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Institution

Broad Institute

NonprofitCambridge, Massachusetts, United States
About: Broad Institute is a nonprofit organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 6584 authors who have published 11618 publications receiving 1522743 citations. The organization is also known as: Eli and Edythe L. Broad Institute of MIT and Harvard.


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Journal ArticleDOI
TL;DR: A genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 that encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells is reported.
Abstract: Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).

1,342 citations

Journal ArticleDOI
Brian J. Haas1, Sophien Kamoun2, Sophien Kamoun3, Michael C. Zody1, Michael C. Zody4, Rays H. Y. Jiang5, Rays H. Y. Jiang1, Robert E. Handsaker1, Liliana M. Cano2, Manfred Grabherr1, Chinnappa D. Kodira6, Chinnappa D. Kodira1, Sylvain Raffaele2, Trudy Torto-Alalibo3, Trudy Torto-Alalibo6, Tolga O. Bozkurt2, Audrey M. V. Ah-Fong7, Lucia Alvarado1, Vicky L. Anderson8, Miles R. Armstrong9, Anna O. Avrova9, Laura Baxter10, Jim Beynon10, Petra C. Boevink9, Stephanie R. Bollmann11, Jorunn I. B. Bos3, Vincent Bulone12, Guohong Cai13, Cahid Cakir3, James C. Carrington14, Megan Chawner15, Lucio Conti16, Stefano Costanzo11, Richard Ewan16, Noah Fahlgren14, Michael A. Fischbach17, Johanna Fugelstad12, Eleanor M. Gilroy9, Sante Gnerre1, Pamela J. Green18, Laura J. Grenville-Briggs8, John Griffith15, Niklaus J. Grünwald11, Karolyn Horn15, Neil R. Horner8, Chia-Hui Hu19, Edgar Huitema3, Dong-Hoon Jeong18, Alexandra M. E. Jones2, Jonathan D. G. Jones2, Richard W. Jones11, Elinor K. Karlsson1, Sridhara G. Kunjeti20, Kurt Lamour21, Zhenyu Liu3, Li-Jun Ma1, Dan MacLean2, Marcus C. Chibucos22, Hayes McDonald23, Jessica McWalters15, Harold J. G. Meijer5, William Morgan24, Paul Morris25, Carol A. Munro8, Keith O'Neill1, Keith O'Neill6, Manuel D. Ospina-Giraldo15, Andrés Pinzón, Leighton Pritchard9, Bernard H Ramsahoye26, Qinghu Ren27, Silvia Restrepo, Sourav Roy7, Ari Sadanandom16, Alon Savidor28, Sebastian Schornack2, David C. Schwartz29, Ulrike Schumann8, Ben Schwessinger2, Lauren Seyer15, Ted Sharpe1, Cristina Silvar2, Jing Song3, David J. Studholme2, Sean M. Sykes1, Marco Thines2, Marco Thines30, Peter J. I. van de Vondervoort5, Vipaporn Phuntumart25, Stephan Wawra8, R. Weide5, Joe Win2, Carolyn A. Young3, Shiguo Zhou29, William E. Fry13, Blake C. Meyers18, Pieter van West8, Jean B. Ristaino19, Francine Govers5, Paul R. J. Birch31, Stephen C. Whisson9, Howard S. Judelson7, Chad Nusbaum1 
17 Sep 2009-Nature
TL;DR: The sequence of the P. infestans genome is reported, which at ∼240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates and probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
Abstract: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

