scispace - formally typeset
Search or ask a question
Institution

Wellcome Trust Sanger Institute

NonprofitCambridge, 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.


Papers
More filters
Journal ArticleDOI
TL;DR: This work has examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites, and over one-third of GENCODE protein-Coding genes aresupported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas.
Abstract: The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

4,281 citations

Journal ArticleDOI
23 Nov 2006-Nature
TL;DR: A first-generation CNV map of the human genome is constructed through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia, underscoring the importance of CNV in genetic diversity and evolution and the utility of this resource for genetic disease studies.
Abstract: Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

4,275 citations

Journal ArticleDOI
11 May 2007-Science
TL;DR: A genome-wide search for type 2 diabetes–susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI).
Abstract: Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.

4,184 citations

Journal ArticleDOI
Luke Jostins1, Stephan Ripke2, Rinse K. Weersma3, Richard H. Duerr4, Dermot P.B. McGovern5, Ken Y. Hui6, James Lee7, L. Philip Schumm8, Yashoda Sharma6, Carl A. Anderson1, Jonah Essers9, Mitja Mitrovic3, Kaida Ning6, Isabelle Cleynen10, Emilie Theatre11, Sarah L. Spain12, Soumya Raychaudhuri9, Philippe Goyette13, Zhi Wei14, Clara Abraham6, Jean-Paul Achkar15, Tariq Ahmad16, Leila Amininejad17, Ashwin N. Ananthakrishnan9, Vibeke Andersen18, Jane M. Andrews19, Leonard Baidoo4, Tobias Balschun20, Peter A. Bampton21, Alain Bitton22, Gabrielle Boucher13, Stephan Brand23, Carsten Büning24, Ariella Cohain25, Sven Cichon26, Mauro D'Amato27, Dirk De Jong3, Kathy L Devaney9, Marla Dubinsky5, Cathryn Edwards28, David Ellinghaus20, Lynnette R. Ferguson29, Denis Franchimont17, Karin Fransen3, Richard B. Gearry30, Michel Georges11, Christian Gieger, Jürgen Glas22, Talin Haritunians5, Ailsa Hart31, Christopher J. Hawkey32, Matija Hedl6, Xinli Hu9, Tom H. Karlsen33, Limas Kupčinskas34, Subra Kugathasan35, Anna Latiano36, Debby Laukens37, Ian C. Lawrance38, Charlie W. Lees39, Edouard Louis11, Gillian Mahy40, John C. Mansfield41, Angharad R. Morgan29, Craig Mowat42, William G. Newman43, Orazio Palmieri36, Cyriel Y. Ponsioen44, Uroš Potočnik45, Natalie J. Prescott6, Miguel Regueiro4, Jerome I. Rotter5, Richard K Russell46, Jeremy D. Sanderson47, Miquel Sans, Jack Satsangi39, Stefan Schreiber20, Lisa A. Simms48, Jurgita Sventoraityte34, Stephan R. Targan, Kent D. Taylor5, Mark Tremelling49, Hein W. Verspaget50, Martine De Vos37, Cisca Wijmenga3, David C. Wilson39, Juliane Winkelmann51, Ramnik J. Xavier9, Sebastian Zeissig20, Bin Zhang25, Clarence K. Zhang6, Hongyu Zhao6, Mark S. Silverberg52, Vito Annese, Hakon Hakonarson53, Steven R. Brant54, Graham L. Radford-Smith55, Christopher G. Mathew12, John D. Rioux13, Eric E. Schadt25, Mark J. Daly2, Andre Franke20, Miles Parkes7, Severine Vermeire10, Jeffrey C. Barrett1, Judy H. Cho6 
Wellcome Trust Sanger Institute1, Broad Institute2, University of Groningen3, University of Pittsburgh4, Cedars-Sinai Medical Center5, Yale University6, University of Cambridge7, University of Chicago8, Harvard University9, Katholieke Universiteit Leuven10, University of Liège11, King's College London12, Université de Montréal13, New Jersey Institute of Technology14, Cleveland Clinic15, Peninsula College of Medicine and Dentistry16, Université libre de Bruxelles17, Aarhus University18, University of Adelaide19, University of Kiel20, Flinders University21, McGill University22, Ludwig Maximilian University of Munich23, Charité24, Icahn School of Medicine at Mount Sinai25, University of Bonn26, Karolinska Institutet27, Torbay Hospital28, University of Auckland29, Christchurch Hospital30, Imperial College London31, Queen's University32, University of Oslo33, Lithuanian University of Health Sciences34, Emory University35, Casa Sollievo della Sofferenza36, Ghent University37, University of Western Australia38, University of Edinburgh39, Queensland Health40, Newcastle University41, University of Dundee42, University of Manchester43, University of Amsterdam44, University of Maribor45, Royal Hospital for Sick Children46, Guy's and St Thomas' NHS Foundation Trust47, QIMR Berghofer Medical Research Institute48, Norfolk and Norwich University Hospital49, Leiden University50, Technische Universität München51, University of Toronto52, University of Pennsylvania53, Johns Hopkins University54, University of Queensland55
01 Nov 2012-Nature
TL;DR: A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
Abstract: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

4,094 citations

Journal ArticleDOI
06 Nov 2008-Nature
TL;DR: An approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost is reported, effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.
Abstract: DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.

3,802 citations


Authors

Showing all 4058 results

NameH-indexPapersCitations
Nicholas J. Wareham2121657204896
Gonçalo R. Abecasis179595230323
Panos Deloukas162410154018
Michael R. Stratton161443142586
David W. Johnson1602714140778
Michael John Owen1601110135795
Naveed Sattar1551326116368
Robert E. W. Hancock15277588481
Julian Parkhill149759104736
Nilesh J. Samani149779113545
Michael Conlon O'Donovan142736118857
Jian Yang1421818111166
Christof Koch141712105221
Andrew G. Clark140823123333
Stylianos E. Antonarakis13874693605
Network Information
Related Institutions (5)
Broad Institute
11.6K papers, 1.5M citations

96% related

Howard Hughes Medical Institute
34.6K papers, 5.2M citations

95% related

Laboratory of Molecular Biology
24.2K papers, 2.1M citations

94% related

Salk Institute for Biological Studies
13.1K papers, 1.6M citations

93% related

National Institutes of Health
297.8K papers, 21.3M citations

93% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202270
2021836
2020810
2019854
2018764