Search

Your search keyword '"Rollat-Farnier, Pierre-Antoine"' showing total 38 results
Start Over Author "Rollat-Farnier, Pierre-Antoine"
38 results on '"Rollat-Farnier, Pierre-Antoine"'

1. A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia

Author

Vanhoye, Xavier, Bardel, Claire, Rimbert, Antoine, Moulin, Philippe, Rollat-Farnier, Pierre-Antoine, Muntaner, Manon, Marmontel, Oriane, Dumont, Sabrina, Charrière, Sybil, Cornélis, François, Ducluzeau, Pierre Henri, Fonteille, Annie, Nobecourt, Estelle, Peretti, Noël, Schillo, Franck, Wargny, Matthieu, Cariou, Bertrand, Meirhaeghe, Aline, and Di Filippo, Mathilde

Published
2023
Full Text
View/download PDF

4. Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts

Author

Campion, Dominique, Dartigues, Jean-Francois, Deleuze, Jean-François, Genin, Emmanuelle, Lambert, Jean-Charles, Redon, Richard, Allain-Launay, Emma, Bader-Meunier, Brigitte, Belot, Alexandre, Bouayed, Kenza, Burtey, Stephane, Carbasse, Aurélia, Decramer, Stéphane, Despert, Véronique, Fain, Olivier, Fischbach, Michel, Flodrops, Hugues, Galeotti, Caroline, Hachulla, Eric, Hatchuel, Yves, Kleinmann, Jean-Francois, Kone-Paut, Isabelle, Lanteri, Aurélia, Lemelle, Irène, Maillard, Hélène, Maurier, François, Meinzer, Ulrich, Melki, Isabelle, Morell-Dubois, Sandrine, Pagnier, Anne, Piram, Maryam, Ranchin, Bruno, Reumaux, Héloise, Samaille, Charlotte, Sibilia, Jean, Weill, Olivia, Al-Abadi, Eslam, Armon, Kate, Bailey, Kathryn, Beresford, Michael, Brennan, Mary, Ciurtin, Coziana, Gardner-Medwin, Janet, Haslam, Kirsty, Hawley, Daniel, Leahy, Alice, Leone, Valentina, Mewar, Devesh, Moots, Rob, Pilkington, Clarissa, Ramanan, Athimalaipet, Rangaraj, Satyapal, Ratcliffe, Annie, Riley, Philip, Sen, Ethan, Sridhar, Arani, Wilkinson, Nick, Wood, Fiona, Rice, Gillian I, Omarjee, Sulliman Ommar, Rouchon, Quentin, Smith, Eve M D, Moreews, Marion, Tusseau, Maud, Frachette, Cécile, Bournhonesque, Raphael, Thielens, Nicole, Gaboriaud, Christine, Rouvet, Isabelle, Chopin, Emilie, Hoshino, Akihiro, Latour, Sylvain, Cimaz, Rolando, Romagnani, Paula, Malcus, Christophe, Fabien, Nicole, Sarda, Marie-Nathalie, Kassai, Behrouz, Lega, Jean-Christophe, Abou-Jaoude, Pauline, Bruce, Ian N, Simonet, Thomas, Bardel, Claire, Rollat-Farnier, Pierre Antoine, Viel, Sebastien, O'Sullivan, James, Walzer, Thierry, Mathieu, Anne-Laure, Marenne, Gaelle, Ludwig, Thomas, Ellingford, Jamie, Briggs, Tracy A, Beresford, Michael W, and Crow, Yanick J

Published
2020
Full Text
View/download PDF

5. Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia

Author

Rimbert, Antoine, Vanhoye, Xavier, Coulibaly, Dramane, Marrec, Marie, Pichelin, Matthieu, Charrière, Sybil, Peretti, Noël, Valéro, René, Wargny, Matthieu, Carrié, Alain, Lindenbaum, Pierre, Deleuze, Jean-François, Genin, Emmanuelle, Redon, Richard, Rollat-Farnier, Pierre Antoine, Goxe, Didier, Degraef, Gilles, Marmontel, Oriane, Divry, Eléonore, Bigot-Corbel, Edith, Moulin, Philippe, Cariou, Bertrand, and Di Filippo, Mathilde

Published
2020
Full Text
View/download PDF

6. Molecular investigation, using chromosomal microarray and whole exome sequencing, of six patients affected by Williams Beuren syndrome and Autism Spectrum Disorder

Author

Masson, Julie, Demily, Caroline, Chatron, Nicolas, Labalme, Audrey, Rollat-Farnier, Pierre-Antoine, Schluth-Bolard, Caroline, Gilbert-Dussardier, Brigitte, Giuliano, Fabienne, Touraine, Renaud, Tordjman, Sylvie, Verloes, Alain, Testa, Giuseppe, Sanlaville, Damien, Edery, Patrick, Lesca, Gaetan, and Rossi, Massimiliano

Published
2019
Full Text
View/download PDF

7. Familial transmission of chromoanagenesis leads to unpredictable unbalanced rearrangements through meiotic recombination

Author

Masson, Julie, primary, Pebrel‐Richard, Céline, additional, Egloff, Matthieu, additional, Frétigny, Mathilde, additional, Beaumont, Marion, additional, Uguen, Kevin, additional, Rollat‐Farnier, Pierre‐Antoine, additional, Diguet, Flavie, additional, Perthus, Isabelle, additional, Le Gudayer, Gwenaël, additional, Haye, Damien, additional, Dupeyron, Marie‐Noëlle Bonnet, additional, Putoux, Audrey, additional, Raskin‐Champion, Fabienne, additional, Till, Marianne, additional, Chatron, Nicolas, additional, Doray, Bérénice, additional, Bardel, Claire, additional, Vinciguerra, Christine, additional, Sanlaville, Damien, additional, and Schluth‐Bolard, Caroline, additional

Published
2023
Full Text
View/download PDF

8. Alpha Satellite Insertion Close to an Ancestral Centromeric Region

Author

Giannuzzi, Giuliana, Logsdon, Glennis A, Chatron, Nicolas, Miller, Danny E, Reversat, Julie, Munson, Katherine M, Hoekzema, Kendra, Bonnet-Dupeyron, Marie-Noëlle, Rollat-Farnier, Pierre-Antoine, Baker, Carl A, Sanlaville, Damien, Eichler, Evan E, Schluth-Bolard, Caroline, and Reymond, Alexandre

Subjects
Chromosomal Proteins, Non-Histone, ancestral centromere, Centromere, AcademicSubjects/SCI01130, structural variation, Humans, alpha satellite, DNA, Satellite, AcademicSubjects/SCI01180, Centromere Protein B, Discoveries, In Situ Hybridization, Fluorescence
Abstract

Human centromeres are mainly composed of alpha satellite DNA hierarchically organized as higher-order repeats (HORs). Alpha satellite dynamics is shown by sequence homogenization in centromeric arrays and by its transfer to other centromeric locations, for example, during the maturation of new centromeres. We identified during prenatal aneuploidy diagnosis by fluorescent in situ hybridization a de novo insertion of alpha satellite DNA from the centromere of chromosome 18 (D18Z1) into cytoband 15q26. Although bound by CENP-B, this locus did not acquire centromeric functionality as demonstrated by the lack of constriction and the absence of CENP-A binding. The insertion was associated with a 2.8-kbp deletion and likely occurred in the paternal germline. The site was enriched in long terminal repeats and located ∼10 Mbp from the location where a centromere was ancestrally seeded and became inactive in the common ancestor of humans and apes 20–25 million years ago. Long-read mapping to the T2T-CHM13 human genome assembly revealed that the insertion derives from a specific region of chromosome 18 centromeric 12-mer HOR array in which the monomer size follows a regular pattern. The rearrangement did not directly disrupt any gene or predicted regulatory element and did not alter the methylation status of the surrounding region, consistent with the absence of phenotypic consequences in the carrier. This case demonstrates a likely rare but new class of structural variation that we name “alpha satellite insertion.” It also expands our knowledge on alphoid DNA dynamics and conveys the possibility that alphoid arrays can relocate near vestigial centromeric sites.

