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1. Massive detection of cryptic recessive genetic defects in dairy cattle mining millions of life histories

Author

Besnard, Florian, Guintard, Ana, Grohs, Cécile, Guzylack-Piriou, Laurence, Cano, Margarita, Escouflaire, Clémentine, Hozé, Chris, Leclerc, Hélène, Buronfosse, Thierry, Dutheil, Lucie, Jourdain, Jeanlin, Barbat, Anne, Fritz, Sébastien, Deloche, Marie-Christine, Remot, Aude, Gaussères, Blandine, Clément, Adèle, Bouchier, Marion, Contat, Elise, Relun, Anne, Plassard, Vincent, Rivière, Julie, Péchoux, Christine, Vilotte, Marthe, Eche, Camille, Kuchly, Claire, Charles, Mathieu, Boulling, Arnaud, Viard, Guillaume, Minéry, Stéphanie, Barbey, Sarah, Birbes, Clément, Danchin-Burge, Coralie, Launay, Frédéric, Mattalia, Sophie, Allais-Bonnet, Aurélie, Ravary, Bérangère, Millemann, Yves, Guatteo, Raphaël, Klopp, Christophe, Gaspin, Christine, Iampietro, Carole, Donnadieu, Cécile, Milan, Denis, Arcangioli, Marie-Anne, Boussaha, Mekki, Foucras, Gilles, Boichard, Didier, and Capitan, Aurélien

Published
2024
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3. Massive detection of cryptic recessive genetic defects in dairy cattle mining millions of life histories

Author

Florian Besnard, Ana Guintard, Cécile Grohs, Laurence Guzylack-Piriou, Margarita Cano, Clémentine Escouflaire, Chris Hozé, Hélène Leclerc, Thierry Buronfosse, Lucie Dutheil, Jeanlin Jourdain, Anne Barbat, Sébastien Fritz, Marie-Christine Deloche, Aude Remot, Blandine Gaussères, Adèle Clément, Marion Bouchier, Elise Contat, Anne Relun, Vincent Plassard, Julie Rivière, Christine Péchoux, Marthe Vilotte, Camille Eche, Claire Kuchly, Mathieu Charles, Arnaud Boulling, Guillaume Viard, Stéphanie Minéry, Sarah Barbey, Clément Birbes, Coralie Danchin-Burge, Frédéric Launay, Sophie Mattalia, Aurélie Allais-Bonnet, Bérangère Ravary, Yves Millemann, Raphaël Guatteo, Christophe Klopp, Christine Gaspin, Carole Iampietro, Cécile Donnadieu, Denis Milan, Marie-Anne Arcangioli, Mekki Boussaha, Gilles Foucras, Didier Boichard, and Aurélien Capitan

Subjects
Data science, Recessive genetic defects, Livestock, Large-scale genotyping, Whole-genome sequencing, Inbreeding depression, Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Dairy cattle breeds are populations of limited effective size, subject to recurrent outbreaks of recessive defects that are commonly studied using positional cloning. However, this strategy, based on the observation of animals with characteristic features, may overlook a number of conditions, such as immune or metabolic genetic disorders, which may be confused with pathologies of environmental etiology. Results We present a data mining framework specifically designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. Conclusions The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

Published
2024
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4. Impact of SARS-CoV-2 spike stability and RBD exposure on antigenicity and immunogenicity

Author

Lucy Rutten, Maarten Swart, Annemart Koornneef, Pascale Bouchier, Sven Blokland, Ava Sadi, Jarek Juraszek, Aneesh Vijayan, Sonja Schmit-Tillemans, Johan Verspuij, Ying Choi, Chenandly E. Daal, Aditya Perkasa, Shessy Torres Morales, Sebenzile K. Myeni, Marjolein Kikkert, Jeroen Tolboom, Daniëlle van Manen, Harmjan Kuipers, Hanneke Schuitemaker, Roland Zahn, and Johannes P. M. Langedijk

