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Find video protocols related to scientific articles indexed in Pubmed.
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
Stephan Ripke, Colm O'Dushlaine, Kimberly Chambert, Jennifer L Moran, Anna K Kähler, Susanne Akterin, Sarah E Bergen, Ann L Collins, James J Crowley, Menachem Fromer, Yunjung Kim, Sang Hong Lee, Patrik K E Magnusson, Nick Sanchez, Eli A Stahl, Stephanie Williams, Naomi R Wray, Kai Xia, Francesco Bettella, Anders D Borglum, Brendan K Bulik-Sullivan, Paul Cormican, Nick Craddock, Christiaan de Leeuw, Naser Durmishi, Michael Gill, Vera Golimbet, Marian L Hamshere, Peter Holmans, David M Hougaard, Kenneth S Kendler, Kuang Lin, Derek W Morris, Ole Mors, Preben B Mortensen, Benjamin M Neale, Francis A O'Neill, Michael J Owen, Milica Pejović Milovančević, Danielle Posthuma, John Powell, Alexander L Richards, Brien P Riley, Douglas Ruderfer, Dan Rujescu, Engilbert Sigurdsson, Teimuraz Silagadze, August B Smit, Hreinn Stefansson, Stacy Steinberg, Jaana Suvisaari, Sarah Tosato, Matthijs Verhage, James T Walters, , Douglas F Levinson, Pablo V Gejman, Claudine Laurent, Bryan J Mowry, Michael C O'Donovan, Ann E Pulver, Sibylle G Schwab, Dieter B Wildenauer, Frank Dudbridge, Jianxin Shi, Margot Albus, Madeline Alexander, Dominique Campion, David Cohen, Dimitris Dikeos, Jubao Duan, Peter Eichhammer, Stephanie Godard, Mark Hansen, F Bernard Lerer, Kung-Yee Liang, Wolfgang Maier, Jacques Mallet, Deborah A Nertney, Gerald Nestadt, Nadine Norton, George N Papadimitriou, Robert Ribble, Alan R Sanders, Jeremy M Silverman, Dermot Walsh, Nigel M Williams, Brandon Wormley, Maria J Arranz, Steven Bakker, Stephan Bender, Elvira Bramon, David Collier, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Assen Jablensky, René S Kahn, Luba Kalaydjieva, Stephen Lawrie, Cathryn M Lewis, Don H Linszen, Ignacio Mata, Andrew McIntosh, Robin M Murray, Roel A Ophoff, Jim van Os, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Peter Donnelly, Inês Barroso, Jenefer M Blackwell, Matthew A Brown, Juan P Casas, Aiden P Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S Markus, Christopher G Mathew, Colin N A Palmer, Robert Plomin, Anna Rautanen, Stephen J Sawcer, Richard C Trembath, Ananth C Viswanathan, Nicholas W Wood, Chris C A Spencer, Gavin Band, Celine Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Sarah E Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T McCann, Jennifer Liddle, Simon C Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew J Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Mark I McCarthy, Kari Stefansson, Edward Scolnick, Shaun Purcell, Steven A McCarroll, Pamela Sklar, Christina M Hultman, Patrick F Sullivan.
Nat. Genet.
PUBLISHED: 08-01-2013
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Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
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The zebrafish reference genome sequence and its relationship to the human genome.
