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Nature Genetics

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https://www.readbyqxmd.com/read/29736016/resequencing-a-core-collection-of-upland-cotton-identifies-genomic-variation-and-loci-influencing-fiber-quality-and-yield
#1
Zhiying Ma, Shoupu He, Xingfen Wang, Junling Sun, Yan Zhang, Guiyin Zhang, Liqiang Wu, Zhikun Li, Zhihao Liu, Gaofei Sun, Yuanyuan Yan, Yinhua Jia, Jun Yang, Zhaoe Pan, Qishen Gu, Xueyuan Li, Zhengwen Sun, Panhong Dai, Zhengwen Liu, Wenfang Gong, Jinhua Wu, Mi Wang, Hengwei Liu, Keyun Feng, Huifeng Ke, Junduo Wang, Hongyu Lan, Guoning Wang, Jun Peng, Nan Wang, Liru Wang, Baoyin Pang, Zhen Peng, Ruiqiang Li, Shilin Tian, Xiongming Du
Upland cotton is the most important natural-fiber crop. The genomic variation of diverse germplasms and alleles underpinning fiber quality and yield should be extensively explored. Here, we resequenced a core collection comprising 419 accessions with 6.55-fold coverage depth and identified approximately 3.66 million SNPs for evaluating the genomic variation. We performed phenotyping across 12 environments and conducted genome-wide association study of 13 fiber-related traits. 7,383 unique SNPs were significantly associated with these traits and were located within or near 4,820 genes; more associated loci were detected for fiber quality than fiber yield, and more fiber genes were detected in the D than the A subgenome...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29736015/locus-specific-control-of-the-de-novo-dna-methylation-pathway-in-arabidopsis-by-the-classy-family
#2
Ming Zhou, Ana Marie S Palanca, Julie A Law
DNA methylation is essential for gene regulation, transposon silencing and imprinting. Although the generation of specific DNA methylation patterns is critical for these processes, how methylation is regulated at individual loci remains unclear. Here we show that a family of four putative chromatin remodeling factors, CLASSY (CLSY) 1-4, are required for both locus-specific and global regulation of DNA methylation in Arabidopsis thaliana. Mechanistically, these factors act in connection with RNA polymerase-IV (Pol-IV) to control the production of 24-nucleotide small interfering RNAs (24nt-siRNAs), which guide DNA methylation...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29736014/resequencing-of-243-diploid-cotton-accessions-based-on-an-updated-a-genome-identifies-the-genetic-basis-of-key-agronomic-traits
#3
Xiongming Du, Gai Huang, Shoupu He, Zhaoen Yang, Gaofei Sun, Xiongfeng Ma, Nan Li, Xueyan Zhang, Junling Sun, Min Liu, Yinhua Jia, Zhaoe Pan, Wenfang Gong, Zhaohui Liu, Heqin Zhu, Lei Ma, Fuyan Liu, Daigang Yang, Fan Wang, Wei Fan, Qian Gong, Zhen Peng, Liru Wang, Xiaoyang Wang, Shuangjiao Xu, Haihong Shang, Cairui Lu, Hongkun Zheng, Sanwen Huang, Tao Lin, Yuxian Zhu, Fuguang Li
The ancestors of Gossypium arboreum and Gossypium herbaceum provided the A subgenome for the modern cultivated allotetraploid cotton. Here, we upgraded the G. arboreum genome assembly by integrating different technologies. We resequenced 243 G. arboreum and G. herbaceum accessions to generate a map of genome variations and found that they are equally diverged from Gossypium raimondii. Independent analysis suggested that Chinese G. arboreum originated in South China and was subsequently introduced to the Yangtze and Yellow River regions...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29736013/utx-mediated-enhancer-and-chromatin-remodeling-suppresses-myeloid-leukemogenesis-through-noncatalytic-inverse-regulation-of-ets-and-gata-programs
#4
Malgorzata Gozdecka, Eshwar Meduri, Milena Mazan, Konstantinos Tzelepis, Monika Dudek, Andrew J Knights, Mercedes Pardo, Lu Yu, Jyoti S Choudhary, Emmanouil Metzakopian, Vivek Iyer, Haiyang Yun, Naomi Park, Ignacio Varela, Ruben Bautista, Grace Collord, Oliver Dovey, Dimitrios A Garyfallos, Etienne De Braekeleer, Saki Kondo, Jonathan Cooper, Berthold Göttgens, Lars Bullinger, Paul A Northcott, David Adams, George S Vassiliou, Brian J P Huntly
The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29713014/the-rosa-genome-provides-new-insights-into-the-domestication-of-modern-roses