Published
2021

9. Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Author

Calender, Alain, Rollat Farnier, Pierre Antoine, Buisson, Adrien, Pinson, Stéphane, Bentaher, Abderrazzaq, Lebecque, Serge, Corvol, Harriet, Abou Taam, Rola, Houdouin, Véronique, Bardel, Claire, Roy, Pascal, Devouassoux, Gilles, Cottin, Vincent, Seve, Pascal, Bernaudin, Jean-François, Lim, Clarice X., Weichhart, Thomas, Valeyre, Dominique, Pacheco, Yves, Clement, Annick, Nathan, Nadia, and in the frame of GSF (Groupe Sarcoïdose France)

Published
2018
Full Text
View/download PDF

10. Familial transmission of chromoanagenesis leads to unpredictable unbalanced rearrangements through meiotic recombination

Author

Masson, Julie, primary, Pebrel-Richard, Céline, additional, Egloff, Matthieu, additional, FRETIGNY, MATHILDE, additional, Beaumont, Marion, additional, Uguen, Kevin, additional, Rollat-Farnier, Pierre-Antoine, additional, Diguet, Flavie, additional, Perthus, Isabelle, additional, GUYADER, Gwenaël LE, additional, Haye, Damien, additional, Dupeyron, Marie-Noëlle Bonnet, additional, Putoux, Audrey, additional, Raskin-Champion, Fabienne, additional, Till, Marianne, additional, CHATRON, Nicolas, additional, Doray, Bérénice, additional, Bardel, Claire, additional, VINCIGUERRA, CHRISTINE, additional, Sanlaville, Damien, additional, and Schluth-Bolard, Caroline, additional

Published
2022
Full Text
View/download PDF

11. Complete characterisation of two new large Xq28 duplications involving F8 using whole genome sequencing in patients without haemophilia A

Author

Jourdy, Yohann, primary, Bardel, Claire, additional, Fretigny, Mathilde, additional, Diguet, Flavie, additional, Rollat‐Farnier, Pierre‐Antoine, additional, Mathieu, Marie‐Laure, additional, Labalme, Audrey, additional, Sanlaville, Damien, additional, Edery, Patrick, additional, Vinciguerra, Christine, additional, and Schluth‐Bolard, Caroline, additional

Published
2021
Full Text
View/download PDF

12. Alpha satellite insertion close to an ancestral centromeric region

Author

Giannuzzi, Giuliana, primary, Logsdon, Glennis A., additional, Chatron, Nicolas, additional, Miller, Danny E., additional, Reversat, Julie, additional, Munson, Katherine M., additional, Hoekzema, Kendra, additional, Bonnet-Dupeyron, Marie-Noëlle, additional, Rollat-Farnier, Pierre-Antoine, additional, Baker, Carl A., additional, Sanlaville, Damien, additional, Eichler, Evan E., additional, Schluth-Bolard, Caroline, additional, and Reymond, Alexandre, additional

Published
2021
Full Text
View/download PDF

14. Development of a new expanded next‐generation sequencing panel for genetic diseases involved in dyslipidemia

Author

Marmontel, Oriane, primary, Rollat‐Farnier, Pierre Antoine, additional, Wozny, Anne‐Sophie, additional, Charrière, Sybil, additional, Vanhoye, Xavier, additional, Simonet, Thomas, additional, Chatron, Nicolas, additional, Collin‐Chavagnac, Delphine, additional, Nony, Séverine, additional, Dumont, Sabrina, additional, Mahl, Muriel, additional, Jacobs, Chantal, additional, Janin, Alexandre, additional, Caussy, Cyrielle, additional, Poinsot, Pierre, additional, Tauveron, Igor, additional, Bardel, Claire, additional, Millat, Gilles, additional, Peretti, Noël, additional, Moulin, Philippe, additional, Marçais, Christophe, additional, and Di Filippo, Mathilde, additional

Published
2020
Full Text
View/download PDF

15. The enrichment of breakpoints in late-replicating chromatin provides novel insights into chromoanagenesis mechanisms

Author

Chatron, Nicolas, primary, Giannuzzi, Giuliana, additional, Rollat-Farnier, Pierre-Antoine, additional, Diguet, Flavie, additional, Porcu, Eleonora, additional, Yammine, Tony, additional, Uguen, Kevin, additional, Bellil, Zohra-Lydia, additional, Zillhardt, Julia Lauer, additional, Sorlin, Arthur, additional, Ader, Flavie, additional, Afenjar, Alexandra, additional, Andrieux, Joris, additional, Bardel, Claire, additional, Calpena, Eduardo, additional, Chantot-Bastaraud, Sandra, additional, Callier, Patrick, additional, Chelloug, Nora, additional, Chopin, Emilie, additional, Cordier, Marie-Pierre, additional, Dubourg, Christèle, additional, Faivre, Laurence, additional, Girard, Françoise, additional, Heide, Solveig, additional, Herenger, Yvan, additional, Jaillard, Sylvie, additional, Keren, Boris, additional, Knight, Samantha J. L., additional, Lespinasse, James, additional, Lohmann, Laurence, additional, Marle, Nathalie, additional, Maroofian, Reza, additional, Masurel-Paulet, Alice, additional, Mathieu-Dramard, Michèle, additional, Metay, Corinne, additional, Pagnamenta, Alistair T., additional, Portnoï, Marie-France, additional, Prieur, Fabienne, additional, Rio, Marlène, additional, Siffroi, Jean-Pierre, additional, Valence, Stéphanie, additional, Taylor, Jenny C., additional, Wilkie, Andrew O. M., additional, Edery, Patrick, additional, Reymond, Alexandre, additional, Sanlaville, Damien, additional, and Schluth-Bolard, Caroline, additional