Kerstin Howe, Matthew D Clark, Carlos F Torroja, James Torrance, Camille Berthelot, Matthieu Muffato, John E Collins, Sean Humphray, Karen McLaren, Lucy Matthews, Stuart McLaren, Ian Sealy, Mario Caccamo, Carol Churcher, Carol Scott, Jeffrey C Barrett, Romke Koch, Gerd-Jörg Rauch, Simon White, William Chow, Britt Kilian, Leonor T Quintais, José A Guerra-Assunção, Yi Zhou, Yong Gu, Jennifer Yen, Jan-Hinnerk Vogel, Tina Eyre, Seth Redmond, Ruby Banerjee, Jianxiang Chi, Beiyuan Fu, Elizabeth Langley, Sean F Maguire, Gavin K Laird, David Lloyd, Emma Kenyon, Sarah Donaldson, Harminder Sehra, Jeff Almeida-King, Jane Loveland, Stephen Trevanion, Matt Jones, Mike Quail, Dave Willey, Adrienne Hunt, John Burton, Sarah Sims, Kirsten McLay, Bob Plumb, Joy Davis, Chris Clee, Karen Oliver, Richard Clark, Clare Riddle, David Elliot, David Eliott, Glen Threadgold, Glenn Harden, Darren Ware, Sharmin Begum, Beverley Mortimore, Beverly Mortimer, Giselle Kerry, Paul Heath, Benjamin Phillimore, Alan Tracey, Nicole Corby, Matthew Dunn, Christopher Johnson, Jonathan Wood, Susan Clark, Sarah Pelan, Guy Griffiths, Michelle Smith, Rebecca Glithero, Philip Howden, Nicholas Barker, Christine Lloyd, Christopher Stevens, Joanna Harley, Karen Holt, Georgios Panagiotidis, Jamieson Lovell, Helen Beasley, Carl Henderson, Daria Gordon, Katherine Auger, Deborah Wright, Joanna Collins, Claire Raisen, Lauren Dyer, Kenric Leung, Lauren Robertson, Kirsty Ambridge, Daniel Leongamornlert, Sarah McGuire, Ruth Gilderthorp, Coline Griffiths, Deepa Manthravadi, Sarah Nichol, Gary Barker, Siobhan Whitehead, Michael Kay, Jacqueline Brown, Clare Murnane, Emma Gray, Matthew Humphries, Neil Sycamore, Darren Barker, David Saunders, Justene Wallis, Anne Babbage, Sian Hammond, Maryam Mashreghi-Mohammadi, Lucy Barr, Sancha Martin, Paul Wray, Andrew Ellington, Nicholas Matthews, Matthew Ellwood, Rebecca Woodmansey, Graham Clark, James D Cooper, James Cooper, Anthony Tromans, Darren Grafham, Carl Skuce, Richard Pandian, Robert Andrews, Elliot Harrison, Andrew Kimberley, Jane Garnett, Nigel Fosker, Rebekah Hall, Patrick Garner, Daniel Kelly, Christine Bird, Sophie Palmer, Ines Gehring, Andrea Berger, Christopher M Dooley, Zübeyde Ersan-Ürün, Cigdem Eser, Horst Geiger, Maria Geisler, Lena Karotki, Anette Kirn, Judith Konantz, Martina Konantz, Martina Oberländer, Silke Rudolph-Geiger, Mathias Teucke, Christa Lanz, Günter Raddatz, Kazutoyo Osoegawa, Baoli Zhu, Amanda Rapp, Sara Widaa, Cordelia Langford, Fengtang Yang, Stephan C Schuster, Nigel P Carter, Jennifer Harrow, Zemin Ning, Javier Herrero, Steve M J Searle, Anton Enright, Robert Geisler, Ronald H A Plasterk, Charles Lee, Monte Westerfield, Pieter J de Jong, Leonard I Zon, John H Postlethwait, Christiane Nüsslein-Volhard, Tim J P Hubbard, Hugues Roest Crollius, Jane Rogers, Derek L Stemple.
Nature
PUBLISHED: 03-21-2013
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Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
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Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.
David M Evans, Chris C A Spencer, Jennifer J Pointon, Zhan Su, David Harvey, Grazyna Kochan, Udo Oppermann, Udo Opperman, Alexander Dilthey, Matti Pirinen, Millicent A Stone, Louise Appleton, Loukas Moutsianas, Loukas Moutsianis, Stephen Leslie, Tom Wordsworth, Tony J Kenna, Tugce Karaderi, Gethin P Thomas, Michael M Ward, Michael H Weisman, Claire Farrar, Linda A Bradbury, Patrick Danoy, Robert D Inman, Walter Maksymowych, Dafna Gladman, Proton Rahman, , Ann Morgan, Helena Marzo-Ortega, Paul Bowness, Karl Gaffney, J S Hill Gaston, Malcolm Smith, Jacome Bruges-Armas, Ana-Rita Couto, Rosa Sorrentino, Fabiana Paladini, Manuel A Ferreira, Huji Xu, Yu Liu, Lei Jiang, Carlos López-Larrea, Roberto Díaz-Peña, Antonio López-Vázquez, Tetyana Zayats, Gavin Band, Celine Bellenguez, Hannah Blackburn, Jenefer M Blackwell, Elvira Bramon, Suzannah J Bumpstead, Juan P Casas, Aiden Corvin, Nicholas Craddock, Panos Deloukas, Serge Dronov, Audrey Duncanson, Sarah Edkins, Colin Freeman, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E Hunt, Janusz Jankowski, Alagurevathi Jayakumar, Cordelia Langford, Jennifer Liddle, Hugh S Markus, Christopher G Mathew, Owen T McCann, Mark I McCarthy, Colin N A Palmer, Leena Peltonen, Robert Plomin, Simon C Potter, Anna Rautanen, Radhi Ravindrarajah, Michelle Ricketts, Nilesh Samani, Stephen J Sawcer, Amy Strange, Richard C Trembath, Ananth C Viswanathan, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Nicholas W Wood, Gilean McVean, John D Reveille, B Paul Wordsworth, Matthew A Brown, Peter Donnelly.
