89 results on '"Pierre Lepage"'
Search Results
2. WEGS: a cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome
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Claude Bhérer, Robert Eveleigh, Katerina Trajanoska, Janick St-Cyr, Antoine Paccard, Praveen Nadukkalam Ravindran, Elizabeth Caron, Nimara Bader Asbah, Clare Wei, Iris Baumgartner, Marc Schindewolf, Yvonne Döring, Danielle Perley, François Lefebvre, Pierre Lepage, Mathieu Bourgey, Guillaume Bourque, Jiannis Ragoussis, Vincent Mooser, and Daniel Taliun
- Abstract
0AbstractWhole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a novel, cost-effective method, which we call “Whole Exome Genome Sequencing” (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.
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- 2023
3. Do age of consent laws decrease teen births?
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Louis‐Pierre Lepage
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Economics and Econometrics - Published
- 2022
4. Strategies to improve access to physical activity opportunities for people with physical disabilities
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Jordan D Herbison, Meaghan Osborne, Jessica Andersen, Pierre Lepage, Véronique Pagé, Caroline Levasseur, Mélissa Beckers, Heather L Gainforth, Marie-Eve Lamontagne, and Shane N Sweet
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Behavioral Neuroscience ,Applied Psychology - Abstract
Community-based physical activity opportunities have been shown to help adults with physical disabilities improve their participation in daily activities and reduce social isolation. Despite the known benefits, substantial barriers and challenges inhibit accessibility to these physical activity opportunities. To facilitate the co-construction of strategies to overcome accessibility issues pertaining to community-based physical activity opportunities. In total, 45 individuals with physical disabilities, patients at a rehabilitation hospital, staff members of disability organizations, staff of local or provincial government agencies/departments, kinesiologists, occupational therapists, graduate students, and peer mentors participated in one of four World Cafés held in their respective cities. World Café is a methodology for fostering collaborative, solution-focused conversation that aims to solve problems through collective intelligence. Participants were divided into groups of three to four people and invited to engage in evolving rounds of discussions responding to prompts about accessibility to physical activity in their communities. Transcripts were analyzed using content analysis. In total, 17 strategies were identified, addressing 5 areas: representation and visibility (e.g., prioritize hiring people with a disability), finances (e.g., reduce direct costs for participants), connection and social support (e.g., foster social networks that provide informational support), education and programming (e.g., enhance awareness of existing services and resources), and government programs and policies (e.g., enforce accessibility standards for indoor and outdoor spaces). The findings of this study provide strategies and practical applications for community programs and governments to consider for increasing access to physical activity opportunities for people with physical disabilities.
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- 2023
5. Anticipated Gender Discrimination and Grade Disclosure
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Louis-Pierre Lepage, Xiaomeng Li, and Basit Zafar
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- 2022
6. Validation au Québec d’équations pour prédire la valeur nutritive de la luzerne au champ avant la récolte
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Shane Wood, Sandrine St-Pierre-Lepage, Gilles Bélanger, Gaëtan F. Tremblay, Huguette Martel, Philippe Seguin, Julie Lajeunesse, and Annie Claessens
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0106 biological sciences ,Neutral Detergent Fiber ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Forestry ,04 agricultural and veterinary sciences ,Plant Science ,Horticulture ,01 natural sciences ,Agronomy and Crop Science ,010606 plant biology & botany ,Mathematics - Abstract
Des équations précédemment développées prédisent la valeur nutritive de la luzerne ou de mélanges luzerne–graminée avant la récolte. Cette étude valide cinq de ces équations avec des échantillons de luzerne pure cultivée sous conditions québécoises. Ces équations de prédiction ont été évaluées en utilisant les statistiques associées aux régressions linéaires. Parmi les équations évaluées, celle du Wisconsin et de New York semblaient les plus appropriées. Cependant, la présence de biais limite leur utilisation. Le développement d’une équation québécoise devrait donc être considéré afin d’aider les producteurs à identifier le moment de récolte de toutes les cultures à base de luzerne.
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- 2021
7. Discrimination and sorting in the real estate market: Evidence from terrorist attacks and mosques
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Louis-Pierre Lepage
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Economics and Econometrics ,Finance - Published
- 2023
8. Productivity and persistence of Kura clover and white clover mixtures with grasses
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Sandrine St-Pierre-Lepage, Florence Pomerleau-Lacasse, Raynald Drapeau, Philippe Seguin, and Julie Lajeunesse
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0106 biological sciences ,White (horse) ,Agronomy ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,04 agricultural and veterinary sciences ,Biology ,01 natural sciences ,Agronomy and Crop Science ,Productivity ,010606 plant biology & botany ,Persistence (computer science) - Published
- 2020
9. Anticipated Gender Discrimination and Grade Disclosure
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Louis Pierre Lepage, Xiaomeng Li, and Basit Zafar
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
10. Learning to Discriminate on the Job
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Alan Benson and Louis Pierre Lepage
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
11. Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19
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Mohamed Fawzy, David Goldstein, Mansour S Almutairi, Nora Aljawini, Naveed Aziz, Serghei Mangul, Krzysztof Kiryluk, J. Brent Richards, Sirui Zhou, Hani M. Al-Afghani, Vincent Mooser, Bartha Maria Knoppers, May Alrashed, Nour Albes, Saleh A. Alqahtani, Radja Badji, Lisa J. Strug, Atlas Khan, Manal Alaamery, Yaseen M. Arabi, Mathieu Bourgey, Leen Abu-Safieh, Vincenzo Forgetta, Guillaume Bourque, Bader Alghamdi, Steven J.M. Jones, Chadi Saad, Salam Massadeh, Guillaume Butler-Laporte, Jiannis Ragoussis, Abdulraheem Alshareef, Wadha Al-Muftah, Gundula Povysil, Chen Wang, Stephen W. Scherer, Robert Eveleigh, Ebrahim Mahmoud, Said I. Ismail, Pierre Lepage, Hamdi Mbarek, Abdulaziz Almalik, Mark Lathrop, Tomoko Nakanishi, Bandar A. Suliman, Junghyun Jung, Ali G. Gharavi, Jahad Alghamdi, Ning Shang, Malak Abedalthagafi, Hadeel El Bardisy, Asma Al Thani, and Fawz S. Al Harthi
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0301 basic medicine ,Candidate gene ,education.field_of_study ,Mutation ,Population ,Case-control study ,macromolecular substances ,General Medicine ,Biology ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Genetic variation ,Immunology ,medicine ,education ,Gene ,Loss function ,Exome sequencing - Abstract
A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.
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- 2021
12. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
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Matteo D’Antonio, Jennifer P. Nguyen, Timothy D. Arthur, Hiroko Matsui, Agnieszka D’Antonio-Chronowska, Kelly A. Frazer, Benjamin M. Neale, Mark Daly, Andrea Ganna, Christine Stevens, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Mattia Cordioli, Juha Karjalainen, Renato Polimanti, Matti Pirinen, Nadia Harerimana, Kumar Veerapen, Brooke Wolford, Huy Nguyen, Matthew Solomonson, Rachel G. Liao, Karolina Chwialkowska, Amy Trankiem, Mary K. Balaconis, Caroline Hayward, Anne Richmond, Archie Campbell, Marcela Morris, Chloe Fawns-Ritchie, Joseph T. Glessner, Douglas M. Shaw, Xiao Chang, Hannah Polikowski, Petty E. Lauren, Hung-Hsin Chen, Zhu Wanying, Hakon Hakonarson, David J. Porteous, Jennifer Below, Kari North, Joseph B. McCormick, Paul R.H.J. Timmers, James F. Wilson, Albert Tenesa, Kenton D’Mellow, Shona M. Kerr, Mari E.K. Niemi, Lindokuhle Nkambul, Kathrin Aprile von Hohenstaufen, Ali Sobh, Madonna M. Eltoukhy, Amr M. Yassen, Mohamed A.F. Hegazy, Kamal Okasha, Mohammed A. Eid, Hanteera S. Moahmed, Doaa Shahin, Yasser M. El-Sherbiny, Tamer A. Elhadidy, Mohamed S. Abd Elghafar, Jehan J. El-Jawhari, Attia A.S. Mohamed, Marwa H. Elnagdy, Amr Samir, Mahmoud Abdel-Aziz, Walid T. Khafaga, Walaa M. El-Lawaty, Mohamed S. Torky, Mohamed R. El-shanshory, Chiara Batini, Paul H. Lee, Nick Shrine, Alexander T. Williams, Martin D. Tobin, Anna L. Guyatt, Catherine John, Richard J. Packer, Altaf Ali, Robert C. Free, Xueyang Wang, Louise V. Wain, Edward J. Hollox, Laura D. Venn, Catherine E. Bee, Emma L. Adams, Ahmadreza Niavarani, Bahareh Sharififard, Rasoul Aliannejad, Ali Amirsavadkouhi, Zeinab Naderpour, Hengameh Ansari Tadi, Afshar Etemadi Aleagha, Saeideh Ahmadi, Seyed Behrooz Mohseni Moghaddam, Alireza Adamsara, Morteza Saeedi, Hamed Abdollahi, Abdolmajid Hosseini, Pajaree Chariyavilaskul, Monpat Chamnanphon, Thitima B. Suttichet, Vorasuk Shotelersuk, Monnat Pongpanich, Chureerat Phokaew, Wanna Chetruengchai, Watsamon Jantarabenjakul, Opass Putchareon, Pattama Torvorapanit, Thanyawee Puthanakit, Pintip Suchartlikitwong, Nattiya Hirankarn, Voraphoj Nilaratanakul, Pimpayao Sodsai, Ben M. Brumpton, Kristian Hveem, Cristen Willer, Wei Zhou, Tormod Rogne, Erik Solligard, Bjørn Olav Åsvold, Malak Abedalthagafi, Manal Alaamery, Saleh Alqahtani, Dona Baraka, Fawz Al Harthi, Ebtehal Alsolm, Leen Abu Safieh, Albandary M. Alowayn, Fatimah Alqubaishi, Amal Al Mutairi, Serghei Mangul, Abdulraheem Alshareef, Mona Sawaji, Mansour Almutairi, Nora Aljawini, Nour Albesher, Yaseen