Published
2020
Full Text
View/download PDF

16. Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts

Author

Belot, Alexandre, primary, Rice, Gillian I, additional, Omarjee, Sulliman Ommar, additional, Rouchon, Quentin, additional, Smith, Eve M D, additional, Moreews, Marion, additional, Tusseau, Maud, additional, Frachette, Cécile, additional, Bournhonesque, Raphael, additional, Thielens, Nicole, additional, Gaboriaud, Christine, additional, Rouvet, Isabelle, additional, Chopin, Emilie, additional, Hoshino, Akihiro, additional, Latour, Sylvain, additional, Ranchin, Bruno, additional, Cimaz, Rolando, additional, Romagnani, Paula, additional, Malcus, Christophe, additional, Fabien, Nicole, additional, Sarda, Marie-Nathalie, additional, Kassai, Behrouz, additional, Lega, Jean-Christophe, additional, Decramer, Stéphane, additional, Abou-Jaoude, Pauline, additional, Bruce, Ian N, additional, Simonet, Thomas, additional, Bardel, Claire, additional, Rollat-Farnier, Pierre Antoine, additional, Viel, Sebastien, additional, Reumaux, Héloise, additional, O'Sullivan, James, additional, Walzer, Thierry, additional, Mathieu, Anne-Laure, additional, Marenne, Gaelle, additional, Ludwig, Thomas, additional, Genin, Emmanuelle, additional, Ellingford, Jamie, additional, Bader-Meunier, Brigitte, additional, Briggs, Tracy A, additional, Beresford, Michael W, additional, Crow, Yanick J, additional, Campion, Dominique, additional, Dartigues, Jean-Francois, additional, Deleuze, Jean-François, additional, Lambert, Jean-Charles, additional, Redon, Richard, additional, Allain-Launay, Emma, additional, Belot, Alexandre, additional, Bouayed, Kenza, additional, Burtey, Stephane, additional, Carbasse, Aurélia, additional, Despert, Véronique, additional, Fain, Olivier, additional, Fischbach, Michel, additional, Flodrops, Hugues, additional, Galeotti, Caroline, additional, Hachulla, Eric, additional, Hatchuel, Yves, additional, Kleinmann, Jean-Francois, additional, Kone-Paut, Isabelle, additional, Lanteri, Aurélia, additional, Lemelle, Irène, additional, Maillard, Hélène, additional, Maurier, François, additional, Meinzer, Ulrich, additional, Melki, Isabelle, additional, Morell-Dubois, Sandrine, additional, Pagnier, Anne, additional, Piram, Maryam, additional, Samaille, Charlotte, additional, Sibilia, Jean, additional, Weill, Olivia, additional, Al-Abadi, Eslam, additional, Armon, Kate, additional, Bailey, Kathryn, additional, Beresford, Michael, additional, Brennan, Mary, additional, Ciurtin, Coziana, additional, Gardner-Medwin, Janet, additional, Haslam, Kirsty, additional, Hawley, Daniel, additional, Leahy, Alice, additional, Leone, Valentina, additional, Mewar, Devesh, additional, Moots, Rob, additional, Pilkington, Clarissa, additional, Ramanan, Athimalaipet, additional, Rangaraj, Satyapal, additional, Ratcliffe, Annie, additional, Riley, Philip, additional, Sen, Ethan, additional, Sridhar, Arani, additional, Wilkinson, Nick, additional, and Wood, Fiona, additional

Published
2020
Full Text
View/download PDF

17. Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization

Author

Uguen, Kévin, Jubin, Claire, Duffourd, Yannis, Bardel, Claire, Malan, Valérie, Dupont, Jean‐Michel, El Khattabi, Laila, Chatron, Nicolas, Vitobello, Antonio, Rollat‐Farnier, Pierre‐Antoine, Baulard, Céline, Lelorch, Marc, Leduc, Aurelie, Tisserant, Emilie, Tran Mau‐Them, Frédéric, Danjean, Vincent, Délépine, Marc, Till, Marianne, Meyer, Vincent, LYONNET, Stanislas, Mosca‐Boidron, Anne‐laure, Thevenon, Julien, Faivre, Laurence, Thauvin‐Robinet, Christel, Schluth‐Bolard, Caroline, Boland, Anne, Olaso, Robert, Callier, Patrick, Romana, Serge, Deleuze, Jean‐François, Sanlaville, Damien, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Performance analysis and optimization of LARge Infrastructures and Systems (POLARIS), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'Informatique de Grenoble (LIG), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Service de génétique [Hôpial Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Pôle Couple-Enfant, Département de Génétique et Procréation, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Génétique des Anomalies du Développement (GAD), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Eco-Anthropologie et Ethnobiologie (EAE), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Cytogénétique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), Interactions Arbres-Microorganismes (IAM), Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Laboratoire Information, Milieux, Médias, Médiations - EA 3820 (I3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Université de Toulon (UTLN), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service d'Histologie-Embryologie et Cytogénétique Assistance Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)

Subjects
Whole Genome Sequencing, lcsh:QH426-470, Method, structural variants, Chromosome Disorders, bioinformatics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], genome sequencing, Cytogenetics, lcsh:Genetics, 10X Genomics: Illumina, Intellectual Disability, Genomic Structural Variation, Humans, Abnormalities, Multiple, Genetic Testing, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS
Abstract

Background Structural variants (SVs) include copy number variants (CNVs) and apparently balanced chromosomal rearrangements (ABCRs). Genome sequencing (GS) enables SV detection at base‐pair resolution, but the use of short‐read sequencing is limited by repetitive sequences, and long‐read approaches are not yet validated for diagnosis. Recently, 10X Genomics proposed Chromium, a technology providing linked‐reads to reconstruct long DNA fragments and which could represent a good alternative. No study has compared short‐read to linked‐read technologies to detect SVs in a constitutional diagnostic setting yet. The aim of this work was to determine whether the 10X Genomics technology enables better detection and comprehension of SVs than short‐read WGS. Methods We included 13 patients carrying various SVs. Whole genome analyses were performed using paired‐end HiSeq X sequencing with (linked‐read strategy) or without (short‐read strategy) Chromium library preparation. Two different bioinformatic pipelines were used: Variants are called using BreakDancer for short‐read strategy and LongRanger for long‐read strategy. Variant interpretations were first blinded. Results The short‐read strategy allowed diagnosis of known SV in 10/13 patients. After unblinding, the linked‐read strategy identified 10/13 SVs, including one (patient 7) missed by the short‐read strategy. Conclusion In conclusion, regarding the results of this study, 10X Genomics solution did not improve the detection and characterization of SV., We compared linked‐read and short‐read sequencing in patients with structural variants. We conclude that linked‐read strategy did not improve the detection and characterization of structural variants.

Published
2020
Full Text
View/download PDF

18. Complete characterisation of two new large Xq28 duplications involving F8 using whole genome sequencing in patients without haemophilia A.

Author

Jourdy, Yohann, Bardel, Claire, Fretigny, Mathilde, Diguet, Flavie, Rollat‐Farnier, Pierre‐Antoine, Mathieu, Marie‐Laure, Labalme, Audrey, Sanlaville, Damien, Edery, Patrick, Vinciguerra, Christine, and Schluth‐Bolard, Caroline

Subjects
WHOLE genome sequencing, HEMOPHILIA, CHROMOSOME analysis, GENETIC counseling, GENETIC correlations, DISABILITIES
Abstract

Introduction: Depending on the location of insertion of the gained region, F8 duplications can have variable clinical impacts from benign impact to severe haemophilia A phenotype. Aim: To characterize two large Xq28 duplications involving F8 incidentally detected by chromosome microarray analysis (CMA) in two patients presenting severe intellectual disability but no history of bleeding disorder. Methods: Whole genome sequencing (WGS) was performed in order to characterize the two large Xq28 duplications at nucleotide level. Results: In patient 1, a 60–73 kb gained region encompassing the exons 23–26 of F8 and SMIM9 was inserted at the int22h‐2 locus following a non‐homologous recombination between int22h‐1 and int22h‐2. We hypothesized that two independent events, micro‐homology‐mediated break‐induced replication (MMBIR) and break‐induced replication (BIR), could be involved in this rearrangement. In patient 2, the CMA found duplication from 101 to 116‐kb long encompassing the exons 16–26 of F8 and SMIM9. The WGS analysis identified a more complex rearrangement with the presence of three genomic junctions. Due to the multiple micro‐homologies observed at breakpoints, a replication‐based mechanism such as fork stalling and template switching (FoSTeS) was greatly suspected. In both cases, these complex rearrangements preserved an intact copy of the F8. Conclusion: This study highlights the value of WGS to characterize the genomic junction at the nucleotide level and ultimately better describe the molecular mechanisms involved in Xq28 structural variations. It also emphasizes the importance of specifying the structure of the genomic gain in order to improve genotype‐phenotype correlation and genetic counselling. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