1,341 citations

Journal ArticleDOI
Feng Yue1, Feng Yue2, Yong Cheng3, Alessandra Breschi, Jeff Vierstra4, Weisheng Wu5, Weisheng Wu1, Tyrone Ryba6, Tyrone Ryba7, Richard Sandstrom4, Zhihai Ma3, Carrie A. Davis8, Benjamin D. Pope6, Yin Shen2, Dmitri D. Pervouchine, Sarah Djebali, Robert E. Thurman4, Rajinder Kaul4, Eric Rynes4, Anthony Kirilusha9, Georgi K. Marinov9, Brian A. Williams9, Diane Trout9, Henry Amrhein9, Katherine I. Fisher-Aylor9, Igor Antoshechkin9, Gilberto DeSalvo9, Lei Hoon See8, Meagan Fastuca8, Jorg Drenkow8, Chris Zaleski8, Alexander Dobin8, Pablo Prieto, Julien Lagarde, Giovanni Bussotti, Andrea Tanzer10, Olgert Denas11, Kanwei Li11, M. A. Bender12, M. A. Bender4, Miaohua Zhang12, Rachel Byron12, Mark Groudine4, Mark Groudine12, David McCleary2, Long Pham2, Zhen Ye2, Samantha Kuan2, Lee Edsall2, Yi-Chieh Wu13, Matthew D. Rasmussen13, Mukul S. Bansal13, Manolis Kellis13, Manolis Kellis14, Cheryl A. Keller1, Christapher S. Morrissey1, Tejaswini Mishra1, Deepti Jain1, Nergiz Dogan1, Robert S. Harris1, Philip Cayting3, Trupti Kawli3, Alan P. Boyle5, Alan P. Boyle3, Ghia Euskirchen3, Anshul Kundaje3, Shin Lin3, Yiing Lin3, Camden Jansen15, Venkat S. Malladi3, Melissa S. Cline16, Drew T. Erickson3, Vanessa M. Kirkup16, Katrina Learned16, Cricket A. Sloan3, Kate R. Rosenbloom16, Beatriz Lacerda de Sousa17, Kathryn Beal, Miguel Pignatelli, Paul Flicek, Jin Lian18, Tamer Kahveci19, Dongwon Lee20, W. James Kent16, Miguel Santos17, Javier Herrero21, Cedric Notredame, Audra K. Johnson4, Shinny Vong4, Kristen Lee4, Daniel Bates4, Fidencio Neri4, Morgan Diegel4, Theresa K. Canfield4, Peter J. Sabo4, Matthew S. Wilken4, Thomas A. Reh4, Erika Giste4, Anthony Shafer4, Tanya Kutyavin4, Eric Haugen4, Douglas Dunn4, Alex Reynolds4, Shane Neph4, Richard Humbert4, R. Scott Hansen4, Marella F. T. R. de Bruijn22, Licia Selleri23, Alexander Y. Rudensky24, Steven Z. Josefowicz24, Robert M. Samstein24, Evan E. Eichler4, Stuart H. Orkin25, Dana N. Levasseur26, Thalia Papayannopoulou4, Kai Hsin Chang4, Arthur I. Skoultchi27, Srikanta Gosh27, Christine M. Disteche4, Piper M. Treuting4, Yanli Wang1, Mitchell J. Weiss, Gerd A. Blobel28, Xiaoyi Cao2, Sheng Zhong2, Ting Wang29, Peter J. Good30, Rebecca F. Lowdon30, Rebecca F. Lowdon29, Leslie B. Adams30, Leslie B. Adams31, Xiao Qiao Zhou30, Michael J. Pazin30, Elise A. Feingold30, Barbara J. Wold9, James Taylor11, Ali Mortazavi15, Sherman M. Weissman18, John A. Stamatoyannopoulos4, Michael Snyder3, Roderic Guigó, Thomas R. Gingeras8, David M. Gilbert6, Ross C. Hardison1, Michael A. Beer20, Bing Ren2 
20 Nov 2014-Nature
TL;DR: The mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types as mentioned in this paper.
Abstract: The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases

1,335 citations

Journal ArticleDOI
11 Jun 2015-Nature
TL;DR: In this paper, the authors generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms.
Abstract: We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ∼8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ∼24,000-year-old Siberian. By ∼6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ∼4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ∼75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ∼3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.

1,332 citations

Journal ArticleDOI
TL;DR: Scripture, a method to reconstruct the transcriptome of a mammalian cell using only RNA-Seq reads and the genome sequence, is presented and the power of ab initio reconstruction is demonstrated to render a comprehensive picture of mammalian transcriptomes.
Abstract: High-throughput sequencing of total cellular RNA by RNA-Seq promises rapid reconstruction of spliced transcripts in a cell population. Guttman et al. accomplish this using only paired-end RNA-seq data and an unannotated genome sequence, and apply the method to better define many new, conserved long intergenic noncoding RNAs (lincRNAs).

1,326 citations


Authors

Showing all 7146 results

NameH-indexPapersCitations
Eric S. Lander301826525976
Albert Hofman2672530321405
Frank B. Hu2501675253464
David J. Hunter2131836207050
Kari Stefansson206794174819
Mark J. Daly204763304452
Lewis C. Cantley196748169037
Matthew Meyerson194553243726
Gad Getz189520247560
Stacey Gabriel187383294284
Stuart H. Orkin186715112182
Ralph Weissleder1841160142508
Chris Sander178713233287
Michael I. Jordan1761016216204
Richard A. Young173520126642
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202337
2022627
20211,727
20201,534
20191,364
20181,107