Subjects
Medicine, Science
Abstract

Abstract The spike protein (S) of SARS-CoV-2 induces neutralizing antibodies and is the key component of current COVID-19 vaccines. The most efficacious COVID-19 vaccines are genetically-encoded spikes with a double proline substitution in the hinge region to stabilize S in the prefusion conformation (S-2P). A subunit vaccine can be a valuable addition to mRNA and viral vector-based vaccines but requires high stability of spike. In addition, further stabilization of the prefusion conformation of spike might improve immunogenicity. To test this, five spike proteins were designed and characterized, ranging from low to high stability. The immunogenicity of these proteins was assessed in mice, demonstrating that a spike (S-closed-2) with a high melting temperature, which still allowed ACE2 binding, induced the highest neutralization titers against homologous and heterologous strains (up to 16-fold higher than the least stabilized spike). In contrast, the most stable spike variant (S-locked), in which the receptor binding domains (RBDs) were locked in a closed conformation and thus not able to breathe, induced relatively low neutralizing antibody titers against heterologous strains. These data demonstrate that S protein stabilization with RBDs exposing highly conserved epitopes may be needed to increase the immunogenicity of spike proteins for future COVID-19 vaccines.

Published
2024
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10. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry

Author

Claireaux, Mathieu, Robinot, Rémy, Kervevan, Jérôme, Patgaonkar, Mandar, Staropoli, Isabelle, Brelot, Anne, Nouël, Alexandre, Gellenoncourt, Stacy, Tang, Xian, Héry, Mélanie, Volant, Stevenn, Perthame, Emeline, Avettand-Fenoël, Véronique, Buchrieser, Julian, Cokelaer, Thomas, Bouchier, Christiane, Ma, Laurence, Boufassa, Faroudy, Hendou, Samia, Libri, Valentina, Hasan, Milena, Zucman, David, de Truchis, Pierre, Schwartz, Olivier, Lambotte, Olivier, and Chakrabarti, Lisa A.

Published
2022
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11. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry

Author

Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, Anne Brelot, Alexandre Nouël, Stacy Gellenoncourt, Xian Tang, Mélanie Héry, Stevenn Volant, Emeline Perthame, Véronique Avettand-Fenoël, Julian Buchrieser, Thomas Cokelaer, Christiane Bouchier, Laurence Ma, Faroudy Boufassa, Samia Hendou, Valentina Libri, Milena Hasan, David Zucman, Pierre de Truchis, Olivier Schwartz, Olivier Lambotte, and Lisa A. Chakrabarti

Subjects
Science
Abstract

Here, Claireaux et al. show that people who naturally control HIV infection express lower levels of the viral co-receptor CCR5 in specific CD4+ T cells, and that this results from mutations or receptor internalization by CD4+ T cell-produced chemokines.

Published
2022
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16. Stabilizing the closed SARS-CoV-2 spike trimer

Author

Jarek Juraszek, Lucy Rutten, Sven Blokland, Pascale Bouchier, Richard Voorzaat, Tina Ritschel, Mark J. G. Bakkers, Ludovic L. R. Renault, and Johannes P. M. Langedijk

Subjects
Science
Abstract

SARS-CoV-2 S protein prematurely refolds to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yield. Here, Juraszek et al. present a stable SARS-CoV-2 S-closed protein variant with increased expression and correct folding, predominantly in closed prefusion conformation.

Published
2021
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17. TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages

Author

Daria Bottai, Wafa Frigui, Fadel Sayes, Mariagrazia Di Luca, Dalila Spadoni, Alexandre Pawlik, Marina Zoppo, Mickael Orgeur, Varun Khanna, David Hardy, Sophie Mangenot, Valerie Barbe, Claudine Medigue, Laurence Ma, Christiane Bouchier, Arianna Tavanti, Gerald Larrouy-Maumus, and Roland Brosch

Subjects
Science
Abstract

Mycobacterium tuberculosis (Mtb) modern strains emerged from a common progenitor after the loss of Mtb-specific deletion 1 region (TbD1). Here, the authors show that deletion of TbD1 correlates with enhanced Mtb virulence in animal models, mirroring the development of hypoxic granulomas in human disease progression.