19. Identification of mobile retrocopies during genetic testing: Consequences for routine diagnosis

Author

Chatron, Nicolas, Cassinari, Kevin, Quenez, Olivier, Baert-Desurmont, Stephanie, Bardel, Claire, Buisine, Marie Pierre, Calpena, Eduardo, Capri, Yline, Corominas Galbany, Jordi, Diguet, F., EDERY, PATRICK, Isidor, Bertrand, Labalme, Audrey, Caignec, Cédric Le, Lecoquierre, Francois, Lindenbaum, Pierre, Rollat Farnier, Pierre Antoine, Simonet, F., Saugier Veber, Pascale, Tabet, Anne-Claude, Toutain, Annick, Wilkie, AOM, Lesca, Gaëtan, Sanlaville, Damien, Nicolas, Gael, Schluth-Bolard, Caroline, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biostatistiques [Lyon], IRCELYON-Microscopie (MICROSCOPIE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, UF de Cytogénétique, AP-HP Hôpital universitaire Robert-Debré [Paris], Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

20. Whole MYBPC3 NGS sequencing as a molecular strategy to improve the efficiency of molecular diagnosis of patients with hypertrophic cardiomyopathy

Author

Janin, Alexandre, primary, Chanavat, Valérie, additional, Rollat‐Farnier, Pierre‐Antoine, additional, Bardel, Claire, additional, Nguyen, Karine, additional, Chevalier, Philippe, additional, Eicher, Jean‐Christophe, additional, Faivre, Laurence, additional, Piard, Juliette, additional, Albert, Emma, additional, Nony, Severine, additional, and Millat, Gilles, additional

Published
2019
Full Text
View/download PDF

21. Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster

Author

Le Caignec, Cédric, primary, Pichon, Olivier, additional, Briand, Annaig, additional, de Courtivron, Benoît, additional, Bonnard, Christian, additional, Lindenbaum, Pierre, additional, Redon, Richard, additional, Schluth-Bolard, Caroline, additional, Diguet, Flavie, additional, Rollat-Farnier, Pierre-Antoine, additional, Sanchez-Castro, Marta, additional, Vuillaume, Marie-Laure, additional, Sanlaville, Damien, additional, Duboule, Denis, additional, Mégarbané, André, additional, and Toutain, Annick, additional

Published
2019
Full Text
View/download PDF

22. Exome sequencing and pathogenicity-network analysis of five French families implicate mTOR signalling and autophagy in familial sarcoidosis

Author

Calender, Alain, primary, Lim, Clarice X., additional, Weichhart, Thomas, additional, Buisson, Adrien, additional, Besnard, Valérie, additional, Rollat-Farnier, Pierre Antoine, additional, Bardel, Claire, additional, Roy, Pascal, additional, Cottin, Vincent, additional, Devouassoux, Gilles, additional, Finat, Amélie, additional, Pinson, Stéphane, additional, Lebecque, Serge, additional, Nunes, Hilario, additional, Israel-Biet, Dominique, additional, Bentaher, Abderazzaq, additional, Valeyre, Dominique, additional, and Pacheco, Yves, additional

Published
2019
Full Text
View/download PDF

23. Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders

Author

Schluth-Bolard, Caroline, primary, Diguet, Flavie, additional, Chatron, Nicolas, additional, Rollat-Farnier, Pierre-Antoine, additional, Bardel, Claire, additional, Afenjar, Alexandra, additional, Amblard, Florence, additional, Amiel, Jeanne, additional, Blesson, Sophie, additional, Callier, Patrick, additional, Capri, Yline, additional, Collignon, Patrick, additional, Cordier, Marie-Pierre, additional, Coubes, Christine, additional, Demeer, Benedicte, additional, Chaussenot, Annabelle, additional, Demurger, Florence, additional, Devillard, Françoise, additional, Doco-Fenzy, Martine, additional, Dupont, Céline, additional, Dupont, Jean-Michel, additional, Dupuis-Girod, Sophie, additional, Faivre, Laurence, additional, Gilbert-Dussardier, Brigitte, additional, Guerrot, Anne-Marie, additional, Houlier, Marine, additional, Isidor, Bertrand, additional, Jaillard, Sylvie, additional, Joly-Hélas, Géraldine, additional, Kremer, Valérie, additional, Lacombe, Didier, additional, Le Caignec, Cédric, additional, Lebbar, Aziza, additional, Lebrun, Marine, additional, Lesca, Gaetan, additional, Lespinasse, James, additional, Levy, Jonathan, additional, Malan, Valérie, additional, Mathieu-Dramard, Michele, additional, Masson, Julie, additional, Masurel-Paulet, Alice, additional, Mignot, Cyril, additional, Missirian, Chantal, additional, Morice-Picard, Fanny, additional, Moutton, Sébastien, additional, Nadeau, Gwenaël, additional, Pebrel-Richard, Céline, additional, Odent, Sylvie, additional, Paquis-Flucklinger, Véronique, additional, Pasquier, Laurent, additional, Philip, Nicole, additional, Plutino, Morgane, additional, Pons, Linda, additional, Portnoï, Marie-France, additional, Prieur, Fabienne, additional, Puechberty, Jacques, additional, Putoux, Audrey, additional, Rio, Marlène, additional, Rooryck-Thambo, Caroline, additional, Rossi, Massimiliano, additional, Sarret, Catherine, additional, Satre, Véronique, additional, Siffroi, Jean-Pierre, additional, Till, Marianne, additional, Touraine, Renaud, additional, Toutain, Annick, additional, Toutain, Jérome, additional, Valence, Stéphanie, additional, Verloes, Alain, additional, Whalen, Sandra, additional, Edery, Patrick, additional, Tabet, Anne-Claude, additional, and Sanlaville, Damien, additional

Published
2019
Full Text
View/download PDF

24. Supravalvular Aortic Stenosis Caused by a Familial Chromosome 7 Inversion Disrupting the ELN Gene Uncovered by Whole-Genome Sequencing

Author

Pons, Linda, primary, Bouvagnet, Patrice, additional, Bakloul, Mohamed, additional, Di Filippo, Sylvie, additional, Buisson, Adrien, additional, Chatron, Nicolas, additional, Labalme, Audrey, additional, Metton, Olivier, additional, Mitchell, Julia, additional, Diguet, Flavie, additional, Rollat-Farnier, Pierre-Antoine, additional, Sanlaville, Damien, additional, and Schluth-Bolard, Caroline, additional

Published
2019
Full Text
View/download PDF

25. Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia.

Author

Rimbert, Antoine, Vanhoye, Xavier, Coulibaly, Dramane, Marrec, Marie, Pichelin, Matthieu, Charrière, Sybil, Peretti, Noël, Valéro, René, Wargny, Matthieu, Carrié, Alain, Lindenbaum, Pierre, Deleuze, Jean-François, Genin, Emmanuelle, Redon, Richard, Rollat-Farnier, Pierre Antoine, Goxe, Didier, Degraef, Gilles, Marmontel, Oriane, Divry, Eléonore, and Bigot-Corbel, Edith

Published
2021
Full Text
View/download PDF

26. Whole MYBPC3 NGS sequencing as a molecular strategy to improve the efficiency of molecular diagnosis of patients with hypertrophic cardiomyopathy.