#5
Olivier Raymond, Jérôme Gouzy, Jérémy Just, Hélène Badouin, Marion Verdenaud, Arnaud Lemainque, Philippe Vergne, Sandrine Moja, Nathalie Choisne, Caroline Pont, Sébastien Carrère, Jean-Claude Caissard, Arnaud Couloux, Ludovic Cottret, Jean-Marc Aury, Judit Szécsi, David Latrasse, Mohammed-Amin Madoui, Léa François, Xiaopeng Fu, Shu-Hua Yang, Annick Dubois, Florence Piola, Antoine Larrieu, Magali Perez, Karine Labadie, Lauriane Perrier, Benjamin Govetto, Yoan Labrousse, Priscilla Villand, Claudia Bardoux, Véronique Boltz, Céline Lopez-Roques, Pascal Heitzler, Teva Vernoux, Michiel Vandenbussche, Hadi Quesneville, Adnane Boualem, Abdelhafid Bendahmane, Chang Liu, Manuel Le Bris, Jérôme Salse, Sylvie Baudino, Moussa Benhamed, Patrick Wincker, Mohammed Bendahmane
Roses have high cultural and economic importance as ornamental plants and in the perfume industry. We report the rose whole-genome sequencing and assembly and resequencing of major genotypes that contributed to rose domestication. We generated a homozygous genotype from a heterozygous diploid modern rose progenitor, Rosa chinensis 'Old Blush'. Using single-molecule real-time sequencing and a meta-assembly approach, we obtained one of the most comprehensive plant genomes to date. Diversity analyses highlighted the mosaic origin of 'La France', one of the first hybrids combining the growth vigor of European species and the recurrent blooming of Chinese species...
April 30, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700475/genome-wide-association-analyses-identify-44-risk-variants-and-refine-the-genetic-architecture-of-major-depression
#6
Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till M F Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan F T Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas R H Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan I R Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Cheynna A Crowley, Hassan S Dashti, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Nicholas Eriksson, Valentina Escott-Price, Farnush Hassan Farhadi Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Paola Giusti-Rodríguez, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Eilis Hannon, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Ming Hu, Craig L Hyde, Marcus Ising, Rick Jansen, Fulai Jin, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Jacqueline M Lane, Yihan Li, Yun Li, Penelope A Lind, Xiaoxiao Liu, Leina Lu, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Jonathan Mill, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Shaun M Purcell, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Richa Saxena, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant B C Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Craig A Stockmeier, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Chao Tian, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E C J de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, David A Hinds, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela F A Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Ashley R Winslow, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700474/comparison-of-methods-that-use-whole-genome-data-to-estimate-the-heritability-and-genetic-architecture-of-complex-traits
#7
Luke M Evans, Rasool Tahmasbi, Scott I Vrieze, Gonçalo R Abecasis, Sayantan Das, Steven Gazal, Douglas W Bjelland, Teresa R de Candia, Michael E Goddard, Benjamin M Neale, Jian Yang, Peter M Visscher, Matthew C Keller
Multiple methods have been developed to estimate narrow-sense heritability, h2 , using single nucleotide polymorphisms (SNPs) in unrelated individuals. However, a comprehensive evaluation of these methods has not yet been performed, leading to confusion and discrepancy in the literature. We present the most thorough and realistic comparison of these methods to date. We used thousands of real whole-genome sequences to simulate phenotypes under varying genetic architectures and confounding variables, and we used array, imputed, or whole genome sequence SNPs to obtain 'SNP-heritability' estimates...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700473/an-analytical-framework-for-whole-genome-sequence-association-studies-and-its-implications-for-autism-spectrum-disorder
