5 results on '"T. Dan Andrews"'
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2. DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project.
- Author
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Vardhman K Rakyan, Thomas Hildmann, Karen L Novik, Jörn Lewin, Jörg Tost, Antony V Cox, T Dan Andrews, Kevin L Howe, Thomas Otto, Alexander Olek, Judith Fischer, Ivo G Gut, Kurt Berlin, and Stephan Beck
- Subjects
Biology (General) ,QH301-705.5 - Abstract
The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data.
- Published
- 2004
- Full Text
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3. IgD attenuates the IgM-induced anergy response in transitional and mature B cells
- Author
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Mehmet Yabas, Keisuke Horikawa, Clara Young, Samuel Perotti, Christopher C. Goodnow, Zahra Sabouri, Samantha Lambe, Hannes Bergmann, Carla M. Roots, Emily Spierings, Peter Humburg, Joanne H. Reed, T. Dan Andrews, Matthew A. Field, and Anselm Enders
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0301 basic medicine ,Male ,Science ,Cell ,General Physics and Astronomy ,Receptors, Antigen, B-Cell ,chemical and pharmacologic phenomena ,Lymphocyte Activation ,Immunoglobulin D ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antibody Repertoire ,stomatognathic system ,hemic and lymphatic diseases ,medicine ,Animals ,Calcium Signaling ,Receptor ,Calcium signaling ,Clonal Anergy ,Messenger RNA ,B-Lymphocytes ,Multidisciplinary ,biology ,Clonal anergy ,Gene Expression Profiling ,RNA ,hemic and immune systems ,General Chemistry ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Self Tolerance ,Immunoglobulin M ,Immunology ,Mutation ,biology.protein ,Syndecan-1 ,030215 immunology - Abstract
Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire., Self-reactive B cells that are anergic express mainly IgD, yet the function of IgD is not clear. Here the authors analyse primary B cells from mice to show that IgD signalling attenuates self-antigen induced gene expression and promotes survival of anergic B cells that might go on to reactivate to foreign antigens and mutate away from self-reactivity.
- Published
- 2016
4. Genome sequence of the Brown Norway rat yields insights into mammalian evolution
- Author
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Rui Chen, George M. Weinstock, Cynthia Pfannkoch, Chris P. Ponting, Mark S. Guyer, Manuel L. Gonzalez-Garay, James Taylor, Yixin Chen, Eric D. Green, Simon Cawley, Jo Gullings-Handley, Granger G. Sutton, Jose M. Duarte, Stephen M. J. Searle, Laura Elnitski, Aleksandar Milosavljevic, Alicia Hawes, Stephen C. Mockrin, Oliver Delgado, Shannon Dugan-Rocha, Christine Deramo, Dean Pasko, Marina Alexandersson, Eitan E. Winter, Robert W. Blakesley, Donna Karolchik, Huajun Wang, David Shteynberg, Diane M. Dunn, Carlos López-Otín, Abel Ureta-Vidal, Jia Qian Wu, A. Glodek, Shan Yang, Natasja Wye, Sue Daniels, Keita Geer, Arian F.A. Smit, Jozef Lazar, Pallavi Eswara, Carl Fosler, Douglas Smith, Martin Krzywinski, Uma Mudunuri, George Miner, Herbert Schulz, Angie S. Hinrichs, Manimozhiyan Arumugam, Josep F. Abril, Ursula Vitt, Andrei Volkov, Peter J. Tonellato, Von Bing Yap, Bingshan Li, Jyoti Shetty, Ian Bosdet, Evgeny M. Zdobnov, San Diego Glenn Tesler, Chris Fjell, Yi Zhang, Francis S. Collins, Serafim Batzoglou, Robert Baertsch, Laura Clarke, David Neil Cooper, Carrie Mathewson, Diana L. Kolbe, Kate R. Rosenbloom, Valerie Curwen, Bret A. Payseur, Gerard G. Bouffard, Michael R. Brent, Barbara J. Trask, Scott A. Beatson, Sourav Chatterji, Francisco Camara, Detlev Ganten, Andrew R. Jackson, Claire M. Fraser, Klaus Lindpaintner, Yue Liu, Mark Raymond Adams, Robert A. Holt, Erik Gustafson, Hiram Clawson, Michael L. Metzker, John Douglas Mcpherson, Gregory M. Cooper, Martin S. Taylor, Scott Schwartz, Hui Huang, Darryl Gietzen, Patrick Cahill, Geoffrey Okwuonu, Sandra Hines, J. Craig Venter, Jan Monti, David Steffen, Marco A. Marra, Arnold Kana, Richard D. Emes, Asim Sarosh Siddiqui, Erica Sodergren, Mario Caccamo, Jim Wingrove, Richard R. Copley, Leo Goodstadt, Francesca Chiaromonte, Davinder Virk, Kirt Martin, Colin N. Dewey, Xiang Qin, T. Dan Andrews, K. James Durbin, Michael P. McLeod, Susan Bromberg, Pavel A. Pevzner, Petra Brandt, Austin J. Cooney, Don Jennings, Baoli Zhu, Lynn Doucette-Stamm, Heather Trumbower, Eray Tüzün, Kristian Stevens, Norbert Hubner, Young-Ae Lee, Zhiping Gu, Harold Riethman, Xose S. Puente, Cynthia Sitter, Michael Brudno, Gerald Nyakatura, Oliver Hummel, Caleb Webber, Olivier Couronne, Kim Fechtel, W. J. Kent, Zhengdong D. Zhang, Xing Zhi Song, Matt Weirauch, Ewan Birney, Richard A. Gibbs, William C. Nierman, Anne E. Kwitek, Alexander Poliakov, Mary