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GWAS of DNA Methylation Variation Within Imprinting Control Regions Suggests Parent-of-Origin Association
- Miguel E. Rentería, Marcel W. Coolen, Aaron L. Statham, R. Seong Min Choi, Wenjia Qu, Megan J. Campbell, Sara Smith, Anjali K. Henders, Grant W. Montgomery, Susan J. Clark, Nicholas G. Martin, Sarah E. Medland
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- Journal:
- Twin Research and Human Genetics / Volume 16 / Issue 4 / August 2013
- Published online by Cambridge University Press:
- 03 June 2013, pp. 767-781
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Imprinting control regions (ICRs) play a fundamental role in establishing and maintaining the non-random monoallelic expression of certain genes, via common regulatory elements such as non-coding RNAs and differentially methylated regions (DMRs) of DNA. We recently surveyed DNA methylation levels within four ICRs (H19-ICR, IGF2-DMR, KvDMR, and NESPAS-ICR) in whole-blood genomic DNA from 128 monozygotic (MZ) and 128 dizygotic (DZ) human twin pairs. Our analyses revealed high individual variation and intra-domain covariation in methylation levels across CpGs and emphasized the interaction between epigenetic variation and the underlying genetic sequence in a parent-of-origin fashion. Here, we extend our analysis to conduct two genome-wide screenings of single nucleotide polymorphisms (SNPs) underlying either intra-domain covariation or parent-of-origin-dependent association with methylation status at individual CpG sites located within ICRs. Although genome-wide significance was not surpassed due to sample size limitations, the most significantly associated SNPs found through multiple-trait genome-wide association (MQFAM) included the previously described rs10732516, which is located in the vicinity of the H19-ICR. Similarly, we identified an association between rs965808 and methylation status within the NESPAS-ICR. This SNP is positioned within an intronic region of the overlapping genes GNAS and GNAS-AS1, which are imprinted genes regulated by the NESPAS-ICR. Sixteen other SNPs located in regions apart from the analyzed regions displayed suggestive association with intra-domain methylation. Additionally, we identified 13 SNPs displaying parent-of-origin association with individual methylation sites through family-based association testing. In this exploratory study, we show the value and feasibility of using alternative GWAS approaches in the study of the interaction between epigenetic state and genetic sequence within imprinting regulatory domains. Despite the relatively small sample size, we identified a number of SNPs displaying suggestive association either in a domain-wide or in a parent-of-origin fashion. Nevertheless, these associations will require future experimental validation or replication in larger and independent samples.
Contributors
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- By Waiel Almoustadi, Brian J. Anderson, David B. Auyong, Michael Avidan, Michael J. Avram, Roland J. Bainton, Jeffrey R. Balser, Juliana Barr, W. Scott Beattie, Manfred Blobner, T. Andrew Bowdle, Walter A. Boyle, Eugene B. Campbell, Laura F. Cavallone, Mario Cibelli, C. Michael Crowder, Ola Dale, M. Frances Davies, Mark Dershwitz, George Despotis, Clifford S. Deutschman, Brian S. Donahue, Marcel E. Durieux, Thomas J. Ebert, Talmage D. Egan, Helge Eilers, E. Wesley Ely, Charles W. Emala, Alex S. Evers, Heidrun Fink, Pierre Foëx, Stuart A. Forman, Helen F. Galley, Josephine M. Garcia-Ferrer, Robert W. Gereau, Tony Gin, David Glick, B. Joseph Guglielmo, Dhanesh K. Gupta, Howard B. Gutstein, Robert G. Hahn, Greg B. Hammer, Brian P. Head, Helen Higham, Laureen Hill, Kirk Hogan, Charles W. Hogue, Christopher G. Hughes, Eric Jacobsohn, Roger A. Johns, Dean R. Jones, Max Kelz, Evan D. Kharasch, Ellen W. King, W. Andrew Kofke, Tom C. Krejcie, Richard M. Langford, H. T. Lee, Isobel Lever, Jerrold H. Levy, J. Lance Lichtor, Larry Lindenbaum, Hung Pin Liu, Geoff Lockwood, Alex Macario, Conan MacDougall, M. B. MacIver, Aman Mahajan, Nándor Marczin, J. A. Jeevendra Martyn, George A. Mashour, Mervyn Maze, Thomas McDowell, Stuart McGrane, Berend Mets, Patrick Meybohm, Charles F. Minto, Jonathan Moss, Mohamed Naguib, Istvan Nagy, Nick Oliver, Paul S. Pagel, Pratik P. Pandharipande, Piyush Patel, Andrew J. Patterson, Robert A. Pearce, Ronald G. Pearl, Misha Perouansky, Kristof Racz, Chinniampalayam Rajamohan, Nilesh Randive, Imre Redai, Stephen Robinson, Richard W. Rosenquist, Carl E. Rosow, Uwe Rudolph, Francis V. Salinas, Robert D. Sanders, Sunita Sastry, Michael Schäfer, Jens Scholz, Thomas W. Schnider, Mark A. Schumacher, John W. Sear, Frédérique S. Servin, Jeffrey H. Silverstein, Tom De Smet, Martin Smith, Joe Henry Steinbach, Markus Steinfath, David F. Stowe, Gary R. Strichartz, Michel M. R. F. Struys, Isao Tsuneyoshi, Robert A. Veselis, Arthur Wallace, Robert P. Walt, David C. Warltier, Nigel R. Webster, Jeanine Wiener-Kronish, Troy Wildes, Paul Wischmeyer, Ling-Gang Wu, Stephen Yang