Author

Janin, Alexandre, Chanavat, Valérie, Rollat‐Farnier, Pierre‐Antoine, Bardel, Claire, Nguyen, Karine, Chevalier, Philippe, Eicher, Jean‐Christophe, Faivre, Laurence, Piard, Juliette, Albert, Emma, Nony, Severine, and Millat, Gilles

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, historically believed to affect 1 of 500 people. MYBPC3 pathogenic variations are the most frequent cause of familial HCM and more than 90% of them introduce a premature termination codon. The current study aims to determine the prevalence of deep intronic MYBPC3 pathogenic variations that could lead to splice mutations. To improve molecular diagnosis, a next‐generation sequencing (NGS) workflow based on whole MYBPC3 sequencing of a cohort of 93 HCM patients, for whom no putatively causative point mutations were identified after NGS sequencing of a panel of 48 cardiomyopathy‐causing genes, was performed. Our approach led us to reconsider the molecular diagnosis of six patients of the cohort (6.5%). These HCM probands were carriers of either a new large MYBPC3 rearrangement or splice intronic variations (five cases). Four pathogenic intronic variations, including three novel ones, were detected. Among them, the prevalence of one of them (NM_000256.3:c.1927+ 600 C>T) was estimated at about 0.35% by the screening of 1,040 unrelated HCM individuals. This study suggests that deep MYBPC3 splice mutations account for a significant proportion of HCM cases (6.5% of this cohort). Consequently, NGS sequencing of MYBPC3 intronic sequences have to be performed systematically. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

27. Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXDgene cluster

Author

Le Caignec, Cédric, Pichon, Olivier, Briand, Annaig, de Courtivron, Benoît, Bonnard, Christian, Lindenbaum, Pierre, Redon, Richard, Schluth-Bolard, Caroline, Diguet, Flavie, Rollat-Farnier, Pierre-Antoine, Sanchez-Castro, Marta, Vuillaume, Marie-Laure, Sanlaville, Damien, Duboule, Denis, Mégarbané, André, and Toutain, Annick

Abstract

The HoxDcluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the transcription of HoxDgenes. In rare patients, duplications, balanced translocations or inversions misregulating HOXDgenes are responsible for mesomelic dysplasia of the upper and lower limbs. By aCGH, whole-genome mate-pair sequencing, long-range PCR and fiber fluorescent in situ hybridization, we studied patients from two families displaying mesomelic dysplasia limited to the upper limbs. We identified microduplications including the HOXDcluster and showed that microduplications were in an inverted orientation and inserted between the HOXDcluster and the telomeric enhancers. Our results highlight the existence of an autosomal dominant condition consisting of isolated ulnar dysplasia caused by microduplications inserted between the HOXDcluster and the telomeric enhancers. The duplications likely disconnect the HOXD9to HOXD11genes from their regulatory sequences. This presumptive loss-of-function may have contributed to the phenotype. In both cases, however, these rearrangements brought HOXD13closer to telomeric enhancers, suggesting that the alterations derive from the dominant-negative effect of this digit-specific protein when ectopically expressed during the early development of forearms, through the disruption of topologically associating domain structure at the HOXDlocus.

Published
2020
Full Text
View/download PDF

28. Two Host Clades, Two Bacterial Arsenals: Evolution through Gene Losses in Facultative Endosymbionts

Author

Rollat-Farnier, Pierre-Antoine, Santos-Garcia, Diego, Rao, Qiong, Sagot, Marie-France, Silva, Francisco J, Henri, Hélène, Zchori-Fein, Einat, Latorre, Amparo, Moya, Andrés, Barbe, Valérie, Liu, Shu-Sheng, Wang, Xiao-Wei, Vavre, Fabrice, Mouton, Laurence, Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut Cavanilles de Biodiversitat i Biologia Evolutiva (ICBiBE), Universitat de València (UV), Zhejiang Agriculture and Forestry University, Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Agricultural Research Organisation (ARO), Volcani Center, Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique et évolution des interactions hôtes-parasites, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), and European Project: 247073,EC:FP7:ERC,ERC-2009-AdG,SISYPHE(2010)

Subjects
Hamiltonella defensa, Virulence Factors, [SDV]Life Sciences [q-bio], fungi, food and beverages, Genomics, comparative genomics, biochemical phenomena, metabolism, and nutrition, Bemisia tabaci, Evolution, Molecular, Hemiptera, aphids, Enterobacteriaceae, Cell Wall, Animals, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Symbiosis, Gene Deletion, Genome, Bacterial, Phylogeny, Research Article
Abstract

International audience; Bacterial endosymbiosis is an important evolutionary process in insects, which can harbor both obligate and facultative symbionts. The evolution of these symbionts is driven by evolutionary convergence, and they exhibit among the tiniest genomes in prokaryotes. The large host spectrum of facultative symbionts and the high diversity of strategies they use to infect new hosts probably impact the evolution of their genome and explain why they undergo less severe genomic erosion than obligate symbionts. Candidatus Hamiltonella defensa is suitable for the investigation of the genomic evolution of facultative symbionts because the bacteria are engaged in specific relationships in two clades of insects. In aphids, H. defensa is found in several species with an intermediate prevalence and confers protection against parasitoids. In whiteflies, H. defensa is almost fixed in some species of Bemisia tabaci, which suggests an important role of and a transition toward obligate symbiosis. In this study, comparisons of the genome of H. defensa present in two B. tabaci species (Middle East Asia Minor 1 and Mediterranean) and in the aphid Acyrthosiphon pisum revealed that they belong to two distinct clades and underwent specific gene losses. In aphids, it contains highly virulent factors that could allow protection and horizontal transfers. In whiteflies, the genome lost these factors and seems to have a limited ability to acquire genes. However it contains genes that could be involved in the production of essential nutrients, which is consistent with a primordial role for this symbiont. In conclusion, although both lineages of H. defensa have mutualistic interactions with their hosts, their genomes follow distinct evolutionary trajectories that reflect their phenotype and could have important consequences on their evolvability.

Published
2015
Full Text
View/download PDF

29. Evolution of the genomes of the endosymbionts in phloem-sap feeding insects: the case of Hamiltonella defensa interacting with its various partners

Author

Rollat-Farnier, Pierre-Antoine, Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard - Lyon I, Marie-France Sagot, Laurence Mouton, Fabrice Vavre, An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1, and European Project: 247073,EC:FP7:ERC,ERC-2009-AdG,SISYPHE(2010)

Subjects
Hamiltonella defensa, Endosymbiont ecology, Génomique comparative, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Comparative genomics, Genomic evolution, Écologie des endosymbiotes, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Ecology of endosymbionts, Évolution génomique
Abstract