M. Arabi, Ebrahim S. Mahmoud, Amin K. Khattab, Roaa T. Halawani, Ziab Z. Alahmadey, Jehad K. Albakri, Walaa A. Felemban, Bandar A. Suliman, Rana Hasanato, Laila Al-Awdah, Jahad Alghamdi, Deema AlZahrani, Sameera AlJohani, Hani Al-Afghani, May Alrashed, Nouf AlDhawi, Hadeel AlBardis, Sarah Alkwai, Moneera Alswailm, Faisal Almalki, Maha Albeladi, Iman Almohammed, Eman Barhoush, Anoud Albader, Salam Massadeh, Abdulaziz AlMalik, Sara Alotaibi, Bader Alghamdi, Junghyun Jung, Mohammad S. Fawzy, Yunsung Lee, Per Magnus, Lill-Iren S. Trogstad, Øyvind Helgeland, Jennifer R. Harris, Massimo Mangino, Tim D. Spector, Duncan Emma, Sandra P. Smieszek, Bartlomiej P. Przychodzen, Christos Polymeropoulos, Vasilios Polymeropoulos, Mihael H. Polymeropoulos, Israel Fernandez-Cadenas, Jordi Perez-Tur, Laia Llucià-Carol, Natalia Cullell, Elena Muiño, Jara Cárcel-Márquez, Marta L. DeDiego, Lara Lloret Iglesias, Anna M. Planas, Alex Soriano, Veronica Rico, Daiana Agüero, Josep L. Bedini, Francisco Lozano, Carlos Domingo, Veronica Robles, Francisca Ruiz-Jaén, Leonardo Márquez, Juan Gomez, Eliecer Coto, Guillermo M. Albaiceta, Marta García-Clemente, David Dalmau, Maria J. Arranz, Beatriz Dietl, Alex Serra-Llovich, Pere Soler, Roger Colobrán, Andrea Martín-Nalda, Alba Parra Martínez, David Bernardo, Silvia Rojo, Aida Fiz-López, Elisa Arribas, Paloma de la Cal-Sabater, Tomás Segura, Esther González-Villa, Gemma Serrano-Heras, Joan Martí-Fàbregas, Elena Jiménez-Xarrié, Alicia de Felipe Mimbrera, Jaime Masjuan, Sebastian García-Madrona, Anna Domínguez-Mayoral, Joan Montaner Villalonga, Paloma Menéndez-Valladares, Daniel I. Chasman, Julie E. Buring, Paul M. Ridker, Giulianini Franco, Howard D. Sesso, JoAnn E. Manson, Joseph R. Glessner, Carolina Medina-Gomez, Andre G. Uitterlinden, M. Arfan Ikram, Kati Kristiansson, Sami Koskelainen, Markus Perola, Kati Donner, Katja Kivinen, Aarno Palotie, Samuli Ripatti, Sanni Ruotsalainen, Mari Kaunisto, null FinnGen, Tomoko Nakanishi, Guillaume Butler-Laporte, Vincenzo Forgetta, David R. Morrison, Biswarup Ghosh, Laetitia Laurent, Alexandre Belisle, Danielle Henry, Tala Abdullah, Olumide Adeleye, Noor Mamlouk, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk Branka Vulesevic, Meriem Bouab, Charlotte Guzman, Louis Petitjean, Chris Tselios, Xiaoqing Xue, Erwin Schurr, Jonathan Afilalo, Marc Afilalo, Maureen Oliveira, Bluma Brenner, Pierre Lepage, Jiannis Ragoussis, Daniel Auld, Nathalie Brassard, Madeleine Durand, Michaël Chassé, Daniel E. Kaufmann, G. Mark Lathrop, Vincent Mooser, J. Brent Richards, Rui Li, Darin Adra, Souad Rahmouni, Michel Georges, Michel Moutschen, Benoit Misset, Gilles Darcis, Julien Guiot, Julien Guntz, Samira Azarzar, Stéphanie Gofflot, Yves Beguin, Sabine Claassen, Olivier Malaise, Pascale Huynen, Christelle Meuris, Marie Thys, Jessica Jacques, Philippe Léonard, Frederic Frippiat, Jean-Baptiste Giot, Anne-Sophie Sauvage, Christian Von Frenckell, Yasmine Belhaj, Bernard Lambermont, Sara Pigazzini, Lindokuhle Nkambule, Michelle Daya, Jonathan Shortt, Nicholas Rafaels, Stephen J. Wicks, Kristy Crooks, Kathleen C. Barnes, Christopher R. Gignoux, Sameer Chavan, Triin Laisk, Kristi Läll, Maarja Lepamets, Reedik Mägi, Tõnu Esko, Ene Reimann, Lili Milani, Helene Alavere, Kristjan Metsalu, Mairo Puusepp, Andres Metspalu, Paul Naaber, Edward Laane, Jaana Pesukova, Pärt Peterson, Kai Kisand, Jekaterina Tabri, Raili Allos, Kati Hensen, Joel Starkopf, Inge Ringmets, Anu Tamm, Anne Kallaste, Pierre-Yves Bochud, Carlo Rivolta, Stéphanie Bibert, Mathieu Quinodoz, Dhryata Kamdar, Noémie Boillat, Semira Gonseth Nussle, Werner Albrich, Noémie Suh, Dionysios Neofytos, Véronique Erard, Cathy Voide, null FHoGID, null RegCOVID, null P-PredictUs, null SeroCOVID, null CRiPSI, Rafael de Cid, Iván Galván-Femenía, Natalia Blay, Anna Carreras, Beatriz Cortés, Xavier Farré, Lauro Sumoy, Victor Moreno, Josep Maria Mercader, Marta Guindo-Martinez, David Torrents, Manolis Kogevinas, Judith Garcia-Aymerich, Gemma Castaño-Vinyals, Carlota Dobaño, Alessandra Renieri, Francesca Mari, Chiara Fallerini, Sergio Daga, Elisa Benetti, Margherita Baldassarri, Francesca Fava, Elisa Frullanti, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Rossella Tita, Sara Amitrano, Mirella Bruttini, Susanna Croci, Ilaria Meloni, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Giada Beligni, Andrea Tommasi, Laura Di Sarno, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Stefano Busani, Raffaele Bruno, Marco Vecchia, Mary Ann Belli, Nicola Picchiotti, Maurizio Sanarico, Marco Gori, Simone Furini, Stefania Mantovani, Serena Ludovisi, Mario Umberto Mondelli, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Massimo Vaghi, Stefano Rusconi, Matteo Siano, Francesca Montagnani, Arianna Emiliozzi, Massimiliano Fabbiani, Barbara Rossetti, Elena Bargagli, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Maria Bandini, Gian Piero Caldarelli, Paolo Piacentini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Massimo Girardis, Sophie Venturelli, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Stefano Baratti, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Carmen Marciano, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Serafina Valente, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Sandro Mancarella, Luisa Tavecchia, Lia Crotti, Chiara Gabbi, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Stefano Ceri, Pietro Pinoli, Francesco Raimondi, Filippo Biscarini, Alessandra Stella, Kristina Zguro, Katia Capitani, Claudia Suardi, Simona Dei, Gianfranco Parati, Sabrina Ravaglia, Rosangela Artuso, Giordano Bottà, Paolo Di Domenico, Ilaria Rancan, Antonio Perrella Francesco Bianchi, Davide Romani, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Marco Tanfoni, Antonella Vincenti, Claudio Ferri, Davide Grassi, Gloria Pessina, Mario Tumbarello, Massimo Di Pietro, Ravaglia Sabrina, Sauro Luchi, Chiara Barbieri, Donatella Acquilini, Elena Andreucci, Francesco Vladimiro Segala, Giusy Tiseo, Marco Falcone, Mirjam Lista, Monica Poscente, Oreste De Vivo, Paola Petrocelli, Alessandra Guarnaccia, Silvia Baroni, Albert V. Smith, Andrew P. Boughton, Kevin W. Li, Jonathon LeFaive, Aubrey Annis, Anne E. Justice, Tooraj Mirshahi, Geetha Chittoor, Navya Shilpa Josyula, Jack A. Kosmicki, Manuel A.R. Ferreira, Joseph B. Leader, Dave J. Carey, Matthew C. Gass, Julie E. Horowitz, Michael N. Cantor, Ashish Yadav, Aris Baras, Goncalo R. Abecasis, David A. van Heel, Karen A. Hunt, Dan Mason, Qin Qin Huang, Sarah Finer, null Genes & Health Research Team, Bhavi Trivedi, Christopher J. Griffiths, Hilary C. Martin, John Wright, Richard C. Trembath, Nicole Soranzo, Jing Hua Zhao, Adam S. Butterworth, John Danesh, Emanuele Di Angelantonio, Lude Franke Marike Boezen, Patrick Deelen, Annique Claringbould, Esteban Lopera, Robert Warmerdam, Judith.M. Vonk, Irene van Blokland, Pauline Lanting, Anil P.S. Ori, Brooke Wolford Sebastian Zöllner, Jiongming Wang, Andrew Beck, Gina Peloso, Yuk-Lam Ho, Yan V. Sun, Jennifer E. Huffman, Christopher J. O’Donnell, Kelly Cho, Phil Tsao, J. Michael Gaziano, Michel (M.G.) Nivard, Eco (E.J.C.) de geus, Meike Bartels, Jouke Jan Hottenga, Scott T. Weiss, Elizabeth W. Karlson, Jordan W. Smoller, Robert C. Green, Yen-Chen Anne Feng, Josep Mercader, Shawn N. Murphy, James B. Meigs, Ann E. Woolley, Emma F. Perez, Daniel Rader, Anurag Verma, Marylyn D. Ritchie, Binglan Li, Shefali S. Verma, Anastasia Lucas, Yuki Bradford, Hugo Zeberg, Robert Frithiof, Michael Hultström, Miklos Lipcsey, Lindo Nkambul, Nicolas Tardif, Olav Rooyackers, Jonathan Grip, Tomislav Maricic, Konrad J. Karczewski, Elizabeth G. Atkinson, Kristin Tsuo, Nikolas Baya, Patrick Turley, Rahul Gupta, Shawneequa Callier, Raymond K. Walters, Duncan S. Palmer, Gopal Sarma, Nathan Cheng, Wenhan Lu, Sam Bryant, Claire Churchhouse, Caroline Cusick, Jacqueline I. Goldstein, Daniel King, Cotton Seed, Hilary Finucane, Alicia R. Martin, F. Kyle Satterstrom, Daniel J. Wilson, Jacob Armstrong, Justine K. Rudkin, Gavin Band, Sarah G. Earle, Shang-Kuan Lin, Nicolas Arning, Derrick W. Crook, David H. Wyllie, Anne Marie O’Connell, Chris C.A. Spencer, Nils Koelling, Mark J. Caulfield, Richard H. Scott, Tom Fowler, Loukas Moutsianas, Athanasios Kousathanas, Dorota Pasko, Susan Walker, Augusto Rendon, Alex Stuckey, Christopher A. Odhams, Daniel Rhodes, Georgia Chan, Prabhu Arumugam, Catherine A. Ball, Eurie L. Hong, Kristin Rand, Ahna Girshick, Harendra Guturu, Asher Haug Baltzell, Genevieve Roberts, Danny Park, Marie Coignet, Shannon McCurdy, Spencer Knight, Raghavendran Partha, Brooke Rhead, Miao Zhang, Nathan Berkowitz, Michael Gaddis, Keith Noto, Luong Ruiz, Milos Pavlovic, Laura G. Sloofman, Alexander W. Charney, Noam D. Beckmann, Eric E. Schadt, Daniel M. Jordan, Ryan C. Thompson, Kyle Gettler, Noura S. Abul-Husn, Steven Ascolillo, Joseph D. Buxbaum, Kumardeep Chaudhary, Judy H. Cho, Yuval Itan, Eimear E. Kenny, Gillian M. Belbin, Stuart C. Sealfon, Robert P. Sebra, Irene Salib, Brett L. Collins, Tess Levy, Bari Britvan, Katherine Keller, Lara Tang, Michael Peruggia, Liam L. Hiester, Kristi Niblo, Alexandra Aksentijevich, Alexander Labkowsky, Avromie Karp, Menachem Zlatopolsky, Michael Preuss, Ruth J.F. Loos, Girish N. Nadkarni, Ron Do, Clive Hoggart, Sam Choi, Slayton J. Underwood, Paul O’Reilly, Laura M. Huckins, Marissa Zyndorf, AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology
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Medical Physiology ,Gene Expression ,Genome-wide association study ,Genome ,Severity of Illness Index ,colocalization ,Gene expression ,Databases, Genetic ,Ethnicity ,2.1 Biological and endogenous factors ,GWAS ,Aetiology ,Biology (General) ,Lung ,Genetics ,Chromosome Mapping ,Single Nucleotide ,Organ Specificity ,Biotechnology ,Cell type ,QH301-705.5 ,Quantitative Trait Loci ,Single-nucleotide polymorphism ,Biology ,eQTL ,Polymorphism, Single Nucleotide ,Article ,General Biochemistry, Genetics and Molecular Biology ,Databases ,Genetic ,SNP ,Humans ,Genetic Predisposition to Disease ,COVID-19 Host Genetics Initiative ,Polymorphism ,Gene ,COVID-19 ,SARS-CoV-2 ,Gene Expression Profiling ,Prevention ,Human Genome ,Computational Biology ,Genetic Variation ,Good Health and Well Being ,Expression quantitative trait loci ,Biochemistry and Cell Biology ,Transcriptome ,Genome-Wide Association Study - Abstract
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.