- Edited by Alex S. Evers, Washington University School of Medicine, St Louis, Mervyn Maze, University of California, San Francisco, Evan D. Kharasch, Washington University School of Medicine, St Louis
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- Book:
- Anesthetic Pharmacology
- Published online:
- 11 April 2011
- Print publication:
- 10 March 2011, pp viii-xiv
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The science of EChO
- Giovanna Tinetti, James Y-K. Cho, Caitlin A. Griffith, Olivier Grasset, Lee Grenfell, Tristan Guillot, Tommi T. Koskinen, Julianne I. Moses, David Pinfield, Jonathan Tennyson, Marcell Tessenyi, Robin Wordsworth, Alan Aylward, Roy van Boekel, Angioletta Coradini, Therese Encrenaz, Ignas Snellen, Maria R. Zapatero-Osorio, Jeroen Bouwman, Vincent Coudé du Foresto, Mercedes Lopez-Morales, Ingo Mueller-Wodarg, Enric Pallé, Franck Selsis, Alessandro Sozzetti, Jean-Philippe Beaulieu, Thomas Henning, Michael Meyer, Giuseppina Micela, Ignasi Ribas, Daphne Stam, Mark Swain, Oliver Krause, Marc Ollivier, Emanuele Pace, Bruce Swinyard, Peter A.R. Ade, Nick Achilleos, Alberto Adriani, Craig B. Agnor, Cristina Afonso, Carlos Allende Prieto, Gaspar Bakos, Robert J. Barber, Michael Barlow, Peter Bernath, Bruno Bézard, Pascal Bordé, Linda R. Brown, Arnaud Cassan, Céline Cavarroc, Angela Ciaravella, Charles Cockell, Athéna Coustenis, Camilla Danielski, Leen Decin, Remco De Kok, Olivier Demangeon, Pieter Deroo, Peter Doel, Pierre Drossart, Leigh N. Fletcher, Matteo Focardi, Francois Forget, Steve Fossey, Pascal Fouqué, James Frith, Marina Galand, Patrick Gaulme, Jonay I. González Hernández, Davide Grassi, Matt J. Griffin, Ulrich Grözinger, Manuel Guedel, Pactrick Guio, Olivier Hainaut, Robert Hargreaves, Peter H. Hauschildt, Kevin Heng, David Heyrovsky, Ricardo Hueso, Pat Irwin, Lisa Kaltenegger, Patrick Kervella, David Kipping, Geza Kovacs, Antonino La Barbera, Helmut Lammer, Emmanuel Lellouch, Giuseppe Leto, Mercedes Lopez Morales, Miguel A. Lopez Valverde, Manuel Lopez-Puertas, Christophe Lovi, Antonio Maggio, Jean-Pierre Maillard, Jesus Maldonado Prado, Jean-Baptiste Marquette, Francisco J. Martin-Torres, Pierre Maxted, Steve Miller, Sergio Molinari, David Montes, Amaya Moro-Martin, Olivier Mousis, Napoléon Nguyen Tuong, Richard Nelson, Glenn S. Orton, Eric Pantin, Enzo Pascale, Stefano Pezzuto, Ennio Poretti, Raman Prinja, Loredana Prisinzano, Jean-Michel Réess, Ansgar Reiners, Benjamin Samuel, Jorge Sanz Forcada, Dimitar Sasselov, Giorgio Savini, Bruno Sicardy, Alan Smith, Lars Stixrude, Giovanni Strazzulla, Gautam Vasisht, Sandrine Vinatier, Serena Viti, Ingo Waldmann, Glenn J. White, Thomas Widemann, Roger Yelle, Yuk Yung, Sergey Yurchenko
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- Journal:
- Proceedings of the International Astronomical Union / Volume 6 / Issue S276 / October 2010
- Published online by Cambridge University Press:
- 10 November 2011, pp. 359-370
- Print publication:
- October 2010
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The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are?
In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life.
The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole.
EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates.
On the (S – 1, S) Stock Model for Renewal Demand Processes: Poisson's poison
- Marcel A. J. Smith, Rommert Dekker
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- Journal:
- Probability in the Engineering and Informational Sciences / Volume 11 / Issue 3 / July 1997
- Published online by Cambridge University Press:
- 27 July 2009, pp. 375-386
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In the standard (S – 1, S) stock model, demand follows a Poisson process. It has appeared to many stock analysts that this model causes an abundance of stock in reality. In case demand is caused by failure or is derived from another process, demand typically does not follow a Poisson process. In this paper, we discuss the (S – 1, S) stock model where demand follows a renewal process and the lead time is deterministic. Moreover, we will extend this to compound renewal demand and multi-echelon inventory systems. Our goal is to show the severe influence of taking the Poisson process for granted.
An Approximation of the Interval Availability Distribution
- Marcel A. J. Smith
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- Journal:
- Probability in the Engineering and Informational Sciences / Volume 11 / Issue 4 / October 1997
- Published online by Cambridge University Press:
- 27 July 2009, pp. 451-467
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In this paper, we consider the interval availability distribution of a two-state single unit. We fit the interval availability distribution directly to a beta distribution, such that the probability of nil and a 100% availability is correct as well as the expectation and the variance. The method is fast and easy to implement and gives good results.