Insect cells host many endosymbiotic bacteria, which are in general classified according to their importance for the host: "primary" symbionts are by definition mandatory and synthesize essential nutrients for the insects that feed on poor or unbalanced food sources, while "secondary" symbionts are optional and use mutualistic strategies and/or manipulation of reproduction to invade and persist within insect populations.Hamiltonella defensa is a secondary endosymbiont that established two distinct associations with phloemophagous insects. In aphids, it protects the host against parasitoid attacks. Its ability to infect many host tissues, notably the hemolymph, could promote its contact with parasitoid eggs. Despite this protective phenotype, the high costs associated with its presence within the host prevent its fixation in the population. In the whitefly Bemisia tabaci however, this symbiont is found only in cells specialized in hosting endosymbionts, the bacteriocytes. In these cells, it cohabits with other symbiotic species, such as the primary symbiont Portiera aleyrodidarum, a proximity that favors potential exchanges between the two symbionts. It is fixed in populations of B. tabaci, which suggests an important role for the consortium, probably nutritious.As part of this PhD thesis, we studied the specificities of each of these systems. First, in the bacteriocytes of B. tabaci, we identified a partitioning of the synthetic capacities of two endosymbionts, H. defensa and P. aleyrodidarum, in addition to a potential metabolic complementation between the symbionts and their host for the synthesis of essential amino acids. We proposed a key nutritive role for H. defensa, which would indicate a transition to a mandatory status in relation to the host and would explain its fixation in the population.We also focused on the genomic evolution of the genus Hamiltonella, by comparing the strains infecting B. tabaci with a strain infecting the aphids. We highlighted the specialization of the symbionts to their hosts, and found that the genomes of the endosymbionts reflected their respective ecology. The aphid strain thus possesses many virulence factors and is associated with two partners, a bacteriophage and a recombination plasmid. These systems, inactive in the symbiont of B. tabaci, are directly related to the protection against and arms race with parasitoids. Conversely, the presumed avirulence of whitefly endosymbionts is consistent with their nutritional phenotype and a transition to a mandatory status to the host.Finally, we studied the phenomenon of ‘accelerated mutation rate’ in H. defensa, compared to its sister species Regiella insecticola, which is also a clade of protective endosymbionts of aphids. After excluding the assumption that the transition to the intracellular life occurred independently in the two lineages, we tried to establish a link between these differences in terms of evolvability in the endosymbionts and of their gene contents, particularly for genes involved in ecology and DNA repair.All the results obtained during this PhD have provided insight into the evolution of the species H. defensa, since the last ancestor to; Les cellules des insectes hébergent de nombreuses bactéries endosymbiotiques, que l’on catégorise généralement selon leur importance pour l’hôte : les symbiotes dits « primaires » sont par définition obligatoires, et synthétisent des nutriments essentiels pour les insectes se nourrissant d’aliments pauvres ou déséquilibrés ; les symbiotes dits « secondaires » sont facultatifs, et utilisent des stratégies mutualistes et/ou la manipulation de la reproduction pour envahir et se maintenir dans les populations d’insectes.Hamiltonella defensa est un endosymbiote secondaire ayant établi deux associations très distinctes chez les insectes phloémophages. Chez les pucerons, la bactérie protège l’hôte contre les parasitoïdes. Elle infecte de nombreux tissus dans l’hôte, et notamment l’hémolymphe, ce qui favoriserait le contact avec les oeufs de parasitoïdes. Malgré ce phénotype protecteur, les coûts importants que sa présence inflige à son hôte empêchent sa fixation dans les populations. Chez l’aleurode Bemisia tabaci, on ne retrouve la bactérie que dans des cellules spécialisées dans l’hébergement des endosymbiotes, les bactériocytes. Elle s’y trouve entre autres en présence du symbiote primaire, Portiera aleyrodidarum, des conditions de vie propices aux échanges entre les deux symbiotes. Elle est fixée dans les populations d’insectes, ce qui suggère un rôle important pour le consortium, qui serait nutritif.Dans le cadre de cette thèse, nous nous sommes intéressés aux spécificités de chacun de ces systèmes. Tout d’abord, au sein des bactériocytes de B. tabaci, nous avons révélé un partitionnement des capacités synthétiques des deux endosymbiotes H. defensa et P. aleyrodidarum, assorti à de potentielles complémentations métaboliques entre eux et avec leur hôte pour la synthèse d’acides aminés essentiels. Nous avons proposé un rôle nutritif primordial pour H. defensa, qui traduirait une transition vers un statut obligatoire pour l’hôte et justifierait sa fixation dans les populations.Nous nous sommes également attardés sur l’évolution génomique du genre Hamiltonella, en comparant des souches infectant B. tabaci à une souche de puceron. Nous avons mis en évidence la spécialisation des symbiotes à leur hôte, et révélé que les génomes des endosymbiotes faisaient écho à leur écologie respective. La souche du puceron possède ainsi de nombreux facteurs de virulence et est associée à deux partenaires, un bactériophage et un plasmide de recombinaison. Ces systèmes, inactifs chez le symbiote de B. tabaci, sont directement en lien avec la protection et la course aux armements engagés contre les parasitoïdes. À l’inverse, l’avirulence présumée des symbiotes de l’aleurode est cohérente avec leur phénotype nutritif et une transition vers un statut obligatoire pour l’hôte.Pour finir, nous nous sommes intéressés aux phénomènes d’accélération des taux de mutations chez H. defensa, comparativement à son espèce-soeur Regiella insecticola, également endosymbiotique et protectrice du puceron. Après avoir éliminé l’hypothèse selon laquelle la transition vers la vie intracellulaire aurait eu lieu indépendamment dans les deux lignées, nous avons tenté d’établir un lien entre ces différentiels d’évolvabilité chez les endosymbiotes et leur contenu en gènes, notamment ceux impliqués dans l’écologie et la réparation de l’ADN.L’ensemble des résultats obtenus au cours de ce Doctorat ont permis de mieux comprendre l’évolution de l’espèce H. defensa, depuis le dernier ancêtre jusqu’aux espèces actuelles, en tâchant de faire le lien entre phénotype de la bactérie et évolution génomique.

Published
2014

30. Évolution des génomes des endosymbiotes chez les insectes phloémophages : le cas d'Hamiltonella defensa en interaction avec ses différents partenaires

Author

Rollat-Farnier, Pierre-Antoine, Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard - Lyon I, Marie-France Sagot, Laurence Mouton, and Fabrice Vavre

Subjects
Hamiltonella defensa, Endosymbiont ecology, Génomique comparative, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Comparative genomics, Genomic evolution, Écologie des endosymbiotes, Évolution génomique
Abstract