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- 2022
13. Lésions médullaires et activités physiques adaptées
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Pierre Lepage, Caroline Levasseur, Emilie Michalovic, Véronique Pagé, and Shane N Sweet
- Published
- 2020
14. Endogenous Learning, Persistent Employer Biases, and Discrimination
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Louis Pierre Lepage
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History ,Polymers and Plastics ,business.industry ,media_common.quotation_subject ,Wage ,Contrast (statistics) ,Distribution (economics) ,Industrial and Manufacturing Engineering ,Incentive ,Investment decisions ,Economics ,Demographic economics ,Business and International Management ,business ,Productivity ,Statistical discrimination ,health care economics and organizations ,Prejudice (legal term) ,media_common - Abstract
I present a statistical discrimination model of the labor market in which employers are initially uncertain about the productivity of worker groups and endogenously learn about it through their hiring. Previous hiring experiences with groups shape subsequent incentives of employers to hire from these groups again and learn more about their productivity, leading to differential learning across employers and biased beliefs about the productivity of groups. Given a market-clearing wage, optimal hiring follows a cutoff rule in posterior beliefs: employers with sufficiently negative experiences with workers from a group stop hiring from the group, preserving negative biases and leading to a negatively-skewed distribution of beliefs about their productivity. When employers have noisier initial information on the productivity of one worker group, discrimination against the group can arise and persist without productivity differentials or prior employer biases, with market competition, and with or without worker signaling or investment decisions. The model generates steady state predictions analogous to the Becker (1957) taste-based model, in a statistical framework with beliefs replacing preferences, explaining apparent prejudice as the result of "incorrect" statistical discrimination. The model also generates additional predictions with policy implications that contrast with traditional models of discrimination.
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- 2020
15. How Do NYPD Officers Respond to Terror Threats?
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Steven Lehrer and Louis Pierre Lepage
- Published
- 2019
16. Sternohyoid muscles for reconstruction after thyroid cartilage anterior partial resection
- Author
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Jerôme Keghian, Marc Remacle, Florence Rogister, Pierre Lepage, and Anna Pamela Dela Cruz
- Subjects
medicine.medical_specialty ,Sternum ,business.industry ,medicine.medical_treatment ,Hyoid bone ,Thyroidectomy ,Anatomy ,Partial resection ,Thyroid cartilage ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,medicine ,030223 otorhinolaryngology ,business - Published
- 2017
17. Does Selective Crime Reporting Influence Our Ability to Detect Racial Discrimination in the Nypd’s Stop-and-Frisk Program?
- Author
-
Louis-Pierre Lepage and Steven F. Lehrer
- Subjects
Officer ,Sample selection ,Crime type ,media_common.quotation_subject ,Racial bias ,Criminology ,Psychology ,Racism ,Selection (genetic algorithm) ,Crime reporting ,media_common - Abstract
Prior analyses of racial bias in the New York City’s Stop-and-Frisk program implicitly assumed that potential bias of police officers did not vary by crime type and that their decision of which type of crime to report as the basis for the stop did not exhibit any bias. In this paper, we first extend the hit rates model to consider crime type heterogeneity in racial bias and police officer decisions of reported crime type. Second, we reevaluate the program while accounting for heterogeneity in bias along crime types and for the sample selection which may arise from conditioning on crime type. We present evidence that differences in biases across crime types are substantial and specification tests support incorporating corrections for selective crime reporting. However, the main findings on racial bias do not differ sharply once accounting for this choice-based selection.
- Published
- 2019
18. Development and Acquisition of Knowledge of Youth Parasport Coaches
- Author
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Pierre Lepage, William R. Falcão, and Gordon A. Bloom
- Subjects
Male ,030506 rehabilitation ,Physical Education and Training ,Adolescent ,Interpretation (philosophy) ,Applied psychology ,Mentors ,Mentoring ,Physical Therapy, Sports Therapy and Rehabilitation ,030229 sport sciences ,03 medical and health sciences ,A physical disability ,0302 clinical medicine ,Learning opportunities ,Humans ,Learning ,Disabled Persons ,Use of technology ,Thematic analysis ,0305 other medical science ,Psychology ,Qualitative Research ,Meaning (linguistics) ,Sports - Abstract
The purpose of this study was to understand the learning experiences and acquisition of knowledge of youth parasport coaches. Five able-bodied male participants (M = 39 years old), who coached youth with a physical disability for an average of 7.4 years, participated in individual interviews. An inductive thematic analysis identified patterns within and across the data, allowing for description and interpretation of the meaning and importance of the themes. The results showed that coaches learned mostly from informal experiences, particularly through mentoring, trial and error, or use of technology. In addition, these learning opportunities were influenced by personal, environmental, and social factors. These findings can help to guide current and future generations of coaches of youth participants with a physical disability by highlighting available resources and addressing several barriers and facilitators to their learning.
- Published
- 2019
19. Are criminals strategic? Offender responses to drug sentencing cutoffs
- Author
-
Louis-Pierre Lepage
- Subjects
Organizational Behavior and Human Resource Management ,Economics and Econometrics ,Labour economics ,Punishment ,media_common.quotation_subject ,05 social sciences ,Criminology ,Incentive ,Margin (machine learning) ,Irrational number ,0502 economics and business ,Economics ,Cutoff ,Deterrence (legal) ,050207 economics ,050205 econometrics ,media_common ,Criminal justice - Abstract
In many US states, punishment severity for drug offenses increases discontinuously at established quantity limits. Theory predicts that these laws create bunching of offenders at these limits and dominated regions beyond, where it ex-ante appears irrational to locate. These policies provide a novel setting to test for deterrence along a different margin that typically considered in the literature and generate new evidence on the extent to which offenders respond to incentives. Using arrest reports from 28 states and leveraging variation from quantity cutoff changes through time, I find evidence of strategic bunching by offenders in response to cutoff policies.
- Published
- 2020
20. Protists Within Corals: The Hidden Diversity
- Author
-
Eve Toulza, Jeremie Vidal-Dupiol, Mehdi Adjeroud, Laure Guillou, Pierre Lepage, Jean-Michel Escoubas, Camille Clerissi, Sébastien Brunet, Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), Adaptation et diversité en milieu marin (AD2M), Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), McGill University and Genome Quebec Innovation Centre, Diversité et Interactions au sein du Plancton Océanique (DIPO), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Station biologique de Roscoff (SBR), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0106 biological sciences ,0301 basic medicine ,Microbiology (medical) ,Coral ,lcsh:QR1-502 ,Scleractinia ,Pocillopora damicornis ,medicine.disease_cause ,01 natural sciences ,Microbiology ,lcsh:Microbiology ,Montastraea ,03 medical and health sciences ,Symbiodinium ,parasitic diseases ,medicine ,14. Life underwater ,holobiont ,Favia ,protists ,geography ,blocking primer ,geography.geographical_feature_category ,biology ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,010604 marine biology & hydrobiology ,fungi ,Protist ,Coral reef ,biology.organism_classification ,symbiosis ,030104 developmental biology ,Evolutionary biology ,metabarcoding - Abstract
International audience; Previous observations suggested that microbial communities contribute to coral health and the ecological resilience of coral reefs. However, most studies of coral microbiology focused on prokaryotes and the endosymbiotic algae Symbiodinium. In contrast, knowledge concerning diversity of other protists is still lacking, possibly due to methodological constraints. As most eukaryotic DNA in coral samples was derived from hosts, protist diversity was missed in metagenome analyses. To tackle this issue, we designed blocking primers for Scleractinia sequences amplified with two primer sets that targeted variable loops of the 18S rRNA gene (18SV1V2 and 18SV4). These blocking primers were used on environmental colonies of Pocillopora damicornis sensu lato from two regions with contrasting thermal regimes (Djibouti and New Caledonia). In addition to Symbiodinium clades A/C/D, Licnophora and unidentified coccidia genera were found in many samples. In particular, coccidian sequences formed a robust monophyletic clade with other protists identified in Agaricia, Favia, Montastraea, Mycetophyllia, Porites, and Siderastrea coral colonies. Moreover, Licnophora and coccidians had different distributions between the two geographic regions. A similar pattern was observed between Symbiodinium clades C and A/D. Although we were unable to identify factors responsible for this pattern, nor were we able to confirm that these taxa were closely associated with corals, we believe that these primer sets and the associated blocking primers offer new possibilities to describe the hidden diversity of protists within different coral species.
- Published
- 2018
21. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age
- Author
-
László Bognár, Sébastien Brunet, David T.W. Jones, Andrey Korshunov, Geneviève Bourret, Denise Bechet, Dong-Anh Khuong-Quang, Jose-Luis Montes, Nicolas De Jay, Noha Gerges, Pierre Lepage, Huriye Seker-Cin, Tenzin Gayden, Tony Kwan, V. Peter Collins, Uri Tabori, Margret Shirinian, Werner Paulus, M Kool, Stefan M. Pfister, Adam M. Fontebasso, Hendrik Witt, Karine Jacob, Barbara Hutter, Jean-Pierre Farmer, Peter Hauser, Almos Klekner, Damien Faury, Jeffrey Atkinson, Nada Jabado, Steffen Albrecht, Alexandre Montpetit, Sally R. Lambert, Miklós Garami, and Martin Hasselblatt
- Subjects
Adult ,Male ,Proto-Oncogene Proteins B-raf ,Brain tumor ,Aneuploidy ,Astrocytoma ,Real-Time Polymerase Chain Reaction ,Klinikai orvostudományok ,medicine.disease_cause ,BRAF ,Cohort Studies ,Young Adult ,MDM2 ,Biomarkers, Tumor ,medicine ,Humans ,RNA, Messenger ,Receptor, Fibroblast Growth Factor, Type 1 ,aneuploidy ,pilocytic astrocytoma ,Young adult ,Child ,Neoplasm Staging ,Mutation ,biology ,Pilocytic astrocytoma ,Brain Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,aging ,Age Factors ,Proto-Oncogene Proteins c-mdm2 ,Orvostudományok ,Cell cycle ,Prognosis ,medicine.disease ,Oncology ,biology.protein ,Cancer research ,Mdm2 ,Female ,PLK2 ,Research Paper - Abstract
Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.
