Institution
Wellcome Trust Sanger Institute
Nonprofit•Cambridge, United Kingdom•
About: Wellcome Trust Sanger Institute is a nonprofit organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Genome. The organization has 4009 authors who have published 9671 publications receiving 1224479 citations.
Topics: Population, Genome, Gene, Genome-wide association study, Genomics
Papers published on a yearly basis
Papers
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University of Hohenheim1, Beth Israel Deaconess Medical Center2, Broad Institute3, Icahn School of Medicine at Mount Sinai4, University of Oxford5, Vanderbilt University Medical Center6, University of Geneva7, Wellcome Trust Sanger Institute8, Harvard University9, University of Melbourne10, Baylor College of Medicine11, Boston Children's Hospital12, University of California, San Francisco13, National Institutes of Health14, Howard Hughes Medical Institute15, University of Washington16, University of Cambridge17
TL;DR: Progress is described in the study of human genetics, in which rapid advances in technology, foundational genomic resources and analytical tools have contributed to the understanding of the mechanisms responsible for many rare and common diseases and to preventative and therapeutic strategies for many of these conditions.
Abstract: A primary goal of human genetics is to identify DNA sequence variants that influence biomedical traits, particularly those related to the onset and progression of human disease. Over the past 25 years, progress in realizing this objective has been transformed by advances in technology, foundational genomic resources and analytical tools, and by access to vast amounts of genotype and phenotype data. Genetic discoveries have substantially improved our understanding of the mechanisms responsible for many rare and common diseases and driven development of novel preventative and therapeutic strategies. Medical innovation will increasingly focus on delivering care tailored to individual patterns of genetic predisposition.
356 citations
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TL;DR: A shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs is demonstrated, which is validated to produce an integrated map of fetal liver haematopoiesis.
Abstract: Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~140,000 liver and ~74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the impact of tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, NK and ILC precursors in the yolk sac. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for harnessing the therapeutic potential of HSC/MPPs.
356 citations
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University of Cambridge1, Francis Crick Institute2, The Royal Marsden NHS Foundation Trust3, National Health Service4, Wellcome Trust Sanger Institute5, University of the Basque Country6, University of Oxford7, Eötvös Loránd University8, University of Texas at Austin9, University of St Andrews10, University College London11
TL;DR: Analysis of whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred.
356 citations
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TL;DR: It is proposed that tissue-specific inclusion of disordered segments that contain binding motifs rewires interaction networks and signaling pathways and may contribute to functional versatility of proteins and increases the diversity of interaction networks across tissues.
356 citations
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TL;DR: This work systematically study the influence of flanking DNA sequence on repair outcome by measuring the edits generated by >40,000 guide RNAs (gRNAs) in synthetic constructs and uncover sequence determinants of the mutations produced and use these to derive a predictor of Cas9 editing outcomes.
Abstract: The DNA mutation produced by cellular repair of a CRISPR-Cas9-generated double-strand break determines its phenotypic effect. It is known that the mutational outcomes are not random, but depend on DNA sequence at the targeted location. Here we systematically study the influence of flanking DNA sequence on repair outcome by measuring the edits generated by >40,000 guide RNAs (gRNAs) in synthetic constructs. We performed the experiments in a range of genetic backgrounds and using alternative CRISPR-Cas9 reagents. In total, we gathered data for >109 mutational outcomes. The majority of reproducible mutations are insertions of a single base, short deletions or longer microhomology-mediated deletions. Each gRNA has an individual cell-line-dependent bias toward particular outcomes. We uncover sequence determinants of the mutations produced and use these to derive a predictor of Cas9 editing outcomes. Improved understanding of sequence repair will allow better design of gene editing experiments.
355 citations
Authors
Showing all 4058 results
Name | H-index | Papers | Citations |
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Nicholas J. Wareham | 212 | 1657 | 204896 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Panos Deloukas | 162 | 410 | 154018 |
Michael R. Stratton | 161 | 443 | 142586 |
David W. Johnson | 160 | 2714 | 140778 |
Michael John Owen | 160 | 1110 | 135795 |
Naveed Sattar | 155 | 1326 | 116368 |
Robert E. W. Hancock | 152 | 775 | 88481 |
Julian Parkhill | 149 | 759 | 104736 |
Nilesh J. Samani | 149 | 779 | 113545 |
Michael Conlon O'Donovan | 142 | 736 | 118857 |
Jian Yang | 142 | 1818 | 111166 |
Christof Koch | 141 | 712 | 105221 |
Andrew G. Clark | 140 | 823 | 123333 |
Stylianos E. Antonarakis | 138 | 746 | 93605 |