Hamiltonella defensa is a secondary endosymbiont that established two distinct associations with phloemophagous insects. In aphids, it protects the host against parasitoid attacks. Its ability to infect many host tissues, notably the hemolymph, could promote its contact with parasitoid eggs. Despite this protective phenotype, the high costs associated with its presence within the host prevent its fixation in the population. In the whitefly Bemisia tabaci however, this symbiont is found only in cells specialized in hosting endosymbionts, the bacteriocytes. In these cells, it cohabits with other symbiotic species, such as the primary symbiont Portiera aleyrodidarum, a proximity that favors potential exchanges between the two symbionts. It is fixed in populations of B. tabaci, which suggests an important role for the consortium, probably nutritious. As part of this PhD thesis, we studied the specificities of each of these systems. We also focused on the genomic evolution of the genus Hamiltonella, by comparing the strains infecting B. tabaci with a strain infecting the aphids. Finally, we studied the phenomenon of ‘accelerated mutation rate’ in H. defensa, compared to its sister species Regiella insecticola, which is also a clade of protective endosymbionts of aphids. After excluding the assumption that the transition to the intracellular life occurred independently in the two lineages, we tried to establish a link between these differences in terms of evolvability in the endosymbionts and of their gene contents, particularly for genes involved in ecology and DNA repair. All the results obtained during this PhD have provided insight into the evolution of the species H. defensa, since the last ancestor to the present species, by establishing a link between bacterial phenotype and genomic evolution; Hamiltonella defensa est un endosymbiote secondaire ayant établi deux associations très distinctes chez les insectes phloémophages. Chez les pucerons, la bactérie protège l'hôte contre les parasitoïdes. Elle infecte de nombreux tissus dans l'hôte, et notamment l'hémolymphe, ce qui favoriserait le contact avec les oeufs de parasitoïdes. Malgré ce phénotype protecteur, les coûts importants que sa présence inflige à son hôte empêchent sa fixation dans les populations. Chez l'aleurode Bemisia tabaci, on ne retrouve la bactérie que dans des cellules spécialisées dans l'hébergement des endosymbiotes, les bactériocytes. Elle s'y trouve entre autres en présence du symbiote primaire, Portiera aleyrodidarum, des conditions de vie propices aux échanges entre les deux symbiotes. Elle est fixée dans les populations d'insectes, ce qui suggère un rôle important pour le consortium, qui serait nutritif. Dans le cadre de cette thèse, nous nous sommes intéressés aux spécificités de chacun de ces systèmes. Nous nous sommes également attardés sur l'évolution génomique du genre Hamiltonella, en comparant des souches infectant B. tabaci à une souche de puceron. Pour finir, nous nous sommes intéressés aux phénomènes d'accélération des taux de mutations chez H. defensa, comparativement à son espèce-soeur Regiella insecticola, également endosymbiotique et protectrice du puceron. Après avoir éliminé l'hypothèse selon laquelle la transition vers la vie intracellulaire aurait eu lieu indépendamment dans les deux lignées, nous avons tenté d'établir un lien entre ces différentiels d'évolvabilité chez les endosymbiotes et leur contenu en gènes, notamment ceux impliqués dans l'écologie et la réparation de l'ADN. L'ensemble des résultats obtenus au cours de ce Doctorat ont permis de mieux comprendre l'évolution de l'espèce H. defensa, depuis le dernier ancêtre jusqu'aux espèces actuelles, en tâchant de faire le lien entre phénotype de la bactérie et évolution génomique

Published
2014

31. Supravalvular Aortic Stenosis Caused by a Familial Chromosome 7 Inversion Disrupting the ELNGene Uncovered by Whole-Genome Sequencing

Author

Pons, Linda, Bouvagnet, Patrice, Bakloul, Mohamed, Di Filippo, Sylvie, Buisson, Adrien, Chatron, Nicolas, Labalme, Audrey, Metton, Olivier, Mitchell, Julia, Diguet, Flavie, Rollat-Farnier, Pierre-Antoine, Sanlaville, Damien, and Schluth-Bolard, Caroline

Abstract

Apparently, balanced chromosomal rearrangements usually have no phenotypic consequences for the carrier. However, in some cases, they may be associated with an abnormal phenotype. We report herein the case of a 4-year-old boy presenting with clinically isolated supravalvular aortic stenosis (SVAS). No chromosomal imbalance was detected by array CGH. The karyotype showed a balanced paracentric chromosome 7 inversion. Breakpoint characterization using paired-end whole-genome sequencing (WGS) revealed an ELN gene disruption in intron 1, accounting for the phenotype. Family study showed that the inversion was inherited, with incomplete penetrance. To our knowledge, this is the first case of a disruption of the ELNgene characterized by WGS. It contributes to refine the genotype-phenotype correlation in ELNdisruption. Although this disruption is a rare etiology of SVAS, it cannot be detected by the diagnostic tests usually performed, such as array CGH or sequencing methods (Sanger, panel, or exome sequencing). With the future perspective of WGS as a diagnostic tool, it will be important to include a structural variation analysis in order to detect balanced rearrangements and gene disruption.

Published
2019
Full Text
View/download PDF

32. Genome reduction and potential metabolic complementation of the dual endosymbionts in the whitefly Bemisia tabaci

Author

Rao, Qiong, primary, Rollat-Farnier, Pierre-Antoine, additional, Zhu, Dan-Tong, additional, Santos-Garcia, Diego, additional, Silva, Francisco J, additional, Moya, Andrés, additional, Latorre, Amparo, additional, Klein, Cecilia C, additional, Vavre, Fabrice, additional, Sagot, Marie-France, additional, Liu, Shu-Sheng, additional, Mouton, Laurence, additional, and Wang, Xiao-Wei, additional

Published
2015
Full Text
View/download PDF

34. Genome reduction and potential metabolic complementation of the dual endosymbionts in the whitefly Bemisia tabaci.

Author

Qiong Rao, Rollat-Farnier, Pierre-Antoine, Dan-Tong Zhu, Santos-Garcia, Diego, Silva, Francisco J., Moya, Andrés, Latorre, Amparo, Klein, Cecilia C., Vavre, Fabrice, Sagot, Marie-France, Shu-Sheng Liu, Mouton, Laurence, and Xiao-Wei Wang

Subjects
*SWEETPOTATO whitefly, *ENTEROBACTERIACEAE, *CANDIDATUS, *INVERTEBRATE-bacteria relationships, *ENDOSYMBIOSIS
Abstract

Background: The whitefly Bemisia tabaci is an important agricultural pest with global distribution. This phloem-sap feeder harbors a primary symbiont, "Candidatus Portiera aleyrodidarum", which compensates for the deficient nutritional composition of its food sources, and a variety of secondary symbionts. Interestingly, all of these secondary symbionts are found in co-localization with the primary symbiont within the same bacteriocytes, which should favor the evolution of strong interactions between symbionts. Results: In this paper, we analyzed the genome sequences ofthe primary symbiont Portiera and ofthe secondary symbiont Hamiltonella in the B. tabaci Mediterranean (MED) species in order to gain insight into the metabolic role of each symbiont in the biology of their host. The genome sequences of the uncultured symbionts Portiera and Hamiltonella were obtained from one single bacteriocyte of MED B. tabaci. As already reported, the genome of Portiera is highly reduced (357 kb), but has kept a number of genes encoding most essential amino-acids and carotenoids. On the other hand, Portiera lacks almost all the genes involved in the synthesis of vitamins and cofactors. Moreover, some pathways are incomplete, notably those involved in the synthesis of some essential amino-acids. Interestingly, the genome of Hamiltonella revealed that this secondary symbiont can not only provide vitamins and cofactors, but also complete the missing steps of some of the pathways of Portiera. In addition, some critical amino-acid biosynthetic genes are missing in the two symbiotic genomes, but analysis of whitefly transcriptome suggests that the missing steps may be performed by the whitefly itself or its microbiota. Conclusions: These data suggest that Portiera and Hamiltonella are not only complementary but could also be mutually dependent to provide a full complement of nutrients to their host. Altogether, these results illustrate how functional redundancies can lead to gene losses in the genomes ofthe different symbiotic partners, reinforcing their inter-dependency. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

35. Genome sequencing in cytogenetics: Comparison of short-read and linked-read approaches for germline structural variant detection and characterization.