- Published
- 2015
22. Telehomecare telecommunication framework - from remote patient monitoring to video visits and robot telepresence
- Author
-
Pierre Lepage, Simon Brière, François Michaud, Mathieu Hamel, Michel Tousignant, Hélène Corriveau, and Dominic Létourneau
- Subjects
Service (systems architecture) ,Engineering ,020205 medical informatics ,Remote patient monitoring ,02 engineering and technology ,Telehealth ,computer.software_genre ,03 medical and health sciences ,User-Computer Interface ,0302 clinical medicine ,Videoconferencing ,0202 electrical engineering, electronic engineering, information engineering ,Humans ,030212 general & internal medicine ,Telehomecare ,Monitoring, Physiologic ,Multimedia ,business.industry ,Remote Consultation ,Ranging ,Robotics ,Telemedicine ,Telecommunications ,Robot ,Mobile telephony ,business ,computer ,Wireless Technology - Abstract
Over the last few years, the number of remote patient monitoring (RPM) products and of videoconferencing systems has exploded. There is also a significant number of research initiatives addressing the use of service robots for assistance in daily living activities. From a technological standpoint, providing telehomecare services is certainly feasible. However, one technological barrier is to have access to a telecommunication platform that can be adapted to address the broad range of specifications and requirements of clinical and telehealth applications. Handling the full spectrum of possibilities requires a telecommunication framework that can transmit vital sign data from patients to clinicians, bidirectional audio-video from a standard computing device, and also multiple video streams and bidirectional transmission of control data. This paper presents a framework that integrates such capabilities. It also illustrates the versatility of the framework by presenting custom-designed devices allowing integration of capabilities ranging from RPM to video visits and robot telepresence.
- Published
- 2017
23. Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine
- Author
-
Kathryn Vaillancourt, Gary G. Chen, Jeffrey A. Gross, Ulrike Ehlert, Alexandre Bramoullé, Elena Gardini, Gustavo Turecki, Gilles Maussion, Jean-François Théroux, Aurélie Masurel, Pierre Lepage, Naguib Mechawar, Carl Ernst, Pierre-Eric Lutz, Geneviève Bourret, Douglas Mental Health University Institute [Montréal], McGill University, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Universität Zürich [Zürich] (UZH), McGill University and Genome Quebec Innovation Centre, McGill University = Université McGill [Montréal, Canada], Universität Zürich [Zürich] = University of Zurich (UZH), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Zurich, and Ernst, Carl
- Subjects
Adult ,Male ,0301 basic medicine ,Bisulfite sequencing ,UFSP13-4 Dynamics of Healthy Aging ,Customized MiSeq sequencing ,Computational biology ,Multiplexed barcoding of target amplicon libraries ,Biology ,DNA sequencing ,Multiplexed PCR-directed BS-amplicons ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,1311 Genetics ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Genetics ,Humans ,Sulfites ,5-hydroxymethylcytosine ,Methylated DNA immunoprecipitation ,5-methylcytosine ,10093 Institute of Psychology ,Methodology Article ,Sequence Analysis, DNA ,DNA Methylation ,3. Good health ,Bisulfite ,genomic DNA ,5-Methylcytosine ,030104 developmental biology ,chemistry ,DNA methylation ,1305 Biotechnology ,Next-generation sequencing ,Targeted bisulfite sequencing ,DNA microarray ,150 Psychology ,Oxidation-Reduction ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Background Epigenetic modifications of DNA, such as 5-methylcytosine and 5-hydroxymethycytosine, play important roles in development and disease. Here, we present a cost-effective and versatile methodology for the analysis of DNA methylation in targeted genomic regions, which comprises multiplexed, PCR-based preparation of bisulfite DNA libraries followed by customized MiSeq sequencing. Results Using bisulfite and oxidative bisulfite conversion of DNA, we have performed multiplexed targeted sequencing to analyse several kilobases of genomic DNA in up to 478 samples, and achieved high coverage data of 5-methylcytosine and 5-hydroxymethycytosine at single-base resolution. Our results demonstrate the ability of this methodology to detect all levels of cytosine modifications at greater than 100× coverage in large sample sets at low cost compared to other targeted methods. Conclusions This approach can be applied to multiple settings, from candidate gene to clinical studies, and is especially useful for validation of differentially methylated or hydroxymethylated regions following whole-genome analyses. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3489-9) contains supplementary material, which is available to authorized users.
- Published
- 2017
24. Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations
- Author
-
Justin T. Warner, Marie-Anne Brundler, John F. Kuttesch, Fabio Rotondo, Joon Hyuk Choi, Megan K. Dishop, J. W. Neal, Archana Srivastava, William D. Foulkes, Adam J. Esbenshade, Thomas S. Jacques, Nelly Sabbaghian, Arie Perry, Heinz Leichter, Margaret Zacharin, Philippe Maeder, Márta Korbonits, Steffen Albrecht, Thomas W. McLean, Dorothée Bouron-Dal Soglio, Pierre Lepage, Nancy Hamel, Evan Weber, Heidi Traunecker, Trevor Cole, François Plourde, Eva Horvath, Sung Hye Park, Kalman Kovacs, Leanne de Kock, Cheri Deal, Megan M. Kelsey, and John R. Priest
- Subjects
Ribonuclease III ,Somatic cell ,Thoracic ,DNA Mutational Analysis ,Pituitary neoplasm ,medicine.disease_cause ,Germline ,DEAD-box RNA Helicases ,Fatal Outcome ,Neoplasms ,OMIM : Online Mendelian Inheritance in Man ,2.1 Biological and endogenous factors ,Aetiology ,Child ,Tomography ,Cancer ,Pediatric ,Genetics ,Mutation ,Magnetic Resonance Imaging ,Immunohistochemistry ,X-Ray Computed ,Pedigree ,Treatment Outcome ,Child, Preschool ,Blastoma ,Radiography, Thoracic ,Clinical Sciences ,Biology ,Article ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Rare Diseases ,Germline mutation ,Clinical Research ,medicine ,Humans ,Pituitary Neoplasms ,Genetic Testing ,Preschool ,Germ-Line Mutation ,DICER1 Syndrome ,Neurology & Neurosurgery ,Complex and Mixed ,Human Genome ,Neurosciences ,Infant ,medicine.disease ,Neoplasms, Complex and Mixed ,Radiography ,Neurology (clinical) ,Tomography, X-Ray Computed - Abstract
Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis.
- Published
- 2014
25. Dans les embarras de Rouen. Le transport de l’armée britannique à l’Ouest en 1914-1918
- Author
-
Pierre Lepage
- Subjects
First world war ,transport ,Première guerre mondiale ,General Medicine ,Rouen - Abstract
Les accords franco-britanniques nés de l’Entente cordiale de l’année 1904 laissent espérer la participation d’un Corps expéditionnaire britannique aux côtés de l’armée française dans l’hypothèse où l’Empire allemand se livrerait à une agression armée contre la France ou contre le royaume de Belgique. En pareil cas l’état-major français a étudié un plan de transport du contingent britannique débarqué initialement dans les ports du Havre, de Rouen et de Boulogne et acheminé vers le front de bataille par les réseaux ferroviaires français. Entre août 1914 et novembre 1918, l’armée française comme l’armée britannique s’adaptent à la dimension industrielle de la guerre. Elle implique la mise en œuvre d’une énorme logistique et son transport, particulièrement complexes dans la région de Rouen et lors de l’engagement britannique massif sur la Somme en 1916. Il s’ensuit sur les réseaux ferroviaires très surchargés du Nord et de l’État des difficultés d’exploitation marqués par une crise des matériels roulants et par les travaux massifs conduits par les compagnies de sapeurs des chemins de fer et les sections de chemins de fer de campagne. Le trafic dépasse parfois les limites de la saturation. Le service automobile, un expédient initialement, conquiert peu à peu une place prépondérante stratégiquement, notamment aux moments décisifs des batailles de 1918. Sur le plan des relations humaines, les commissaires militaires et techniques sont solidaires et les rapports des régulateurs militaires français avec leurs homologues britanniques sont cordiaux mais les relations entre les dirigeants des deux réseaux du Nord et de l’État sont difficiles. La priorité accordée aux transports de guerre ne peut occulter le climat de concurrence commerciale qui existait avant-guerre entre les deux compagnies notamment en Haute-Normandie. La suggestion avancée par les militaires d’un réseau unifié conduit le gouvernement français à reprendre la main à la fin de 1917 par la création d’un ministère des Transports, puis à confier l’autorité sur les réseaux ferroviaires au ministère des Travaux publics, agissant par délégation du ministre de la Guerre, gage d’une meilleure efficacité dans la gestion de ces réseaux confrontés à de graves difficultés financières et techniques par suite des épreuves d’un conflit interminable. The Franco-British agreements resulting of the Entente Cordiale of 1904 suggested a British Expeditionary Corps involvement alongside the French Army in case of an armed aggression of France or of Belgian Kingdom by the German Empire. For such a case, the French Staff had studied a transportation plan of the British contingent originally landed in the ports of Le Havre, Rouen and Boulogne and routed to the front of battle by the French rail networks. From August 1914 to November 1918, the French army and the British army coped with the industrial dimension of the war. It brought to implement enormous capabilities in the field of logistics and transport, particularly complex in the region of Rouen and during the massive British engagement on the Somme in 1916. On the overloaded “Nord” and “État” networks, this resulted in operating problems related to rolling stock shortage and to massive works carried out by the sappers of the Engineers Railway companies and Field Railway sections. Traffic sometimes exceeded the limits of saturation. Mechanical Transport, initially an expedient, conquered a prominent strategic role, notably during the decisive moments of the battles of 1918. On the human level, the military and technical commissioners remained supportive of each other’s while the relationships of French military regulators with their British counterparts were cordial. On the contrary, the leaders of the “Nord” and “État” networks had difficulties to work together. The priority given to war transportation could not overshadow the climate of commercial competition that existed before the war between the two companies, especially in Haute-Normandie. The suggestion made by the military of a unified network led the French Government to take over at the end of 1917, firstly by the creation of a Ministry of transportation, then entrusting the authority on the rail networks to the Ministry of public works, by delegation of the Minister of war. It was the guarantee of greater efficiency in the management of these networks, which, before long, would face serious financial and technical difficulties caused by an endless conflict.
- Published
- 2014
26. Hommage à Sylvie Vincent (1941-2020)
- Author
-
Pierre Lepage, Laurent Girouard, Rita Mestokosho, Gérald McKenzie, Laurent Jérôme, and Nelcya Delanoë
- Subjects
Automotive Engineering - Published
- 2019
27. L’otite externe nécrosante progressive : place de l’imagerie
- Author
-
Quentin Lisan, Pierre Lepage, Stanislas Ballivet de Régloix, Olga Maurin, Marc Raynal, and Yoann Pons
- Subjects
Tomography x ray computed ,medicine.anatomical_structure ,Osteolysis ,business.industry ,X ray computed ,Middle ear ,Medicine ,General Medicine ,Nuclear medicine ,business ,medicine.disease - Abstract
La Presse Medicale - In Press.Proof corrected by the author Available online since mardi 30 septembre 2014
- Published
- 2014
28. La paralysie faciale périphérique
- Author
-
E Ukkola-Pons, C. Champagne, M Kossowski, Pierre Lepage, Yoann Pons, S. Ballivet de Régloix, and Marc Raynal
- Subjects
medicine.medical_specialty ,Palsy ,business.industry ,Motor nerve ,Anastomosis ,medicine.disease ,Facial nerve ,Diagnosis of exclusion ,Peripheral ,Surgery ,stomatognathic diseases ,Ophthalmology ,Facial muscles ,medicine.anatomical_structure ,Bell's palsy ,medicine ,business - Abstract
Facial palsy can be defined as a decrease in function of the facial nerve, the primary motor nerve of the facial muscles. When the facial palsy is peripheral, it affects both the superior and inferior areas of the face as opposed to central palsies, which affect only the inferior portion. The main cause of peripheral facial palsies is Bell's palsy, which remains a diagnosis of exclusion. The prognosis is good in most cases. In cases with significant cosmetic sequelae, a variety of surgical procedures are available (such as hypoglossal-facial anastomosis, temporalis myoplasty and Tenzel external canthopexy) to rehabilitate facial aesthetics and function.