Published
2020
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18. Une typologie des élevages bovins de l'Etat de Colima au Mexique : première étape du diagnostic

Author

Norma P. Cervantes, Jean-Philippe Choisis, A. Bouchier, and Philippe Lhoste

Subjects
Bovin, Analyse de données, Recherche, Systeme d'elevage, Developpement de l'elevage, Mexique, Animal culture, SF1-1100
Abstract

Les auteurs présentent une enquête et son traitement destinés à l'élaboration d'une typologie des systèmes d'élevage bovin de l'Etat de Colima au Mexique. La typologie est proposée sur la base de différentes méthodes d'analyse manuelle ou multidimensionnelle: il s'avère intéressant de comparer les différentes descriptions de la diversité du réel obtenues par ces méthodes qui se complètent. Outre son objectif premier d'établissement de la typologie, cette phase d'enquête, préalable au développement du programme de recherche chez les éleveurs, a permis de préciser les principales contraintes à l'amélioration de l'élevage bovin et de proposer un premier schéma de l'organisation de la production bovine de l'Etat de Colima. Ces premiers résultats ont permis d'orienter la poursuite des travaux de recherche-développement sur l'élevage.

Published
1986
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19. Une typologie d'exploitations agropastorales au Siné-Saloum, Sénégal

Author

J.P.G. Orsini, Philippe Lhoste, A. Bouchier, A. Faye, and L. Niang

Subjects
Analyse de données, Système d'exploitation agricole, Conduite des herbages, Énergie animale, Système agropastoral, Structure agricole, Animal culture, SF1-1100
Abstract

Les auteurs ont utilisé des méthodes d'analyse multidimensionnelle (analyse factorielle des correspondances, classification hiérarchique) pour réaliser une typologie d'exploitations agropastorales sur la base d'une enquête menée au Siné-Saloum, Sénégal, sur 245 exploitations. Les variables retenues concernent principalement la taille de l'exploitation (nombre d'actifs, surfaces cultivées), le cheptel de traction, le troupeau bovin extensif et les petits ruminants. A partir des 4 groupes de la typologie, une interprétation est donnée des principaux modes de fonctionnement des exploitations et des hypothèses sont discutées quant à la dynamique de ces exploitations, en relation notamment avec les modes de capitalisation et avec la traction bovine

Published
1985
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21. Unipolar Peptidoglycan Synthesis in the Rhizobiales Requires an Essential Class A Penicillin-Binding Protein

Author

Michelle A. Williams, Alena Aliashkevich, Elizaveta Krol, Erkin Kuru, Jacob M. Bouchier, Jonathan Rittichier, Yves V. Brun, Michael S. VanNieuwenhze, Anke Becker, Felipe Cava, and Pamela J. B. Brown

Subjects
Microbiology, QR1-502
Abstract

While the structure and function of the bacterial cell wall are well conserved, the mechanisms responsible for cell wall biosynthesis during elongation are variable. It is increasingly clear that rod-shaped bacteria use a diverse array of growth strategies with distinct spatial zones of cell wall biosynthesis, including lateral elongation, unipolar growth, bipolar elongation, and medial elongation.

Published
2021
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26. Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response

Author

Karla E. Lopez and Lisa Bouchier-Hayes

Subjects
caspases, DNA damage, genomic instability, cell cycle, apoptosis, Cytology, QH573-671
Abstract

Members of the caspase family are well known for their roles in the initiation and execution of cell death. Due to their function in the removal of damaged cells that could otherwise become malignant, caspases are important players in the DNA damage response (DDR), a network of pathways that prevent genomic instability. However, emerging evidence of caspases positively or negatively impacting the accumulation of DNA damage in the absence of cell death demonstrates that caspases play a role in the DDR that is independent of their role in apoptosis. This review highlights the apoptotic and non-apoptotic roles of caspases in the DDR and how they can impact genomic stability and cancer treatment.

