Institution
Broad Institute
Nonprofit•Cambridge, 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.
Topics: Population, Genome-wide association study, Genome, Gene, Chromatin
Papers published on a yearly basis
Papers
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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
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Broad Institute1, Sainsbury Laboratory2, Ohio Agricultural Research and Development Center3, Uppsala University4, Wageningen University and Research Centre5, Virginia Bioinformatics Institute6, University of California, Riverside7, University of Aberdeen8, Scottish Crop Research Institute9, University of Warwick10, Agricultural Research Service11, Royal Institute of Technology12, Cornell University13, Oregon State University14, Lafayette College15, University of Glasgow16, Harvard University17, Delaware Biotechnology Institute18, North Carolina State University19, University of Delaware20, University of Tennessee21, University of Maryland, Baltimore22, Vanderbilt University23, College of Wooster24, Bowling Green State University25, Edinburgh Cancer Research Centre26, J. Craig Venter Institute27, Tel Aviv University28, University of Wisconsin-Madison29, University of Hohenheim30, University of Dundee31
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
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Pennsylvania State University1, University of California, San Diego2, Stanford University3, University of Washington4, University of Michigan5, Florida State University6, New College of Florida7, Cold Spring Harbor Laboratory8, California Institute of Technology9, University of Vienna10, Emory University11, Fred Hutchinson Cancer Research Center12, Massachusetts Institute of Technology13, Broad Institute14, University of California, Irvine15, University of California, Santa Cruz16, University of California, San Francisco17, Yale University18, University of Florida19, Johns Hopkins University20, University College London21, University of Oxford22, Cornell University23, Memorial Sloan Kettering Cancer Center24, Harvard University25, University of Iowa26, Yeshiva University27, University of Pennsylvania28, Washington University in St. Louis29, National Institutes of Health30, University of North Carolina at Chapel Hill31
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
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University of Adelaide1, Harvard University2, Broad Institute3, Howard Hughes Medical Institute4, University of Mainz5, Max Planck Society6, University of Tübingen7, Hungarian Academy of Sciences8, Stockholm University9, Facultad de Filosofía y Letras10, The Heritage Foundation11, University of Basel12, Autonomous University of Barcelona13, University of Valladolid14, Hartwick College15
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
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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
Name | H-index | Papers | Citations |
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Eric S. Lander | 301 | 826 | 525976 |
Albert Hofman | 267 | 2530 | 321405 |
Frank B. Hu | 250 | 1675 | 253464 |
David J. Hunter | 213 | 1836 | 207050 |
Kari Stefansson | 206 | 794 | 174819 |
Mark J. Daly | 204 | 763 | 304452 |
Lewis C. Cantley | 196 | 748 | 169037 |
Matthew Meyerson | 194 | 553 | 243726 |
Gad Getz | 189 | 520 | 247560 |
Stacey Gabriel | 187 | 383 | 294284 |
Stuart H. Orkin | 186 | 715 | 112182 |
Ralph Weissleder | 184 | 1160 | 142508 |
Chris Sander | 178 | 713 | 233287 |
Michael I. Jordan | 176 | 1016 | 216204 |
Richard A. Young | 173 | 520 | 126642 |