- Published
- 2013
29. Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas
- Author
-
Peter Hauser, László Bognár, Alfredo Staffa, Almos Klekner, Xiaoyang Liu, Djihad Hadjadj, Stephan Busche, Miklós Garami, Adam Fleming, Adam M. Fontebasso, Marcel Kool, David T.W. Jones, Jeremy Schwartzentruber, Jacek Majewski, Stefan M. Pfister, Krzystof Zakrzewski, Nada Jabado, Noha Gerges, Dominik Sturm, Hendrik Witt, Steffen Albrecht, Dong Anh Khuong-Quang, Pierre Lepage, Pawel P. Liberski, Alexandre Montpetit, Damien Faury, Gelareh Zadeh, Andrey Korshunov, and Magdalena Zakrzewska
- Subjects
medicine.disease_cause ,Cohort Studies ,Histones ,High-grade glioma ,0302 clinical medicine ,Exome ,Child ,Exome sequencing ,Pediatric ,0303 health sciences ,Mutation ,Brain Neoplasms ,Age Factors ,Epigenetic ,Glioma ,Orvostudományok ,Middle Aged ,3. Good health ,030220 oncology & carcinogenesis ,Histone methyltransferase ,Histone Methyltransferases ,Adult ,IDH1 ,Adolescent ,H3K36 methylation ,Clinical Neurology ,Biology ,Klinikai orvostudományok ,Methylation ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,SETD2 ,medicine ,Humans ,Epigenetics ,030304 developmental biology ,Original Paper ,Infant ,Histone-Lysine N-Methyltransferase ,medicine.disease ,Case-Control Studies ,Cancer research ,Neurology (clinical) ,Neoplasm Grading - Abstract
Recurrent mutations affecting the histone H3.3 residues Lys27 or indirectly Lys36 are frequent drivers of pediatric high-grade gliomas (over 30 % of HGGs). To identify additional driver mutations in HGGs, we investigated a cohort of 60 pediatric HGGs using whole-exome sequencing (WES) and compared them to 543 exomes from non-cancer control samples. We identified mutations in SETD2, a H3K36 trimethyltransferase, in 15 % of pediatric HGGs, a result that was genome-wide significant (FDR = 0.029). Most SETD2 alterations were truncating mutations. Sequencing the gene in this cohort and another validation cohort (123 gliomas from all ages and grades) showed SETD2 mutations to be specific to high-grade tumors affecting 15 % of pediatric HGGs (11/73) and 8 % of adult HGGs (5/65) while no SETD2 mutations were identified in low-grade diffuse gliomas (0/45). Furthermore, SETD2 mutations were mutually exclusive with H3F3A mutations in HGGs (P = 0.0492) while they partly overlapped with IDH1 mutations (4/14), and SETD2-mutant tumors were found exclusively in the cerebral hemispheres (P = 0.0055). SETD2 is the only H3K36 trimethyltransferase in humans, and SETD2-mutant tumors showed a substantial decrease in H3K36me3 levels (P
- Published
- 2013
30. Iron Refractory Iron Deficiency Anemia: Presentation With Hyperferritinemia and Response to Oral Iron Therapy
- Author
-
Karin E. Finberg, Nada Jabado, Jacek Majewski, Jeremy Schwartzentruber, Pierre Lepage, Dong-Anh Khuong-Quang, and Mark Westerman
- Subjects
Male ,Adolescent ,Genotype ,Anemia ,Iron ,Microcytic anemia ,DNA Mutational Analysis ,Mutation, Missense ,Administration, Oral ,Case Report ,Compound heterozygosity ,medicine ,Humans ,Exome ,Child ,Exome sequencing ,Genetic testing ,Chromosome Aberrations ,Anemia, Hypochromic ,Anemia, Iron-Deficiency ,medicine.diagnostic_test ,business.industry ,Genetic Carrier Screening ,Anemia, Refractory ,Serine Endopeptidases ,Membrane Proteins ,medicine.disease ,Long-Term Care ,Hypochromic microcytic anemia ,Iron-deficiency anemia ,Child, Preschool ,Ferritins ,Pediatrics, Perinatology and Child Health ,Immunology ,Female ,business ,Follow-Up Studies - Abstract
Iron-refractory iron-deficiency anemia (IRIDA) is an autosomal recessive disorder caused by mutations in TMPRSS6. Patients have hypochromic microcytic anemia refractory to oral iron and are only partially responsive to parenteral iron administration. We report a French-Canadian kindred in which 2 siblings presented in early childhood with severe microcytic anemia, hypoferremia, and hyperferritinemia. Both children have been successfully treated solely with low-dose oral iron since diagnosis. Clinical and biological presentation did not fit any previously described genetic iron-deficiency anemia. Whole exome sequencing identified in both patients compound heterozygous mutations of TMPRSS6 leading to p.G442R and p.E522K, 2 mutations previously reported to cause classic IRIDA, and no additional mutations in known iron-regulatory genes. Thus, the phenotype associated with the unique combination of mutations uncovered in both patients expands the spectrum of disease associated with TMPRSS6 mutations to include iron deficiency anemia that is accompanied by hyperferritinemia at initial presentation and is responsive to continued oral iron therapy. Our results have implications for genetic testing in early childhood iron deficiency anemia. Importantly, they emphasize that whole exome sequencing can be used as a diagnostic tool and greatly facilitate the elucidation of the genetic basis of unusual clinical presentations, including hypomorphic mutations or compound heterozygosity leading to different phenotypes in known Mendelian diseases.
- Published
- 2013
31. Sternohyoid muscles for reconstruction after thyroid cartilage anterior partial resection
- Author
-
Anna Pamela Dela, Cruz, Marc, Remacle, Jerôme, Keghian, Pierre, Lepage, and Florence, Rogister
- Subjects
Male ,Sternum ,Thyroid Cartilage ,Hyoid Bone ,Thyroidectomy ,Humans ,Female ,Middle Aged ,Plastic Surgery Procedures - Published
- 2016
32. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
- Author
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Andreas von Deimling, Hendrik Witt, Arnulf Pekrun, André Nantel, Krzystof Zakrzewski, Volker Hovestadt, Wolfram Scheurlen, Andrey Korshunov, Martin Ebinger, Marc Zapatka, Natalie Jäger, Tobias Rausch, Wolfgang Roggendorf, Michael C. Frühwald, Peter Lichter, Almos Klekner, David T.W. Jones, Andreas E. Kulozik, Martin U. Schuhmann, Elke Pfaff, Olaf Witt, Marina Ryzhova, Martje Tönjes, V. Peter Collins, Steffen Albrecht, Cindy Zhang, Koichi Ichimura, Uri Tabori, Damien Faury, Marcel Kool, David Malkin, Peter Hauser, Dong Anh Khuong Quang, Karine Jacob, Pedro Castelo-Branco, Till Milde, Jeremy Schwartzentruber, Jan O. Korbel, Abhijit Guha, Anders Lindroth, Peter M. Siegel, Matthias Dürken, CM Kramm, Guido Reifenberger, Miklós Garami, Jeffrey Atkinson, Jacek Majewski, Adam M. Fontebasso, Pierre Lepage, Nada Jabado, Pawel P. Liberski, Alexandre Montpetit, Jörg Felsberg, Stefan M. Pfister, Thomas Hielscher, Magdalena Zakrzewska, Carolin Konermann, László Bognár, Xiaoyang Liu, Christoph Plass, Dominik Sturm, and Zhifeng Dong
- Subjects
X-linked Nuclear Protein ,DNA Mutational Analysis ,Molecular Sequence Data ,medicine.disease_cause ,Histones ,Histone H3 ,medicine ,Humans ,Exome ,Child ,ATRX ,Pericentric heterochromatin ,Adaptor Proteins, Signal Transducing ,Genetics ,H3 K27M Mutation ,Mutation ,Multidisciplinary ,Base Sequence ,biology ,Gene Expression Profiling ,DNA Helicases ,Nuclear Proteins ,Telomere ,Chromatin Assembly and Disassembly ,Chromatin ,H3F3B ,Histone ,biology.protein ,Tumor Suppressor Protein p53 ,Glioblastoma ,Co-Repressor Proteins ,Molecular Chaperones - Abstract
Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.
- Published
- 2012
33. Vestibular Schwannoma and Fitness to Fly
- Author
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Marc Raynal, M Kossowski, Iris Hunkemöller, Yoann Pons, and Pierre Lepage
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hearing loss ,Population ,Deafness ,Audiology ,Disability Evaluation ,Young Adult ,Vertigo ,otorhinolaryngologic diseases ,medicine ,Humans ,Videonystagmography ,education ,Aged ,Balance (ability) ,education.field_of_study ,medicine.diagnostic_test ,biology ,business.industry ,Public Health, Environmental and Occupational Health ,Retrospective cohort study ,Neuroma, Acoustic ,Middle Aged ,biology.organism_classification ,Test (assessment) ,Vestibular Diseases ,Aerospace Medicine ,Female ,medicine.symptom ,business ,Tinnitus - Abstract
Introduction: When a pilot is referred for vestibular schwannoma (VS), his or her fitness to fly may be questioned. The objective of this retrospective study was to describe a series of VS cases in a pilot population and to discuss their fitness to fly options. Methods: Between September 2002 and March 2010, the ENT/Head and Neck Surgery Department of the National Pilot Expertise Center conducted nearly 120,000 expert consultations for 40,000 pilots. We examined the files of 10 pilots who were referred to our 2 national experts for VS. Results: At the time of the expert consultation, hypoacusis was present in nine cases (four with total deafness), tinnitus in one case, and vertigo in nine cases. In our series, only 2 of the 10 pilots experienced a negative impact on their fitness to fly. Discussion: Decisions on fitness to fly were based on several factors: minimally disturbed audition, i.e., less than a 35-dB hearing loss with a good speech discrimination score; good balance, i.e., no reported difficulties; no spontaneous nystagmus recorded on videonystagmography (VNG); no postural deviation; and a normal head-shaking test. The delay and the VS's evolution between diagnosis and expert consultation are important because the selection of a treatment to control VS is critical in minimizing the possible associated complications. When a pilot is referred for VS, his or her fitness to fly is determined by the size of the tumor, balance, auditory status, and the follow-up results of these findings. The complications that may arise from VS treatments must also be considered.