Published
2022
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28. Caspase-2 Substrates: To Apoptosis, Cell Cycle Control, and Beyond

Author

Alexandra N. Brown-Suedel and Lisa Bouchier-Hayes

Subjects
caspase-2, PIDD, Raidd, BID, MDM2, apoptosis, Biology (General), QH301-705.5
Abstract

Caspase-2 belongs to the caspase family of proteins responsible for essential cellular functions including apoptosis and inflammation. Uniquely, caspase-2 has been identified as a tumor suppressor, but how it regulates this function is still unknown. For many years, caspase-2 has been considered an “orphan” caspase because, although it is able to induce apoptosis, there is an abundance of conflicting evidence that questions its necessity for apoptosis. Recent evidence supports that caspase-2 has non-apoptotic functions in the cell cycle and protection from genomic instability. It is unclear how caspase-2 regulates these opposing functions, which has made the mechanism of tumor suppression by caspase-2 difficult to determine. As a protease, caspase-2 likely exerts its functions by proteolytic cleavage of cellular substrates. This review highlights the known substrates of caspase-2 with a special focus on their functional relevance to caspase-2’s role as a tumor suppressor.

Published
2020
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30. Gene flow contributes to diversification of the major fungal pathogen Candida albicans

Author

Jeanne Ropars, Corinne Maufrais, Dorothée Diogo, Marina Marcet-Houben, Aurélie Perin, Natacha Sertour, Kevin Mosca, Emmanuelle Permal, Guillaume Laval, Christiane Bouchier, Laurence Ma, Katja Schwartz, Kerstin Voelz, Robin C. May, Julie Poulain, Christophe Battail, Patrick Wincker, Andrew M. Borman, Anuradha Chowdhary, Shangrong Fan, Soo Hyun Kim, Patrice Le Pape, Orazio Romeo, Jong Hee Shin, Toni Gabaldon, Gavin Sherlock, Marie-Elisabeth Bougnoux, and Christophe d’Enfert

Subjects
Science
Abstract

The fungal pathogen Candida albicans can undergo a parasexual process that may contribute to genetic diversity, but its actual relevance is unclear. Here, Ropars et al. analyse the genomic sequences of 182 C. albicans isolates collected worldwide and find evidence of gene flow and thus parasexuality in nature.

Published
2018
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31. Short genome report of cellulose-producing commensal Escherichia coli 1094

Author

Joaquin Bernal-Bayard, Laura Gomez-Valero, Aimee Wessel, Varun Khanna, Christiane Bouchier, and Jean-Marc Ghigo

Subjects
E. coli, Commensal, Biofilm, Cellulose, Extracellular matrix, Bcs operon, Genetics, QH426-470
Abstract

Abstract Bacterial surface colonization and biofilm formation often rely on the production of an extracellular polymeric matrix that mediates cell-cell and cell-surface contacts. In Escherichia coli and many Betaproteobacteria and Gammaproteobacteria cellulose is often the main component of the extracellular matrix. Here we report the complete genome sequence of the cellulose producing strain E. coli 1094 and compare it with five other closely related genomes within E. coli phylogenetic group A. We present a comparative analysis of the regions encoding genes responsible for cellulose biosynthesis and discuss the changes that could have led to the loss of this important adaptive advantage in several E. coli strains. Data deposition: The annotated genome sequence has been deposited at the European Nucleotide Archive under the accession number PRJEB21000.

Published
2018
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34. Genomic history of the seventh pandemic of cholera in Africa