Nat. Genet.
PUBLISHED: 12-21-2011
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Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
, Stephen Sawcer, Garrett Hellenthal, Matti Pirinen, Chris C A Spencer, Nikolaos A Patsopoulos, Loukas Moutsianas, Alexander Dilthey, Zhan Su, Colin Freeman, Sarah E Hunt, Sarah Edkins, Emma Gray, David R Booth, Simon C Potter, An Goris, Gavin Band, Annette Bang Oturai, Amy Strange, Janna Saarela, Celine Bellenguez, Bertrand Fontaine, Matthew Gillman, Bernhard Hemmer, Rhian Gwilliam, Frauke Zipp, Alagurevathi Jayakumar, Roland Martin, Stephen Leslie, Stanley Hawkins, Eleni Giannoulatou, Sandra D'Alfonso, Hannah Blackburn, Filippo Martinelli Boneschi, Jennifer Liddle, Hanne F Harbo, Marc L Perez, Anne Spurkland, Matthew J Waller, Marcin P Mycko, Michelle Ricketts, Manuel Comabella, Naomi Hammond, Ingrid Kockum, Owen T McCann, Maria Ban, Pamela Whittaker, Anu Kemppinen, Paul Weston, Clive Hawkins, Sara Widaa, John Zajicek, Serge Dronov, Neil Robertson, Suzannah J Bumpstead, Lisa F Barcellos, Rathi Ravindrarajah, Roby Abraham, Lars Alfredsson, Kristin Ardlie, Cristin Aubin, Amie Baker, Katharine Baker, Sergio E Baranzini, Laura Bergamaschi, Roberto Bergamaschi, Allan Bernstein, Achim Berthele, Mike Boggild, Jonathan P Bradfield, David Brassat, Simon A Broadley, Dorothea Buck, Helmut Butzkueven, Ruggero Capra, William M Carroll, Paola Cavalla, Elisabeth G Celius, Sabine Cepok, Rosetta Chiavacci, Françoise Clerget-Darpoux, Katleen Clysters, Giancarlo Comi, Mark Cossburn, Isabelle Cournu-Rebeix, Mathew B Cox, Wendy Cozen, Bruce A C Cree, Anne H Cross, Daniele Cusi, Mark J Daly, Emma Davis, Paul I W de Bakker, Marc Debouverie, Marie Beatrice D'hooghe, Katherine Dixon, Rita Dobosi, Bénédicte Dubois, David Ellinghaus, Irina Elovaara, Federica Esposito, Claire Fontenille, Simon Foote, Andre Franke, Daniela Galimberti, Angelo Ghezzi, Joseph Glessner, Refujia Gomez, Olivier Gout, Colin Graham, Struan F A Grant, Franca Rosa Guerini, Hakon Hakonarson, Per Hall, Anders Hamsten, Hans-Peter Hartung, Rob N Heard, Simon Heath, Jeremy Hobart, Muna Hoshi, Carmen Infante-Duarte, Gillian Ingram, Wendy Ingram, Talat Islam, Maja Jagodic, Michael Kabesch, Allan G Kermode, Trevor J Kilpatrick, Cecilia Kim, Norman Klopp, Keijo Koivisto, Malin Larsson, Mark Lathrop, Jeannette S Lechner-Scott, Maurizio A Leone, Virpi Leppä, Ulrika Liljedahl, Izaura Lima Bomfim, Robin R Lincoln, Jenny Link, Jianjun Liu, Aslaug R Lorentzen, Sara Lupoli, Fabio Macciardi, Thomas Mack, Mark Marriott, Vittorio Martinelli, Deborah Mason, Jacob L McCauley, Frank Mentch, Inger-Lise Mero, Tania Mihalova, Xavier Montalban, John Mottershead, Kjell-Morten Myhr, Paola Naldi, William Ollier, Alison Page, Aarno Palotie, Jean Pelletier, Laura Piccio, Trevor Pickersgill, Fredrik Piehl, Susan Pobywajlo, Hong L Quach, Patricia P Ramsay, Mauri Reunanen, Richard Reynolds, John D Rioux, Mariaemma Rodegher, Sabine Roesner, Justin P Rubio, Ina-Maria Rückert, Marco Salvetti, Erika Salvi, Adam Santaniello, Catherine A Schaefer, Stefan Schreiber, Christian Schulze, Rodney J Scott, Finn Sellebjerg, Krzysztof W Selmaj, David Sexton, Ling Shen, Brigid Simms-Acuna, Sheila Skidmore, Patrick M A Sleiman, Cathrine Smestad, Per Soelberg Sørensen, Helle Bach Søndergaard, Jim Stankovich, Richard C Strange, Anna-Maija Sulonen, Emilie Sundqvist, Ann-Christine Syvänen, Francesca Taddeo, Bruce Taylor, Jenefer M Blackwell, Pentti Tienari, Elvira Bramon, Ayman Tourbah, Matthew A Brown, Ewa Tronczynska, Juan P Casas, Niall Tubridy, Aiden Corvin, Jane Vickery, Janusz Jankowski, Pablo Villoslada, Hugh S Markus, Kai Wang, Christopher G Mathew, James Wason, Colin N A Palmer, H-Erich Wichmann, Robert Plomin, Ernest Willoughby, Anna Rautanen, Juliane Winkelmann, Michael Wittig, Richard C Trembath, Jacqueline Yaouanq, Ananth C Viswanathan, Haitao Zhang, Nicholas W Wood, Rebecca Zuvich, Panos Deloukas, Cordelia Langford, Audrey Duncanson, Jorge R Oksenberg, Margaret A Pericak-Vance, Jonathan L Haines, Tomas Olsson, Jan Hillert, Adrian J Ivinson, Philip L De Jager, Leena Peltonen, Graeme J Stewart, David A Hafler, Stephen L Hauser, Gil McVean, Peter Donnelly, Alastair Compston.