#8
Donna M Werling, Harrison Brand, Joon-Yong An, Matthew R Stone, Lingxue Zhu, Joseph T Glessner, Ryan L Collins, Shan Dong, Ryan M Layer, Eirene Markenscoff-Papadimitriou, Andrew Farrell, Grace B Schwartz, Harold Z Wang, Benjamin B Currall, Xuefang Zhao, Jeanselle Dea, Clif Duhn, Carolyn A Erdman, Michael C Gilson, Rachita Yadav, Robert E Handsaker, Seva Kashin, Lambertus Klei, Jeffrey D Mandell, Tomasz J Nowakowski, Yuwen Liu, Sirisha Pochareddy, Louw Smith, Michael F Walker, Matthew J Waterman, Xin He, Arnold R Kriegstein, John L Rubenstein, Nenad Sestan, Steven A McCarroll, Benjamin M Neale, Hilary Coon, A Jeremy Willsey, Joseph D Buxbaum, Mark J Daly, Matthew W State, Aaron R Quinlan, Gabor T Marth, Kathryn Roeder, Bernie Devlin, Michael E Talkowski, Stephan J Sanders
Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700472/inferring-parsimonious-migration-histories-for-metastatic-cancers
#9
Mohammed El-Kebir, Gryte Satas, Benjamin J Raphael
Metastasis is the migration of cancerous cells from a primary tumor to other anatomical sites. Although metastasis was long thought to result from monoclonal seeding, or single cellular migrations, recent phylogenetic analyses of metastatic cancers have reported complex patterns of cellular migrations between sites, including polyclonal migrations and reseeding. However, accurate determination of migration patterns from somatic mutation data is complicated by intratumor heterogeneity and discordance between clonal lineage and cellular migration...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700471/telobox-motifs-recruit-clf-swn-prc2-for-h3k27me3-deposition-via-trb-factors-in-arabidopsis
#10
Yue Zhou, Yuejun Wang, Kristin Krause, Tingting Yang, Joram A Dongus, Yijing Zhang, Franziska Turck
Polycomb repressive complexes (PRCs) control organismic development in higher eukaryotes through epigenetic gene repression1-4 . PRC proteins do not contain DNA-binding domains, thus prompting questions regarding how PRCs find their target loci 5 . Here we present genome-wide evidence of PRC2 recruitment by telomere-repeat-binding factors (TRBs) through telobox-related motifs in Arabidopsis. A triple trb1-2, trb2-1, and trb3-2 (trb1/2/3) mutant with a developmental phenotype and a transcriptome strikingly similar to those of strong PRC2 mutants showed redistribution of trimethyl histone H3 Lys27 (H3K27me3) marks and lower H3K27me3 levels, which were correlated with derepression of TRB1-target genes...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700470/no-evidence-for-unknown-archaic-ancestry-in-south-asia
#11
LETTER
Pontus Skoglund, Swapan Mallick, Nick Patterson, David Reich
No abstract text is available yet for this article.
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700469/expanding-the-toolbox-for-3d-genomics
#12
Ralph Stadhouders
No abstract text is available yet for this article.
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700468/sizing-up-whole-genome-sequencing-studies-of-common-diseases
#13
Naomi R Wray, Jacob Gratten
No abstract text is available yet for this article.
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700467/digestion-ligation-only-hi-c-is-an-efficient-and-cost-effective-method-for-chromosome-conformation-capture
#14
Da Lin, Ping Hong, Siheng Zhang, Weize Xu, Muhammad Jamal, Keji Yan, Yingying Lei, Liang Li, Yijun Ruan, Zhen F Fu, Guoliang Li, Gang Cao
Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29700466/straws-in-a-haystack
#15
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29686387/detection-of-widespread-horizontal-pleiotropy-in-causal-relationships-inferred-from-mendelian-randomization-between-complex-traits-and-diseases
#16
Marie Verbanck, Chia-Yen Chen, Benjamin Neale, Ron Do
Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the 'no horizontal pleiotropy' assumption can cause severe bias in MR. We developed the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that the MR-PRESSO test is best suited when horizontal pleiotropy occurs in <50% of instruments...