Author

Weill, François-Xavier, Domman, Daryl, Njamkepo, Elisabeth, Tarr, Cheryl, Rauzier, Jean, Fawal, Nizar, Keddy, Karen H., Salje, Henrik, Moore, Sandra, Mukhopadhyay, Asish K., Bercion, Raymond, Luquero, Francisco J., Ngandjio, Antoinette, Dosso, Mireille, Monakhova, Elena, Garin, Benoit, Bouchier, Christiane, Pazzani, Carlo, Mutreja, Ankur, Grunow, Roland, Sidikou, Fati, Bonte, Laurence, Breurec, Sébastien, Damian, Maria, Njanpop-Lafourcade, Berthe-Marie, Sapriel, Guillaume, Page, Anne-Laure, Hamze, Monzer, Henkens, Myriam, Chowdhury, Goutam, Mengel, Martin, Koeck, Jean-Louis, Fournier, Jean-Michel, Dougan, Gordon, Grimont, Patrick A. D., Parkhill, Julian, Holt, Kathryn E., Piarroux, Renaud, Ramamurthy, Thandavarayan, Quilici, Marie-Laure, and Thomson, Nicholas R.

Published
2017

35. Integrated view of Vibrio cholerae in the Americas

Author

Domman, Daryl, Quilici, Marie-Laure, Dorman, Matthew J., Njamkepo, Elisabeth, Mutreja, Ankur, Mather, Alison E., Delgado, Gabriella, Morales-Espinosa, Rosario, Grimont, Patrick A. D., Lizárraga-Partida, Marcial Leonardo, Bouchier, Christiane, Aanensen, David M., Kuri-Morales, Pablo, Tarr, Cheryl L., Dougan, Gordon, Parkhill, Julian, Campos, Josefina, Cravioto, Alejandro, Weill, François-Xavier, and Thomson, Nicholas R.

Published
2017

37. A surrogate marker of piperaquine-resistant Plasmodium falciparum malaria: a phenotype–genotype association study

Author

Witkowski, Benoit, Duru, Valentine, Khim, Nimol, Ross, Leila S, Saintpierre, Benjamin, Beghain, Johann, Chy, Sophy, Kim, Saorin, Ke, Sopheakvatey, Kloeung, Nimol, Eam, Rotha, Khean, Chanra, Ken, Malen, Loch, Kaknika, Bouillon, Anthony, Domergue, Anais, Ma, Laurence, Bouchier, Christiane, Leang, Rithea, Huy, Rekol, Nuel, Grégory, Barale, Jean-Christophe, Legrand, Eric, Ringwald, Pascal, Fidock, David A, Mercereau-Puijalon, Odile, Ariey, Frédéric, and Ménard, Didier

Published
2017
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39. Genomic insights into the 2016–2017 cholera epidemic in Yemen

Author

Weill, François-Xavier, Domman, Daryl, Njamkepo, Elisabeth, Almesbahi, Abdullrahman A., Naji, Mona, Nasher, Samar Saeed, Rakesh, Ankur, Assiri, Abdullah M., Sharma, Naresh Chand, Kariuki, Samuel, Pourshafie, Mohammad Reza, Rauzier, Jean, Abubakar, Abdinasir, Carter, Jane Y., Wamala, Joseph F., Seguin, Caroline, Bouchier, Christiane, Malliavin, Thérèse, Bakhshi, Bita, Abulmaali, Hayder H. N., Kumar, Dhirendra, Njoroge, Samuel M., Malik, Mamunur Rahman, Kiiru, John, Luquero, Francisco J., Azman, Andrew S., Ramamurthy, Thandavarayan, Thomson, Nicholas R., and Quilici, Marie-Laure

Published
2019
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40. The Influence of Habitat on Viral Diversity in Neotropical Rodent Hosts

Author

Sourakhata Tirera, Benoit de Thoisy, Damien Donato, Christiane Bouchier, Vincent Lacoste, Alain Franc, and Anne Lavergne

Subjects
virome, alpha diversity, rodents, Amazonia, viral ecology, viral phylogenies, Microbiology, QR1-502
Abstract

