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1. DNA methylation-based profiling of horse archaeological remains for age-at-death and castration

Author

Xuexue Liu, Andaine Seguin-Orlando, Lorelei Chauvey, Gaëtan Tressières, Stéphanie Schiavinato, Laure Tonasso-Calvière, Jean-Marc Aury, Aude Perdereau, Stefanie Wagner, Pierre Clavel, Oscar Estrada, Jianfei Pan, Yuehui Ma, Jacob Enk, Alison Devault, Jennifer Klunk, Sébastien Lepetz, Benoit Clavel, Lin Jiang, Patrick Wincker, Yvette Running Horse Collin, Clio Der Sarkissian, and Ludovic Orlando

Subjects
Molecular genetics, Science
Abstract

Summary: Age profiling of archaeological bone assemblages can inform on past animal management practices, but is limited by the fragmentary nature of the fossil record and the lack of universal skeletal markers for age. DNA methylation clocks offer new, albeit challenging, alternatives for estimating the age-at-death of ancient individuals. Here, we take advantage of the availability of a DNA methylation clock based on 31,836 CpG sites and dental age markers in horses to assess age predictions in 84 ancient remains. We evaluate our approach using whole-genome sequencing data and develop a capture assay providing reliable estimates for only a fraction of the cost. We also leverage DNA methylation patterns to assess castration practice in the past. Our work opens for a deeper characterization of past husbandry and ritual practices and holds the potential to reveal age mortality profiles in ancient societies, once extended to human remains.

Published
2023
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2. CASCADE: A Custom-Made Archiving System for the Conservation of Ancient DNA Experimental Data

Author

Dirk Dolle, Antoine Fages, Xavier Mata, Stéphanie Schiavinato, Laure Tonasso-Calvière, Lorelei Chauvey, Stefanie Wagner, Clio Der Sarkissian, Aurore Fromentier, Andaine Seguin-Orlando, and Ludovic Orlando

Subjects
ancient DNA, laboratory management, database, LIMS, traceability, conservation, Evolution, QH359-425, Ecology, QH540-549.5
Abstract

The field of ancient genomics has undergone a true revolution during the last decade. Input material, time requirements and processing costs have first limited the number of specimens amenable to genome sequencing. However, the discovery that archeological material such as petrosal bones can show increased ancient DNA preservation rates, combined with advances in sequencing technologies, molecular methods for the recovery of degraded DNA fragments and bioinformatics, has vastly expanded the range of samples compatible with genome-wide investigation. Experimental procedures for DNA extraction, genomic library preparation and target enrichment have become more streamlined, and now also include automation. These procedures have considerably reduced the amount of work necessary for data generation, effectively adapting the processing capacity of individual laboratories to the increasing numbers of analyzable samples. Handling vast amounts of samples, however, comes with logistical challenges. Laboratory capacities, equipment, and people need to be efficiently coordinated, and the progress of each sample through the different experimental stages needs to be fully traceable, especially as archeological remains of animals or plants are often provided and/or handled by many different collaborators. Here we present CASCADE, a laboratory information management system (LIMS) dealing with the specificities of ancient DNA sample processing and tracking, applicable by large and small laboratories alike, and scalable to large projects involving the analysis of thousands of samples and more. By giving an account of the specimen’s progress at any given analytical step, CASCADE not only optimizes the collaborative experience, including real-time information sharing with third parties, but also improves the efficacy of data generation and traceability in-house.

Published
2020
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3. Oral health status in historic population: Macroscopic and metagenomic evidence.

Author

Claire Willmann, Xavier Mata, Kristian Hanghoej, Laure Tonasso, Lenka Tisseyre, Céline Jeziorski, Elodie Cabot, Pierre Chevet, Eric Crubézy, Ludovic Orlando, Rémi Esclassan, and Catherine Thèves