- Published
- 2010
34. Spartacus attending the 2005 AAAI conference
- Author
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Froduald Kabanza, Serge Caron, P. Frenette, Pierre Lepage, A. Ponchon, Y. Brosseau, Jean-Marc Valin, Frederic Gagnon, M.-A. Roux, P. Moisan, Patrick M. Giguère, Carle Côté, Dominic Létourneau, Eric Beaudry, Yan Morin, Clément Raïevsky, and François Michaud
- Subjects
Personal robot ,Social robot ,business.industry ,Computer science ,Mobile robot ,Mobile robot navigation ,Robot control ,Artificial Intelligence ,Human–computer interaction ,Key (cryptography) ,Robot ,System integration ,Artificial intelligence ,business - Abstract
Spartacus is our robot entry in the 2005 AAAI Mobile Robot Challenge, making a robot attend the National Conference on Artificial Intelligence. Designing robots that are capable of interacting with humans in real-life settings can be considered the ultimate challenge when it comes to intelligent autonomous systems. One key issue is the integration of multiple modalities (e.g., mobility, physical structure, navigation, vision, audition, dialogue, reasoning). Such integration increases the diversity and also the complexity of interactions the robot can generate. It also makes it difficult to monitor how such increased capabilities are used in unconstrained conditions, whether it is done while the robot is in operation of afterwards. This paper reports solutions and findings resulting from our hardware, software and decisional integration work on Spartacus. It also outlines perspectives in making intelligent and interaction capabilities evolve for autonomous robots.
- Published
- 2006
35. Coordinated Maneuvering of Automated Vehicles in Platoons
- Author
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François Michaud, Pierre Lepage, N. Gaubert, P. Frenette, and Dominic Létourneau
- Subjects
Engineering ,business.industry ,Mechanical Engineering ,Control engineering ,Robotics ,Mobile robot ,Computer Science Applications ,Range (aeronautics) ,Automotive Engineering ,Obstacle avoidance ,Robot ,Platoon ,Artificial intelligence ,business ,Intelligent transportation system ,Collision avoidance - Abstract
To eventually have automated vehicles operate in platoons, it is necessary to study what information each vehicle must have and to whom it must communicate for safe and efficient maneuvering in all possible conditions. This paper formulates the problem in terms of sensing and communicated information. By emulating platoons using a group of mobile robots, the authors demonstrate the feasibility of maneuvers (such as entering, exiting, and recuperating from an accident) using different distributed coordination strategies. The coordination strategies studied range from no communication to unidirectional or bidirectional exchanges between vehicles and to fully centralized decision by the leading vehicle. One particularity of this paper is that instead of assuming that the platoon leader or all vehicles globally monitor what is going on, only the vehicles involved in a particular maneuver are concerned, distributing decisions locally among the platoon. This paper reports experimental trials using robots having limited and directional perception of other things, using vision and obstacle avoidance sensing. Results confirm the feasibility of the coordination strategies in different conditions and various uses of communicated information to compensate for sensing limitations
- Published
- 2006
36. Mutation and biochemical analysis of patients belonging to the cblB complementation class of vitamin B12-dependent methylmalonic aciduria
- Author
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Jamie C. Tirone, Amelie Villeneuve, C. Melissa Dobson, Roy A. Gravel, Abigail B. Gradinger, David S. Rosenblatt, David Watkins, Alexandre Montpetit, Jordan P. Lerner-Ellis, and Pierre Lepage
- Subjects
Male ,Genotype ,Endocrinology, Diabetes and Metabolism ,Nonsense mutation ,Biology ,medicine.disease_cause ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,Methylmalonyl-CoA ,Genetics ,medicine ,Humans ,Missense mutation ,Child ,Molecular Biology ,Cells, Cultured ,Mutation ,Alkyl and Aryl Transferases ,Methylmalonyl-CoA mutase ,Infant, Newborn ,Infant ,Molecular biology ,Complementation ,Vitamin B 12 ,Phenotype ,Methylmalonic aciduria ,chemistry ,Child, Preschool ,Female ,CBLB ,Metabolism, Inborn Errors ,Methylmalonic Acid - Abstract
Methylmalonic aciduria, cblB type (OMIM 251110) is an inborn error of vitamin B(12) metabolism that occurs due to mutations in the MMAB gene. MMAB encodes the enzyme ATP:cobalamin adenosyltransferase, which catalyzes the synthesis of the coenzyme adenosylcobalamin required for the activity of the mitochondrial enzyme methylmalonyl CoA mutase (MCM). MCM catalyzes the isomerization of methylmalonyl CoA to succinyl CoA. Deficient MCM activity results in methylmalonic aciduria and a susceptibility to life-threatening acidotic crises. The MMAB gene was sequenced from genomic DNA from a panel of 35 cblB patients, including five patients previously investigated. Nineteen MMAB mutations were identified, including 13 previously unknown mutations. These included 11 missense mutations, two duplications, one deletion, four splice-site mutations, and one nonsense mutation. None of these mutations was identified in 100 control alleles. Most of the missense mutations (9/11) were clustered in exon 7; many of these affected amino acid residues that are part of the probable active site of the enzyme. One previously described mutation, c.556C >T (p.R186W), was particularly common, accounting for 33% of pathogenic alleles. It was seen almost exclusively in patients of European background and was typically associated with presentation in the first year of life.
- Published
- 2006
37. Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type
- Author
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Pierre Lepage, Johanna M. Rommens, Gail V Dunbar, Peter D. Pawelek, Emily Moras, Kenneth Morgan, Eric A. Shoubridge, Angela R Hosack, T. Mary Fujiwara, James W. Coulton, David S. Rosenblatt, Hana Antonicka, Daniel Leclerc, Carole Doré, Roy A. Gravel, Vince Forgetta, C. Melissa Dobson, Chantal F. Morel, Jamie C. Tirone, David Watkins, Jordan P. Lerner-Ellis, and Janet L Atkinson
- Subjects
Protein Folding ,Molecular Sequence Data ,Homocystinuria ,Locus (genetics) ,Biology ,Cobalamin ,Cell Line ,chemistry.chemical_compound ,Bacterial Proteins ,Genetic linkage ,Genetics ,medicine ,Humans ,Amino Acid Sequence ,Conserved Sequence ,Chromosome Mapping ,Membrane Proteins ,Fibroblasts ,Disease gene identification ,medicine.disease ,MMACHC ,Vitamin B 12 ,Haplotypes ,chemistry ,Methylmalonic aciduria ,Structural Homology, Protein ,Mutation ,CBLC ,Carrier Proteins ,Oxidoreductases ,Metabolism, Inborn Errors ,Methylmalonic Acid - Abstract
Methylmalonic aciduria and homocystinuria, cblC type (OMIM 277400), is the most common inborn error of vitamin B(12) (cobalamin) metabolism, with about 250 known cases. Affected individuals have developmental, hematological, neurological, metabolic, ophthalmologic and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. The cblC locus was mapped to chromosome region 1p by linkage analysis. We refined the chromosomal interval using homozygosity mapping and haplotype analyses and identified the MMACHC gene. In 204 individuals, 42 different mutations were identified, many consistent with a loss of function of the protein product. One mutation, 271dupA, accounted for 40% of all disease alleles. Transduction of wild-type MMACHC into immortalized cblC fibroblast cell lines corrected the cellular phenotype. Molecular modeling predicts that the C-terminal region of the gene product folds similarly to TonB, a bacterial protein involved in energy transduction for cobalamin uptake.
- Published
- 2005
38. Multi-Modal Locomotion Robotic Platform Using Leg-Track-Wheel Articulations
- Author
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Mathieu Millette, Jonathan Bisson, Yan Morin, Marie-Christine Tremblay, Yann Bergeron, Martin Arsenault, Richard Cadrin, Frederic Gagnon, Marc-Antoine Legault, Serge Caron, Dominic Létourneau, François Michaud, Pierre Lepage, and Jean-Francois Pare
- Subjects
Embedded software ,Modal ,Iterative design ,Artificial Intelligence ,Computer science ,Orientation (computer vision) ,Stair climbing ,Process (computing) ,Robot ,Control engineering ,Modularity ,Simulation ,ComputingMethodologies_COMPUTERGRAPHICS - Abstract
Other than from its sensing and processing capabilities, a mobile robotic platform can be limited in its use by its ability to move in the environment. Legs, tracks and wheels are all efficient means of ground locomotion that are most suitable in different situations. Legs allow to climb over obstacles and change the height of the robot, modifying its viewpoint of the world. Tracks are efficient on uneven terrains or on soft surfaces (snow, mud, etc.), while wheels are optimal on flat surfaces. Our objective is to work on a new concept capable of combining different locomotion mechanisms to increase the locomotion capabilities of the robotic platform. The design we came up with, called AZIMUT, is symmetrical and is made of four independent leg-track-wheel articulations. It can move with its articulations up, down or straight, allowing the robot to deal with three-dimensional environments. AZIMUT is also capable of moving sideways without changing its orientation, making it omnidirectional. By putting sensors on these articulations, the robot can also actively perceive its environment by changing the orientation of its articulations. Designing a robot with such capabilities requires addressing difficult design compromises, with measurable impacts seen only after integrating all of the components together. Modularity at the structural, hardware and embedded software levels, all considered concurrently in an iterative design process, reveals to be key in the design of sophisticated mobile robotic platforms.
- Published
- 2005
39. Mutations in theMMAAgene in patients with thecblAdisorder of vitamin B12metabolism
- Author
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David Watkins, Daniel Leclerc, David S. Rosenblatt, Timothy Wai, C. Melissa Dobson, Jamie C. Tirone, Pierre Lepage, Jordan P. Lerner-Ellis, Carole Doré, and Roy A. Gravel
- Subjects
Genetics ,0303 health sciences ,Mutation ,Haplotype ,Biology ,medicine.disease_cause ,Molecular biology ,Stop codon ,3. Good health ,Complementation ,03 medical and health sciences ,Restriction enzyme ,Exon ,0302 clinical medicine ,medicine ,Missense mutation ,Gene ,030217 neurology & neurosurgery ,Genetics (clinical) ,030304 developmental biology - Abstract
Mutations in the MMAA gene on human chromosome 4q31.21 result in vitamin B12-responsive methylmalonic aciduria (cblA complementation group) due to deficiency in the synthesis of adenosylcobalamin. Genomic DNA from 37 cblA patients, diagnosed on the basis of cellular adenosylcobalamin synthesis, methylmalonyl–coenzyme A (CoA) mutase function, and complementation analysis, was analyzed for deleterious mutations in the MMAA gene by DNA sequencing of exons and flanking sequences. A total of 18 novel mutations were identified, bringing the total number of mutations identified in 37 cblA patients to 22. A total of 13 mutations result in premature stop codons; three are splice site defects; and six are missense mutations that occur at highly conserved residues. Eight of these mutations were common to two or more individuals. One mutation, c.433C>T (R145X), represents 43% of pathogenic alleles and a common haplotype was identified. Restriction endonuclease or heteroduplex diagnostic tests were designed to confirm mutations. None of the sequence changes identified in cblA patients were found in 100 alleles from unrelated control individuals. Hum Mutat 24:509–516, 2004. © 2004 Wiley-Liss, Inc.