Rodents are important reservoirs of numerous viruses, some of which have significant impacts on public health. Ecosystem disturbances and decreased host species richness have been associated with the emergence of zoonotic diseases. In this study, we aimed at (a) characterizing the viral diversity in seven neotropical rodent species living in four types of habitats and (b) exploring how the extent of environmental disturbance influences this diversity. Through a metagenomic approach, we identified 77,767 viral sequences from spleen, kidney, and serum samples. These viral sequences were attributed to 27 viral families known to infect vertebrates, invertebrates, plants, and amoeba. Viral diversities were greater in pristine habitats compared with disturbed ones, and lowest in peri-urban areas. High viral richness was observed in savannah areas. Differences in these diversities were explained by rare viruses that were generally more frequent in pristine forest and savannah habitats. Moreover, changes in the ecology and behavior of rodent hosts, in a given habitat, such as modifications to the diet in disturbed vs. pristine forests, are major determinants of viral composition. Lastly, the phylogenetic relationships of four vertebrate-related viral families (Polyomaviridae, Flaviviridae, Togaviridae, and Phenuiviridae) highlighted the wide diversity of these viral families, and in some cases, a potential risk of transmission to humans. All these findings provide significant insights into the diversity of rodent viruses in Amazonia, and emphasize that habitats and the host’s dietary ecology may drive viral diversity. Linking viral richness and abundance to the ecology of their hosts and their responses to habitat disturbance could be the starting point for a better understanding of viral emergence and for future management of ecosystems.

Published
2021
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41. New Susceptibility Locus for Rheumatoid Arthritis Suggested by a Genome-Wide Linkage Study

Author

Cornelis, Francois, Faure, Sabine, Martinez, Maria, Fritz, Pierre, Dib, Colette, Alves, Helena, Barrera, Pilar, De Vries, Niek, Balsa, Alejandro, Pascual-Salcedo, Dora, Maenaut, Kristin, Westhovens, Rene, Migliorini, Paola, Tran, Tuyet-Hoa, Delaye, Arnaud, Prince, Nathalie, Lefevre, Caroline, Thomas, Gaelle, Poirier, Murielle, Soubigou, Stephane, Alibert, Olivier, Lasbleiz, Sandra, Fouix, Sylvaine, Bouchier, Christiane, Liote, Frederic, Loste, Marie-Noelle, Lepage, Virginia, Charron, Dominique, Gyapay, Gabor, Lopes-Vaz, Antonio, Kuntz, Daniel, Bardin, Thomas, and Weissenbach, Jean

Published
1998

42. Characterization of reverse-engineered anti-PF4 stereotypic antibodies derived from serum of patients with VITT

Author

Wang, Jing Jing, van der Neut Kolfschoten, Marijn, Rutten, Lucy, Armour, Bridie, Tan, Chee Wee, Chataway, Tim, Bos, Rinke, Koornneef, Annemart, Abeywickrema, Pravien, Kapur, Rick, Porcelijn, Leendert, Khalifa, Midia, Sadi, Ava, Bouchier, Pascale, Kourkouta, Eleni, Perkasa, Aditya, Kwaks, Ted, Zahn, Roland, Solforosi, Laura, and Gordon, Tom P.

Published
2024
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49. Unmasking the ancestral activity of integron integrases reveals a smooth evolutionary transition during functional innovation

Author

Jose Antonio Escudero, Celine Loot, Vincent Parissi, Aleksandra Nivina, Christiane Bouchier, and Didier Mazel

Subjects
Science
Abstract

The integron integrases have evolved to perform recombination of single and double stranded DNA. Here the authors show that the ancestral pathway is still functional at double stranded sites, revealing the evolution towards the modern resolution pathway.

Published
2016
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50. Limited Mitochondrial Permeabilization Causes DNA Damage and Genomic Instability in the Absence of Cell Death

Author

Ichim, Gabriel, Lopez, Jonathan, Ahmed, Shafiq U., Muthalagu, Nathiya, Giampazolias, Evangelos, Delgado, M. Eugenia, Haller, Martina, Riley, Joel S., Mason, Susan M., Athineos, Dimitris, Parsons, Melissa J., van de Kooij, Bert, Bouchier-Hayes, Lisa, Chalmers, Anthony J., Rooswinkel, Rogier W., Oberst, Andrew, Blyth, Karen, Rehm, Markus, Murphy, Daniel J., and Tait, Stephen W.G.

Published
2015
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