Barnstead, Jeanette Schmidt, Yanru Ren, Howard J. Jacob, Kateryna D. Makova, Edward M. Rubin, Susan Old, Trixie Nguyen, Arend Sidow, Nicolas Bray, Hong Mei Lee, Lisa M. D'Souza, Heinz Himmelbauer, Cara Woodwark, Peter G. Amanatides, Paul Havlak, Janet M. Young, Eduardo Eyras, Thomas Kreitler, Heming Xing, Sofiya Shatsman, Kushal Chakrabarti, Stephen Rice, Cheryl A. Evans, Kim C. Worley, Peter D. Stenson, Rachel Gill, Pieter J. de Jong, Jacqueline E. Schein, Lior Pachter, Steve Ferriera, Santa Cruz David Haussler, Ross C. Hardison, Holly Baden-Tillson, Margaret Adetobi, Krishna M. Roskin, Guillaume Bourque, Eric A. Stone, Emmanuel Mongin, Michele Clamp, Margaret Morgan, Richard Durbin, Cathy Riemer, Anton Nekrutenko, Mikita Suyama, Soo H. Chin, Kenneth J. Kalafus, Anat Caspi, Donna M. Muzny, Inna Dubchak, Shaying Zhao, Sofyia Abramzon, Michael I. Jensen-Seaman, Steven E. Scherer, Lora Lewis, M. Mar Albà, Terrence S. Furey, Peer Bork, Trevor Woodage, David A. Wheeler, Hans Lehrach, Graham R. Scott, Bin Ma, Paula E. Burch, Robert B. Weiss, Kazutoyo Osoegawa, Evan E. Eichler, Amy Egan, Webb Miller, Cheryl L. Kraft, Steven J.M. Jones, Jeffrey A. Bailey, Roderic Guigó, David Torrents, Heike Zimdahl, Adam Felsenfeld, Jane Peterson, Simon N. Twigger, Claudia Goesele, Keith Weinstock, Minmei Hou, and Zdobnov, Evgeny
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Male ,Models, Molecular ,Mammalian Genetics ,RNA, Untranslated ,Retroelements ,Sequence analysis ,Gene prediction ,Centromere ,Genomics ,Biology ,Regulatory Sequences, Nucleic Acid ,Genome ,DNA, Mitochondrial ,Polymorphism, Single Nucleotide ,Rat Genome Database ,Evolution, Molecular ,Mice ,Gene Duplication ,Rats, Inbred BN ,Animals ,Humans ,ddc:576.5 ,Gene ,Whole genome sequencing ,Genetics ,Base Composition ,Multidisciplinary ,Sequence Analysis, DNA ,Telomere ,Chromosomes, Mammalian ,Introns ,Rats ,Evolutionary biology ,Mutagenesis ,DNA Transposable Elements ,CpG Islands ,RNA Splice Sites - Abstract
The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
- Published
- 2003
5. Finding new immune regulatory genes by ENU mutagenesis
- Author
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Ed Bertram, Christopher C. Goodnow, Yovina Sontani, Geoff Sjollema, Lisa A. Miosge, Mathew Field, Hannes Bergmann, Anselm Enders, Bhavani Balakishnan, Mehmet Yabas, Stuart H Read, T. Dan Andrews, and Belinda Whittle
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Medicine(all) ,Genetics ,Mutation ,Biochemistry, Genetics and Molecular Biology(all) ,Mutant ,Invited Speaker Presentation ,Mutagenesis (molecular biology technique) ,General Medicine ,Biology ,medicine.disease_cause ,Phenotype ,Genome ,General Biochemistry, Genetics and Molecular Biology ,medicine ,Missense mutation ,Gene ,Regulator gene - Abstract
IntroductionThe Thousand Genomes Project has revealed the extraor-dinary scale of human genetic variation such as each per-son inherits ~12,000 protein-changing single nucleotidevariations (SNVs) including up to 100 premature STOPcodons creating an immense challenge to investigate thephysiological consequence of this type of genetic variationin experimental animals.AimTo develop a new strategy to meet this need by usingwhole exome capture, massively parallel DNA sequenc-ing and computational analysis to sensitively and specifi-cally identify 40-50 de novo mis-sense SNV mutationsspread across the genome of individual offspring fromENU-mutagenized C57BL/6 mice [1].ResultsIn this presentation we demonstrate how direct se-quencing of animals with indepe ndent defects in B celldevelopment resulted in the identification of the causa-tive mutation both in genes of previously known andunknown function without meiotic mapping. Thisapproach has resulted in the identification of a newphospholipid transport pathway that is crucial for nor-mal B cell development in the bone marrow [2] and therealization that an endopeptidase of previously unknownin vivo function is essential for normal processing ofMHC invariant chain and terminal B cell and DCmaturation.By sequencing animals from defined strains and alsofounder animals of ENU mutant pedigrees two generationsbefore the phenotypic screens we have started to build adatabase of missense mutations containing currently closeto 7000 mutations in mouse pedigrees actively breedingand immediately available for experimental analysis.All data is made available from the missense variant data-base (pb.apf.edu.au/phenbank).ConclusionThis approach transforms mammalian experimentalgenetics and opens up an unparalleled source for experi-mental models of human disease and validation of humandisease associated SNVs.
- Published
- 2012
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