Nature
PUBLISHED: 02-04-2011
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Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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GLO1-A novel amplified gene in human cancer.
Genes Chromosomes Cancer
PUBLISHED: 06-15-2010
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To identify a novel amplified cancer gene a systematic screen of 975 human cancer DNA samples, 750 cell lines and 225 primary tumors, using the Affymetrix 10K SNP microarray was undertaken. The screen identified 193 amplicons. A previously uncharacterized amplicon located on 6p21.2 whose 1 Mb minimal common amplified region contained eight genes (GLO1, DNAH8, GLP1R, C6orf64, KCNK5, KCNK17, KCNK16, and C6orf102) was further investigated to determine which gene(s) are the biological targets of this amplicon. Real time quantitative PCR (qPCR) analysis of all amplicon 6p21.2 genes in 618 human cancer cell lines identified GLO1, encoding glyoxalase 1, to be the most frequently amplified gene [twofold or greater amplification in 8.4% (49/536) of cancers]. Also the association between amplification and overexpression was greatest for GLO1. RNAi knockdown of GLO1 had the greatest and most consistent impact on cell accumulation and apoptosis. Cell lines with GLO1 amplification were more sensitive to inhibition of GLO1 by bromobenzylglutathione cyclopentyl diester (BBGC). Subsequent qPCR of 520 primary tumor samples identified twofold and greater amplification of GLO1 in 8/37 (22%) of breast, 12/71 (17%) of sarcomas, 6/53 (11.3%) of nonsmall cell lung, 2/23 (8.7%) of bladder, 6/93 (6.5%) of renal and 5/83 (6%) of gastric cancers. Amplification of GLO1 was rare in colon cancer (1/35) and glioma (1/94). Collectively the results indicate that GLO1 is at least one of the targets of gene amplification on 6p21.2 and may represent a useful target for therapy in cancers with GLO1 amplification.
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Signatures of mutation and selection in the cancer genome.
Nature
PUBLISHED: 02-19-2010
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The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery.
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PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data.
Biostatistics
PUBLISHED: 10-15-2009
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High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell lines, enabling inference upon a number of features of biological interest. These data and the coded algorithm are freely available for download.
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Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
Nat. Genet.
PUBLISHED: 08-17-2009
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Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P < 1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.
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Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer.
Nat. Genet.
PUBLISHED: 02-06-2009
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Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase gene UTX, pointing to histone H3 lysine methylation deregulation in multiple tumor types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene.
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A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.
Nat. Genet.
PUBLISHED: 02-02-2009
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Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR), the largest direct screen for constitutional disease-causing mutations thus far reported. The screen has discovered nine genes implicated in XLMR, including SYP, ZNF711 and CASK reported here, confirming the power of this strategy. The study has, however, also highlighted issues confronting whole-genome sequencing screens, including the observation that loss of function of 1% or more of X-chromosome genes is compatible with apparently normal existence.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.