April 23, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29674745/publisher-correction-the-sea-lamprey-germline-genome-provides-insights-into-programmed-genome-rearrangement-and-vertebrate-evolution
#17
Jeramiah J Smith, Nataliya Timoshevskaya, Chengxi Ye, Carson Holt, Melissa C Keinath, Hugo J Parker, Malcolm E Cook, Jon E Hess, Shawn R Narum, Francesco Lamanna, Henrik Kaessmann, Vladimir A Timoshevskiy, Courtney K M Waterbury, Cody Saraceno, Leanne M Wiedemann, Sofia M C Robb, Carl Baker, Evan E Eichler, Dorit Hockman, Tatjana Sauka-Spengler, Mark Yandell, Robb Krumlauf, Greg Elgar, Chris T Amemiya
In the version of this article initially published, the present addresses for authors Dorit Hockman and Chris Amemiya were switched. The error has been corrected in the HTML and PDF versions of the article.
April 19, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29674744/author-correction-genome-wide-analysis-of-multi-and-extensively-drug-resistant-mycobacterium-tuberculosis
#18
Francesc Coll, Jody Phelan, Grant A Hill-Cawthorne, Mridul B Nair, Kim Mallard, Shahjahan Ali, Abdallah M Abdallah, Saad Alghamdi, Mona Alsomali, Abdallah O Ahmed, Stephanie Portelli, Yaa Oppong, Adriana Alves, Theolis Barbosa Bessa, Susana Campino, Maxine Caws, Anirvan Chatterjee, Amelia C Crampin, Keertan Dheda, Nicholas Furnham, Judith R Glynn, Louis Grandjean, Dang Minh Ha, Rumina Hasan, Zahra Hasan, Martin L Hibberd, Moses Joloba, Edward C Jones-López, Tomoshige Matsumoto, Anabela Miranda, David J Moore, Nora Mocillo, Stefan Panaiotov, Julian Parkhill, Carlos Penha, João Perdigão, Isabel Portugal, Zineb Rchiad, Jaime Robledo, Patricia Sheen, Nashwa Talaat Shesha, Frik A Sirgel, Christophe Sola, Erivelton Oliveira Sousa, Elizabeth M Streicher, Paul Van Helden, Miguel Viveiros, Robert M Warren, Ruth McNerney, Arnab Pain, Taane G Clark
In the version of this article initially published, the URL listed for TubercuList was incorrect. The correct URL is https://mycobrowser.epfl.ch/. The error has been corrected in the HTML and PDF versions of the article.
April 19, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29662168/genome-wide-association-meta-analysis-of-individuals-of-european-ancestry-identifies-new-loci-explaining-a-substantial-fraction-of-hair-color-variation-and-heritability
#19
Pirro G Hysi, Ana M Valdes, Fan Liu, Nicholas A Furlotte, David M Evans, Veronique Bataille, Alessia Visconti, Gibran Hemani, George McMahon, Susan M Ring, George Davey Smith, David L Duffy, Gu Zhu, Scott D Gordon, Sarah E Medland, Bochao D Lin, Gonneke Willemsen, Jouke Jan Hottenga, Dragana Vuckovic, Giorgia Girotto, Ilaria Gandin, Cinzia Sala, Maria Pina Concas, Marco Brumat, Paolo Gasparini, Daniela Toniolo, Massimiliano Cocca, Antonietta Robino, Seyhan Yazar, Alex W Hewitt, Yan Chen, Changqing Zeng, Andre G Uitterlinden, M Arfan Ikram, Merel A Hamer, Cornelia M van Duijn, Tamar Nijsten, David A Mackey, Mario Falchi, Dorret I Boomsma, Nicholas G Martin, David A Hinds, Manfred Kayser, Timothy D Spector
Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29662167/sequencing-of-prostate-cancers-identifies-new-cancer-genes-routes-of-progression-and-drug-targets
#20
David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
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