- Published
- 2004
40. A Combinatorial Network of Evolutionarily ConservedMyelin Basic ProteinRegulatory Sequences Confers Distinct Glial-Specific Phenotypes
- Author
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Thomas J. Hudson, Luc Jasmin, Wayel Orfali, Pierre Lepage, Hooman F. Farhadi, Webb Miller, Alan C. Peterson, Hana C. Friedman, and Reza Forghani
- Subjects
Cholera Toxin ,Hypoxanthine Phosphoribosyltransferase ,Molecular Sequence Data ,Development/Plasticity/Repair ,Gene Expression ,Mice, Transgenic ,Mice ,Myelin ,Genes, Reporter ,Sequence Homology, Nucleic Acid ,Genes, Regulator ,medicine ,Animals ,Humans ,Remyelination ,Cells, Cultured ,Conserved Sequence ,Plant Proteins ,Genetics ,Base Sequence ,biology ,General Neuroscience ,Cell Differentiation ,Myelin Basic Protein ,Saporins ,Phenotype ,Oligodendrocyte ,Myelin basic protein ,Cell biology ,Mice, Inbred C57BL ,Oligodendroglia ,medicine.anatomical_structure ,Regulatory sequence ,Myelin maintenance ,Gene Targeting ,Ribosome Inactivating Proteins, Type 1 ,biology.protein ,Female ,Homologous recombination ,Neuroglia ,Demyelinating Diseases - Abstract
Myelin basic protein (MBP) is required for normal myelin compaction and is implicated in both experimental and human demyelinating diseases. In this study, as an initial step in defining the regulatory network controllingMBPtranscription, we located and characterized the function of evolutionarily conserved regulatory sequences. Long-range human-mouse sequence comparison revealed over 1 kb of conserved noncodingMBP5′ flanking sequence distributed into four widely spaced modules ranging from 0.1 to 0.4 kb. We demonstrate first that a controlled strategy of transgenesis provides an effective means to assign and compare qualitative and quantitativein vivoregulatory programs. Using this strategy, single-copy reporter constructs, designed to evaluate the regulatory significance of modular and intermodular sequences, were introduced by homologous recombination into the mousehprt(hypoxanthine-guanine phosphoribosyltransferase) locus. The proximal modules M1 and M2 confer comparatively low-level oligodendrocyte expression primarily limited to early postnatal development, whereas the upstream M3 confers high-level oligodendrocyte expression extending throughout maturity. Furthermore, constructs devoid of M3 fail to target expression to newly myelinating oligodendrocytes in the mature CNS. Mutation of putative Nkx6.2/Gtx sites within M3, although not eliminating oligodendrocyte targeting, significantly decreases transgene expression levels. High-level and continuous expression is conferred to myelinating or remyelinating Schwann cells by M4. In addition, when isolated from surroundingMBPsequences, M3 confers transient expression to Schwann cells elaborating myelin. These observations define thein vivoregulatory roles played by conserved noncodingMBPsequences and lead to a combinatorial model in which different regulatory modules are engaged during primary myelination, myelin maintenance, and remyelination.
- Published
- 2003
41. Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics
- Author
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Vamsi K. Mootha, Eric S. Lander, Amelie Villeneuve, Fenghao Xu, Jakob Bunkenborg, Majbrit Hjerrild, Pierre Lepage, Robert Sladek, Terrye Delmonte, Charles Morin, Grant A. Mitchell, Michael R. Reich, John D. Rioux, Thomas J. Hudson, Matthias Mann, Brian D. Robinson, and Kathleen Miller
- Subjects
Proteomics ,Genetics ,Mitochondrial DNA ,Candidate gene ,Multidisciplinary ,Molecular Sequence Data ,Haplotype ,Cytochrome-c Oxidase Deficiency ,Genomics ,Biological Sciences ,Biology ,Mitochondria ,Neoplasm Proteins ,Mutation ,OMIM : Online Mendelian Inheritance in Man ,Humans ,Human genome ,Amino Acid Sequence ,RNA, Messenger ,Gene ,Functional genomics - Abstract
Identifying the genes responsible for human diseases requires combining information about gene position with clues about biological function. The recent availability of whole-genome data sets of RNA and protein expression provides powerful new sources of functional insight. Here we illustrate how such data sets can expedite disease-gene discovery, by using them to identify the gene causing Leigh syndrome, French-Canadian type (LSFC, Online Mendelian Inheritance in Man no. 220111), a human cytochrome c oxidase deficiency that maps to chromosome 2p16-21. Using four public RNA expression data sets, we assigned to all human genes a “score” reflecting their similarity in RNA-expression profiles to known mitochondrial genes. Using a large survey of organellar proteomics, we similarly classified human genes according to the likelihood of their protein product being associated with the mitochondrion. By intersecting this information with the relevant genomic region, we identified a single clear candidate gene, LRPPRC . Resequencing identified two mutations on two independent haplotypes, providing definitive genetic proof that LRPPRC indeed causes LSFC. LRPPRC encodes an mRNA-binding protein likely involved with mtDNA transcript processing, suggesting an additional mechanism of mitochondrial pathophysiology. Similar strategies to integrate diverse genomic information can be applied likewise to other disease pathways and will become increasingly powerful with the growing wealth of diverse, functional genomics data.
- Published
- 2003
42. Variation in genomic landscape of clear cell renal cell carcinoma across Europe
- Author
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Christine Carreira, Yasser Riazalhosseini, Alexander Mazur, Sharon Jackson, Alvis Brazma, Lars Egevad, Simon Heath, Ivana Holcatova, Rosamonde E. Banks, Graham Byrnes, Doris Lechner, Jeremy Sehmoun, Liliana Greger, Konstantin G. Skryabin, Anne Cambon-Thomsen, Pierre Lepage, Jon Cartledge, David Zaridze, Johan Rung, Madeleine Arseneault, Behnoush Abedi-Ardekani, Egor Prokhortchouk, Marie Navratilova, Antoine Daunay, Mehran Karimzadeh, Jiri Zavadil, Victor Renault, Eugenia S. Boulygina, Dana Mates, Emmanuel Tubacher, Juris Viksna, Ivo Gut, Hélène Blanché, Magdalena B. Wozniak, Artem V. Artemov, Viorel Jinga, Jörg Tost, Naveen S. Vasudev, Patricia Harnden, Morag Seywright, Alexandre How-Kit, Paul Brennan, Ghislaine Scelo, Lenka Foretova, G Mark Lathrop, Marta Gut, Edgars Celms, Martins Opmanis, Jing Su, Anush Moukeria, Mar Gonzàlez-Porta, Marie-Therese Bihoreau, Guillaume Bourque, Antonin Brisuda, Sergey M. Rastorguev, Louis Letourneau, Peter Selby, Andris Zarins, Mathieu Bourgey, Mario Foglio, and Artem V. Nedoluzhko
- Subjects
Adult ,Male ,Oncogene Proteins, Fusion ,RNA Splicing ,General Physics and Astronomy ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Transcriptome ,Phosphatidylinositol 3-Kinases ,Mutation Rate ,medicine ,Humans ,Epigenetics ,Carcinoma, Renal Cell ,Aged ,Aged, 80 and over ,Genetics ,Focal Adhesions ,Mutation ,Multidisciplinary ,Genome, Human ,Gene Expression Profiling ,Genetic Variation ,Genomics ,Sequence Analysis, DNA ,General Chemistry ,Middle Aged ,medicine.disease ,Human genetics ,3. Good health ,Europe ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Clear cell renal cell carcinoma ,Female ,Carcinogenesis ,Clear cell ,Signal Transduction - Abstract
The incidence of renal cell carcinoma (RCC) is increasing worldwide, and its prevalence is particularly high in some parts of Central Europe. Here we undertake whole-genome and transcriptome sequencing of clear cell RCC (ccRCC), the most common form of the disease, in patients from four different European countries with contrasting disease incidence to explore the underlying genomic architecture of RCC. Our findings support previous reports on frequent aberrations in the epigenetic machinery and PI3K/mTOR signalling, and uncover novel pathways and genes affected by recurrent mutations and abnormal transcriptome patterns including focal adhesion, components of extracellular matrix (ECM) and genes encoding FAT cadherins. Furthermore, a large majority of patients from Romania have an unexpected high frequency of A:T>T:A transversions, consistent with exposure to aristolochic acid (AA). These results show that the processes underlying ccRCC tumorigenesis may vary in different populations and suggest that AA may be an important ccRCC carcinogen in Romania, a finding with major public health implications.
- Published
- 2014
43. From teletraining to telehomecare — Design of mobile and multi-stream telehealth systems
- Author
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Pierre Lepage, Simon Brière, François Michaud, Dominic Létourneau, Mathieu Hamel, and Michel Tousignant
- Subjects
Teletraining ,Process management ,Multimedia ,Relation (database) ,Computer science ,media_common.quotation_subject ,Multi stream ,Telehealth ,computer.software_genre ,Information and Communications Technology ,Telerehabilitation ,Quality (business) ,computer ,Telehomecare ,media_common - Abstract
Telehealth success relies on the ability of information and communication technologies (ICT) to maximize the quality of care provided remotely, i.e., providing diagnostics and treatments of the same quality compared to face-to-face or conventional means, and maximize the benefits for the patients, the clinicians and the system of care. Because of the specific nature of health-related processes, successful development of telehealth technologies must be driven by clinical and application needs that are not addressed by currently available ICT. In this paper, we present two telehealth systems developed in two different contexts, one for teletraining of surgical procedures, and one for telerehabilitation, and from which common requirements can be identified for the development of a more generic platform. This paper also situates where these systems are in relation to their stage of development and their assessment as telehealth technologies.
- Published
- 2014
44. A Distal Upstream Enhancer from theMyelin Basic ProteinGene Regulates Expression in Myelin-Forming Schwann Cells
- Author
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Priscila Valera, Thomas J. Hudson, Hooman F. Farhadi, Alan C. Peterson, David R. Foran, Pierre Lepage, L. Garofalo, Reza Forghani, and Irene Tretjakoff
- Subjects
Transgene ,Schwann cell ,Mice, Transgenic ,Regulatory Sequences, Nucleic Acid ,Biology ,Mice ,Myelin ,Genes, Reporter ,Gene expression ,medicine ,Animals ,Peripheral Nerves ,RNA, Messenger ,Transgenes ,ARTICLE ,Promoter Regions, Genetic ,Enhancer ,Early Growth Response Protein 2 ,Myelin Sheath ,Regulation of gene expression ,Mice, Inbred C3H ,Binding Sites ,General Neuroscience ,Gene Expression Regulation, Developmental ,Myelin Basic Protein ,Sequence Analysis, DNA ,beta-Galactosidase ,Molecular biology ,Myelin basic protein ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Enhancer Elements, Genetic ,medicine.anatomical_structure ,Spinal Cord ,nervous system ,Regulatory sequence ,Mutagenesis, Site-Directed ,biology.protein ,Schwann Cells ,Transcription Factors - Abstract
In peripheral nerves, large caliber axons are ensheathed by myelin-elaborating Schwann cells. Multiple lines of evidence demonstrate that expression of the genes encoding myelin structural proteins occurs in Schwann cells in response to axonal instructions. To gain further insight into the mechanisms controlling myelin gene expression, we used reporter constructs in transgenic mice to search for the DNA elements that regulate themyelin basic protein(MBP) gene. Through thisin vivoinvestigation, we provide evidence for the participation of multiple, widely distributed, positive and negative elements in the overall control ofMBPexpression. Notably, all constructs bearing a 0.6 kb far-upstream sequence, designated Schwann cell enhancer 1 (SCE1), expressed at high levels in myelin-forming Schwann cells. In addition, robust targeting activity conferred by SCE1 was shown to be independent of otherMBP5′ flanking sequence. These observations suggest that SCE1 will make available a powerful tool to drive transgene expression in myelinating Schwann cells and that a focused analysis of the SCE1 sequence will lead to the identification of transcription factor binding sites that positively regulateMBPexpression.
