBS, CAS | Nature Genetics November 6-8, 2016  Crowne Plaza Shanghai|Xiayang Lake, China REGISTER NOW!    Letters Top Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas   pp1253 - 1259 Victoria E Clark, Akdes Serin Harmanci, Hanwen Bai, Mark W Youngblood, Tong Ihn Lee et al. doi:10.1038/ng.3651 Murat Gunel and colleagues identify recurrent mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II, in a subset of meningiomas. They find that POLR2A-mutant tumors can be distinguished on the basis of their super-enhancer and gene expression profiles, which show dysregulation of key meningeal identity genes. Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer   pp1260 - 1266 Swneke D Bailey, Kinjal Desai, Ken J Kron, Parisa Mazrooei, Nicholas A Sinnott-Armstrong et al. doi:10.1038/ng.3650 Mathieu Lupien and colleagues report an enrichment of somatic mutations at the ESR1 cis-regulatory region in 7% of ESR1-positive breast cancers. They find that the activity of the recurrently mutated ESR1 enhancer is also influenced by breast cancer risk-associated SNPs. G-quadruplex structures mark human regulatory chromatin   pp1267 - 1272 Robert Hänsel-Hertsch, Dario Beraldi, Stefanie V Lensing, Giovanni Marsico, Katherine Zyner et al. doi:10.1038/ng.3662 Shankar Balasubramanian and colleagues examine endogenous DNA G-quadruplex (G4) structures in the context of chromatin by using G4 antibody-based ChIP-seq. They find that G4 structures are enriched in nucleosome-depleted regions and the promoters and 5′ UTRs of highly transcribed genes, suggesting a relationship between chromatin state, transcriptional output and G4 status. Inferring expressed genes by whole-genome sequencing of plasma DNA   pp1273 - 1278 Peter Ulz, Gerhard G Thallinger, Martina Auer, Ricarda Graf, Karl Kashofer et al. doi:10.1038/ng.3648 Michael Speicher and colleagues analyze plasma DNA whole-genome sequencing data from healthy donors and patients with cancer to infer nucleosome positioning on the basis of read depth coverage patterns. They use this approach to accurately predict expression of cancer driver genes from circulating tumor DNA in regions with somatic copy number gains. See also: News and Views by Murtaza & Caldas A reference panel of 64,976 haplotypes for genotype imputation   pp1279 - 1283 Shane McCarthy, Sayantan Das, Warren Kretzschmar, Olivier Delaneau, Andrew R Wood et al. doi:10.1038/ng.3643 Jonathan Marchini, Goncalo Abecasis, Richard Durbin and colleagues describe the construction of a reference panel of human haplotypes from whole-genome sequencing data. They are able to use this to accurately impute genotypes at low minor allele frequency and present remote server resources for use by the community. Next-generation genotype imputation service and methods   pp1284 - 1287 Sayantan Das, Lukas Forer, Sebastian Schönherr, Carlo Sidore, Adam E Locke et al. doi:10.1038/ng.3656 Christian Fuchsberger, Goncalo Abecasis and colleagues describe a new web-based imputation service that enables rapid imputation of large numbers of samples and allows convenient access to large reference panels of sequenced individuals. Their state space reduction provides a computationally efficient solution for genotype imputation with no loss in imputation accuracy. Technical Report Top Unsupervised detection of cancer driver mutations with parsimony-guided learning   pp1288 - 1294 Runjun D Kumar, S Joshua Swamidass and Ron Bose doi:10.1038/ng.3658 Runjun Kumar, S. Joshua Swamidass and Ron Bose present an unsupervised parsimony-guided method, ParsSNP, for prioritizing candidate cancer driver mutations. They apply ParsSNP to a gastric cancer data set and predict potential driver mutations not detected by other methods, including truncations in known tumor-suppressor genes and previously confirmed drivers. Corrigenda Top Corrigendum: Parallel evolution of male germline epigenetic poising and somatic development in animals   p1296 Bluma J Lesch, Sherman J Silber, John R McCarrey and David C Page doi:10.1038/ng1016-1296b Corrigendum: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine   p1296 Padhraig Gormley, Verneri Anttila, Bendik S Winsvold, Priit Palta, Tonu Esko et al. doi:10.1038/ng1016-1296c Corrigendum: Stromal contribution to the colorectal cancer transcriptome   p1296 Claudio Isella, Andrea Terrasi, Sara Erika Bellomo, Consalvo Petti, Giovanni Galatola et al. doi:10.1038/ng1016-1296d Erratum Top Erratum: Detection and interpretation of shared genetic influences on 42 human traits   p1296 Joseph K Pickrell, Tomaz Berisa, Jimmy Z Liu, Laure Segurel, Joyce Y Tung et al. doi:10.1038/ng1016-1296a Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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