Author

Uguen K, Jubin C, Duffourd Y, Bardel C, Malan V, Dupont JM, El Khattabi L, Chatron N, Vitobello A, Rollat-Farnier PA, Baulard C, Lelorch M, Leduc A, Tisserant E, Tran Mau-Them F, Danjean V, Delepine M, Till M, Meyer V, Lyonnet S, Mosca-Boidron AL, Thevenon J, Faivre L, Thauvin-Robinet C, Schluth-Bolard C, Boland A, Olaso R, Callier P, Romana S, Deleuze JF, and Sanlaville D

Subjects
Abnormalities, Multiple diagnosis, Abnormalities, Multiple genetics, Chromosome Disorders diagnosis, Germ-Line Mutation, Humans, Intellectual Disability diagnosis, Intellectual Disability genetics, Chromosome Disorders genetics, Cytogenetics methods, Genetic Testing methods, Genomic Structural Variation, Whole Genome Sequencing methods
Abstract

Background: Structural variants (SVs) include copy number variants (CNVs) and apparently balanced chromosomal rearrangements (ABCRs). Genome sequencing (GS) enables SV detection at base-pair resolution, but the use of short-read sequencing is limited by repetitive sequences, and long-read approaches are not yet validated for diagnosis. Recently, 10X Genomics proposed Chromium, a technology providing linked-reads to reconstruct long DNA fragments and which could represent a good alternative. No study has compared short-read to linked-read technologies to detect SVs in a constitutional diagnostic setting yet. The aim of this work was to determine whether the 10X Genomics technology enables better detection and comprehension of SVs than short-read WGS., Methods: We included 13 patients carrying various SVs. Whole genome analyses were performed using paired-end HiSeq X sequencing with (linked-read strategy) or without (short-read strategy) Chromium library preparation. Two different bioinformatic pipelines were used: Variants are called using BreakDancer for short-read strategy and LongRanger for long-read strategy. Variant interpretations were first blinded., Results: The short-read strategy allowed diagnosis of known SV in 10/13 patients. After unblinding, the linked-read strategy identified 10/13 SVs, including one (patient 7) missed by the short-read strategy., Conclusion: In conclusion, regarding the results of this study, 10X Genomics solution did not improve the detection and characterization of SV., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Published
2020
Full Text
View/download PDF

36. Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster.

Author

Le Caignec C, Pichon O, Briand A, de Courtivron B, Bonnard C, Lindenbaum P, Redon R, Schluth-Bolard C, Diguet F, Rollat-Farnier PA, Sanchez-Castro M, Vuillaume ML, Sanlaville D, Duboule D, Mégarbané A, and Toutain A

Subjects
Bone Diseases, Developmental pathology, Cells, Cultured, Female, Humans, Infant, Loss of Function Mutation, Male, Multigene Family, Phenotype, Upper Extremity Deformities, Congenital pathology, Bone Diseases, Developmental genetics, Gene Duplication, Homeodomain Proteins genetics, Upper Extremity Deformities, Congenital genetics
Abstract

The HoxD cluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the transcription of HoxD genes. In rare patients, duplications, balanced translocations or inversions misregulating HOXD genes are responsible for mesomelic dysplasia of the upper and lower limbs. By aCGH, whole-genome mate-pair sequencing, long-range PCR and fiber fluorescent in situ hybridization, we studied patients from two families displaying mesomelic dysplasia limited to the upper limbs. We identified microduplications including the HOXD cluster and showed that microduplications were in an inverted orientation and inserted between the HOXD cluster and the telomeric enhancers. Our results highlight the existence of an autosomal dominant condition consisting of isolated ulnar dysplasia caused by microduplications inserted between the HOXD cluster and the telomeric enhancers. The duplications likely disconnect the HOXD9 to HOXD11 genes from their regulatory sequences. This presumptive loss-of-function may have contributed to the phenotype. In both cases, however, these rearrangements brought HOXD13 closer to telomeric enhancers, suggesting that the alterations derive from the dominant-negative effect of this digit-specific protein when ectopically expressed during the early development of forearms, through the disruption of topologically associating domain structure at the HOXD locus.

Published
2020
Full Text
View/download PDF

37. Identification of mobile retrocopies during genetic testing: Consequences for routine diagnosis.

Author

Chatron N, Cassinari K, Quenez O, Baert-Desurmont S, Bardel C, Buisine MP, Calpena E, Capri Y, Corominas Galbany J, Diguet F, Edery P, Isidor B, Labalme A, Le Caignec C, Lévy J, Lecoquierre F, Lindenbaum P, Pichon O, Rollat-Farnier PA, Simonet T, Saugier-Veber P, Tabet AC, Toutain A, Wilkie AOM, Lesca G, Sanlaville D, Nicolas G, and Schluth-Bolard C

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Diagnostic Tests, Routine, Female, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Middle Aged, Young Adult, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Testing, Retroelements
Abstract

Human retrocopies, that is messenger RNA transcripts benefitting from the long interspersed element 1 machinery for retrotransposition, may have specific consequences for genomic testing. Next genetration sequencing (NGS) techniques allow the detection of such mobile elements but they may be misinterpreted as genomic duplications or be totally overlooked. We report eight observations of retrocopies detected during diagnostic NGS analyses of targeted gene panels, exome, or genome sequencing. For seven cases, while an exons-only copy number gain was called, read alignment inspection revealed a depth of coverage shift at every exon-intron junction where indels were also systematically called. Moreover, aberrant chimeric read pairs spanned entire introns or were paired with another locus for terminal exons. The 8th retrocopy was present in the reference genome and thus showed a normal NGS profile. We emphasize the existence of retrocopies and strategies to accurately detect them at a glance during genetic testing and discuss pitfalls for genetic testing., (© 2019 Wiley Periodicals, Inc.)

Published
2019
Full Text
View/download PDF

38. Two host clades, two bacterial arsenals: evolution through gene losses in facultative endosymbionts.

Author

Rollat-Farnier PA, Santos-Garcia D, Rao Q, Sagot MF, Silva FJ, Henri H, Zchori-Fein E, Latorre A, Moya A, Barbe V, Liu SS, Wang XW, Vavre F, and Mouton L

Subjects
Animals, Cell Wall chemistry, Enterobacteriaceae classification, Enterobacteriaceae metabolism, Enterobacteriaceae pathogenicity, Genome, Bacterial, Genomics, Phylogeny, Virulence Factors genetics, Aphids microbiology, Enterobacteriaceae genetics, Evolution, Molecular, Gene Deletion, Hemiptera microbiology, Symbiosis
Abstract

Bacterial endosymbiosis is an important evolutionary process in insects, which can harbor both obligate and facultative symbionts. The evolution of these symbionts is driven by evolutionary convergence, and they exhibit among the tiniest genomes in prokaryotes. The large host spectrum of facultative symbionts and the high diversity of strategies they use to infect new hosts probably impact the evolution of their genome and explain why they undergo less severe genomic erosion than obligate symbionts. Candidatus Hamiltonella defensa is suitable for the investigation of the genomic evolution of facultative symbionts because the bacteria are engaged in specific relationships in two clades of insects. In aphids, H. defensa is found in several species with an intermediate prevalence and confers protection against parasitoids. In whiteflies, H. defensa is almost fixed in some species of Bemisia tabaci, which suggests an important role of and a transition toward obligate symbiosis. In this study, comparisons of the genome of H. defensa present in two B. tabaci species (Middle East Asia Minor 1 and Mediterranean) and in the aphid Acyrthosiphon pisum revealed that they belong to two distinct clades and underwent specific gene losses. In aphids, it contains highly virulent factors that could allow protection and horizontal transfers. In whiteflies, the genome lost these factors and seems to have a limited ability to acquire genes. However it contains genes that could be involved in the production of essential nutrients, which is consistent with a primordial role for this symbiont. In conclusion, although both lineages of H. defensa have mutualistic interactions with their hosts, their genomes follow distinct evolutionary trajectories that reflect their phenotype and could have important consequences on their evolvability., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results