- Published
- 2001
45. PPM1D Mutations in Circulating White Blood Cells and the Risk for Ovarian Cancer
- Author
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Mark D. Minden, Barry P. Rosen, Pierre Lepage, John McLaughlin, Harvey A. Risch, Steven A. Narod, and Mohammad R. Akbari
- Subjects
Oncology ,Canada ,Heterozygote ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Risk Assessment ,Breast cancer ,Risk Factors ,Internal medicine ,Leukocytes ,Odds Ratio ,Phosphoprotein Phosphatases ,medicine ,Humans ,Genetic Predisposition to Disease ,Family history ,First-degree relatives ,Aged ,Proportional Hazards Models ,BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,business.industry ,Incidence ,Hazard ratio ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Protein Phosphatase 2C ,Case-Control Studies ,Mutation ,Female ,business ,Ovarian cancer - Abstract
We compared the frequency of PPM1D mutation in the white blood cells from 1295 ovarian cancer case patients and 834 control subjects. We found a truncating mutation in 20 case patients vs 1 control subject (odds ratio [OR] = 13.07; 95% confidence interval [CI] = 1.75 to 97.55; P < .001). The 12-year mortality of the PPM1D-positive case patients was higher than that of the PPM1D-negative case patients (hazard ratio = 2.02; 95% CI = 1.21 to 3.39; P = .007). Three of the 20 PPM1D carrier case patients had a past history of breast cancer compared with 29 of 1129 noncarriers (OR = 6.69; 95% CI = 1.86 to 24.11; P = .007). The lifetime risks for breast or ovarian cancer among female first-degree relatives of PPM1D mutation carriers were not increased compared with that of case patients without mutations. These observations suggest PPM1D mutations in the mosaic state predispose women to breast and ovarian cancer in the absence of a family history of cancer.
- Published
- 2013
46. ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF
- Author
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Eric S. Lander, Serge B. Melançon, Jean Mathieu, Kenneth Morgan, Andrea Richter, Jocelyne Mercier, James C. Engert, Martin Schalling, Jean-Pierre Bouchard, Thomas J. Hudson, Bing Ge, Pierre Bérubé, Pierre Lepage, and Carole Doré
- Subjects
Molecular Sequence Data ,Arabidopsis ,Sequence alignment ,Biology ,Linkage Disequilibrium ,Homology (biology) ,Mice ,Open Reading Frames ,Exon ,Prevalence ,Genetics ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Gene ,Heat-Shock Proteins ,Spinocerebellar Degenerations ,Base Sequence ,Chromosomes, Human, Pair 13 ,Sequence Homology, Amino Acid ,Reverse Transcriptase Polymerase Chain Reaction ,Haplotype ,Quebec ,Nucleic acid sequence ,Chromosome Mapping ,Autosomal recessive cerebellar ataxia ,Exons ,medicine.disease ,Open reading frame ,Mutation ,Ataxia ,Sequence Alignment - Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.
- Published
- 2000
47. Identification of CD109 as part of the TGF‐β receptor system in human keratinocytes
- Author
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Kenneth W. Finnson, Betty Y. Y. Tam, Kai Liu, Anne Marcoux, Pierre Lepage, Stephane Roy, Albane A. Bizet, and Anie Philip
- Subjects
Keratinocytes ,TGF alpha ,GPI-Linked Proteins ,Transfection ,Biochemistry ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Transforming Growth Factor beta ,Genetics ,medicine ,Humans ,Receptor ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,R-SMAD ,biology ,Binding protein ,Transforming growth factor beta ,TGF beta receptor 2 ,Ligand (biochemistry) ,Recombinant Proteins ,Neoplasm Proteins ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Keratinocyte ,Receptors, Transforming Growth Factor beta ,Biotechnology - Abstract
We have previously reported that keratinocytes defective in glycosylphosphatidylinositol (GPI)-anchor biosynthesis display enhanced TGF-beta responses. These studies implicated the involvement of a 150 kDa GPI-anchored TGF-beta1 binding protein, r150, in modulating TGF-beta signaling. Here, we sought to determine the molecular identity of r150 by affinity purification and microsequencing. Our results identify r150 as CD109, a novel member of the alpha2-macroglobulin (alpha2M)/complement superfamily, whose function has remained obscure. In addition, we have identified a novel CD109 isoform that occurs in the human placenta but not keratinocytes. Biochemical studies show that r150 contains an internal thioester bond, a defining feature of the alpha2M/complement family. Loss and gain of function studies demonstrate that CD109 is a component of the TGF-beta receptor system, and a negative modulator of TGF-beta responses in keratinocytes, as implicated for r150. Our data suggest that CD109 can inhibit TGF-beta signaling independently of ligand sequestration and may exert its effect on TGF-beta signaling by direct modulation of receptor activity. Together, our results linking CD109 function to regulation of TGF-beta signaling suggest that CD109 plays a unique role in the regulation of isoform-specific TGF-beta signaling in keratinocytes.
- Published
- 2006
48. Radioimmunoassay for Cortisol in Pig Saliva and Serum
- Author
-
Allan L. Schaefer, N.J. Cook, Pierre Lepage, and Steven D. Morgan Jones
- Subjects
Antiserum ,endocrine system ,medicine.medical_specialty ,Saliva ,Chromatography ,Radioimmunoassay ,General Chemistry ,Biology ,Endocrinology ,Internal medicine ,medicine ,Cortisone ,General Agricultural and Biological Sciences ,Quantitative analysis (chemistry) ,hormones, hormone substitutes, and hormone antagonists ,Serum cortisol ,Salivary cortisol ,medicine.drug ,Hydrocortisone - Abstract
An “in-house” radioimmunoassay (RIA) procedure utilizing commercial sources of antiserum and radiolabel was developed for the simultaneous measurement of cortisol in serum and saliva from swine. A commercial RIA kit (Incstar) for cortisol was used to validate the in-house procedure for serum measurements. The correlation coefficient (r) between the Incstar kit and the in-house method for serum cortisol was 0.94. The Incstar kit was modified to accommodate measurement of salivary cortisol concentrations and compared to the in-house procedure. The correlation between these procedures was r = 0.81 and best described by a logarithmic (Ln) curve. Salivary cortisol measures by the in-house RIA were significantly higher than those obtained from the modified Incstar kit (p < 0.01), a probable consequence of the different relative cross-reactions of the respective antisera to cortisone and a dilution effect on the kit standards. Keywords: Radioimmunoassay; salivary cortisol; pigs; stress
- Published
- 1997
49. High-Resolution Linkage Map in the Proximity of the Host Resistance LocusCmv1
- Author
-
Pierre Lepage, Philippe Gros, Eric S. Muise, Silvia M. Vidal, and Chantal Depatie
- Subjects
Genetic Markers ,Genetics ,Mice, Inbred BALB C ,Cosegregation ,Genetic Linkage ,Cytomegalovirus ,Chromosome ,Locus (genetics) ,3T3 Cells ,Biology ,Virus Replication ,Genetic recombination ,Molecular biology ,Immunity, Innate ,Chromosomal crossover ,Mice, Inbred C57BL ,Mice ,Phenotype ,Gene mapping ,Genetic linkage ,Genetic marker ,Cytomegalovirus Infections ,Animals - Abstract
The mouse chromosome 6 locus Cmv1 controls replication of mouse Cytomegalovirus (MCMV) in the spleen of the infected host. In our effort to clone Cmv1, we have constructed a high-resolution genetic linkage map in the proximity of the gene. For this, a total of 45 DNA markers corresponding to either cloned genes or microsatellites were mapped within a 7.9-cM interval overlapping the Cmv1 region. We have followed the cosegregation of these markers with respect to Cmv1 in a total of 2248 backcross mice from a preexisting interspecific backcross panel of 281 (Mus spretus x C57BL/6J)F1 x C57BL/6J and 2 novel panels of 989 (A/ J x C57BL6)F1 x A/J and 978 (BALB/c x C57BL/6J)F1 x BALB/c segregating Cmv1. Combined pedigree analysis allowed us to determine the following gene order and intergene distances (in cM) on the distal region of mouse chromosome 6: D6Mit216-(1.9)-D6Mit336-(2.2)- D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp 1/ D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370++ +- (0.3)-Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/ 220/196/195/110-(1.1)-D6Mit25. Therefore, the minimal genetic interval for Cmv1 of 0.7 cM is defined by 13 tightly linked markers including 2 markers, Ly49A and D6Mit370, that did not show recombination with Cmv1 in 1967 meioses analyzed; the proximal limit of the Cmv1 domain was defined by 8 crossovers between Nkrp1/ D6Mit61/135/257/289/338 and Cmv1/Ly49A/D6Mit370, and the distal limit was defined by 5 crossovers between Cmv1/Ly49A/D6Mit370 and Prp/Kap/D6Mit13/111/219. This work demonstrates tight linkage between Cmv1 and genes from the natural killer complex (NKC), such as Nkrp1 and Ly49A, suggesting that Cmv1 may represent an NK cell recognition structure encoded in the NKC region.
- Published
- 1997
50. Whole exome sequencing unravels disease-causing genes in consanguineous families in Qatar
- Author
-
Pierre Lepage, K. Abu Khadija, H. Gamal, S. Zaineddin, R. Ali, Mariam Almuriekhi, L. Hashim, Somayyeh Fahiminiya, Tawfeg Ben-Omran, Jacek Majewski, Zafar Nawaz, Alfredo Staffa, and Jeremy Schwartzentruber
- Subjects
Proband ,Male ,Parents ,Consanguinity ,Biology ,medicine.disease_cause ,Bioinformatics ,Exon ,Genetics ,medicine ,Glycogen storage disease ,Humans ,Disease ,Exome ,Family ,Genetic Predisposition to Disease ,Hurler syndrome ,Qatar ,Genetics (clinical) ,Exome sequencing ,Mutation ,PHEX ,Sequence Analysis, DNA ,medicine.disease ,Pedigree ,Female - Abstract
Whole exome sequencing (WES) has greatly facilitated the identification of causal mutations for diverse human genetic disorders. We applied WES as a molecular diagnostic tool to identify disease-causing genes in consanguineous families in Qatar. Seventeen consanguineous families with diverse disorders were recruited. Initial mutation screening of known genes related to the clinical diagnoses did not reveal the causative mutations. Using WES approach, we identified the definitive disease-causing mutations in four families: (i) a novel nonsense homozygous (c.1034C>G) in PHKG2 causing glycogen storage disease type 9C (GSD9C) in a male with initial diagnosis of GSD3; (ii) a novel homozygous 1-bp deletion (c.915del) in NSUN2 in a male proband with Noonan-like syndrome; (iii) a homozygous SNV (c.1598C>G) in exon 11 of IDUA causing Hurler syndrome in a female proband with unknown clinical diagnosis; (iv) a de novo known splicing mutation (c.1645+1G>A) in PHEX in a female proband with initial diagnosis of autosomal recessive hypophosphatemic rickets. Applying WES as a diagnostic tool led to the unambiguous identification of disease-causing mutations in phenotypically complex disorders or correction of the initial clinical diagnosis in ˜25% of our cases.
- Published
- 2013
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