Subjects
Medicine, Science
Abstract

Recent developments in High-Throughput DNA sequencing (HTS) technologies and ancient DNA (aDNA) research have opened access to the characterization of the microbial communities within past populations. Most studies have, however, relied on the analysis of dental calculus as one particular material type particularly prone to the molecular preservation of ancient microbial biofilms and potential of entire teeth for microbial characterization, both of healthy communities and pathogens in ancient individuals, remains overlooked. In this study, we used shotgun sequencing to characterize the bacterial composition from historical subjects showing macroscopic evidence of oral pathologies. We first carried out a macroscopic analysis aimed at identifying carious or periodontal diseases in subjects belonging to a French rural population of the 18th century AD. We next examined radiographically six subjects showing specific, characteristic dental pathologies and applied HTS shotgun sequencing to characterize the microbial communities present in and on the dental material. The presence of Streptococcus mutans and also Rothia dentocariosa, Actinomyces viscosus, Porphyromonas gingivalis, Tannerella forsythia, Pseudoramibacter alactolyticus, Olsenella uli and Parvimonas micra was confirmed through the presence of typical signatures of post-mortem DNA damage at an average depth-of-coverage ranging from 0.5 to 7X, with a minimum of 35% (from 35 to 93%) of the positions in the genome covered at least once. Each sampled tooth showed a specific bacterial signature associated with carious or periodontal pathologies. This work demonstrates that from a healthy independent tooth, without visible macroscopic pathology, we can identify a signature of specific pathogens and deduce the oral health status of an individual.

Published
2018
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4. Tracing Arab-Islamic inheritance in Madagascar: study of the Y-chromosome and mitochondrial DNA in the Antemoro.

Author

Mélanie Capredon, Nicolas Brucato, Laure Tonasso, Valérie Choesmel-Cadamuro, François-Xavier Ricaut, Harilanto Razafindrazaka, Andriamihaja Bakomalala Rakotondrabe, Mamisoa Adelta Ratolojanahary, Louis-Paul Randriamarolaza, Bernard Champion, and Jean-Michel Dugoujon

Subjects
Medicine, Science
Abstract

Madagascar is located at the crossroads of the Asian and African worlds and is therefore of particular interest for studies on human population migration. Within the large human diversity of the Great Island, we focused our study on a particular ethnic group, the Antemoro. Their culture presents an important Arab-Islamic influence, but the question of an Arab biological inheritance remains unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this ethnic group. Although the majority of Antemoro genetic ancestry comes from sub-Saharan African and Southeast Asian gene pools, we observed in their paternal lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins. This inheritance was restricted to some Antemoro sub-groups. Statistical analyses tended to confirm significant Middle Eastern genetic contribution. This study gives a new perspective to the large human genetic diversity in Madagascar.

Published
2013
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5. The genomic history and global expansion of domestic donkeys

Author

Evelyn T. Todd, Laure Tonasso-Calvière, Loreleï Chauvey, Stéphanie Schiavinato, Antoine Fages, Andaine Seguin-Orlando, Pierre Clavel, Naveed Khan, Lucía Pérez Pardal, Laura Patterson Rosa, Pablo Librado, Harald Ringbauer, Marta Verdugo, John Southon, Jean-Marc Aury, Aude Perdereau, Emmanuelle Vila, Matilde Marzullo, Ornella Prato, Umberto Tecchiati, Giovanna Bagnasco Gianni, Antonio Tagliacozzo, Vincenzo Tinè, Francesca Alhaique, João Luís Cardoso, Maria João Valente, Miguel Telles Antunes, Laurent Frantz, Beth Shapiro, Daniel G. Bradley, Nicolas Boulbes, Armelle Gardeisen, Liora Kolska Horwitz, Aliye Öztan, Benjamin S. Arbuckle, Vedat Onar, Benoît Clavel, Sébastien Lepetz, Ali Akbar Vahdati, Hossein Davoudi, Azadeh Mohaseb, Marjan Mashkour, Olivier Bouchez, Cécile Donnadieu, Patrick Wincker, Samantha A. Brooks, Albano Beja-Pereira, Dong-Dong Wu, and Ludovic Orlando

Subjects
Ancestry, Multidisciplinary, Asia, Genome, DNA, Equidae, Genomics, Insights, Gene flow, Domestication, Africa, Animals, Humans, Equids, Phylogeny
Abstract

Donkeys transformed human history as essential beasts of burden for long-distance movement, especially across semi-arid and upland environments. They remain insufficiently studied despite globally expanding and providing key support to low- to middle-income communities. To elucidate their domestication history, we constructed a comprehensive genome panel of 207 modern and 31 ancient donkeys, as well as 15 wild equids. We found a strong phylogeographic structure in modern donkeys that supports a single domestication in Africa similar to 5000 BCE, followed by further expansions in this continent and Eurasia and ultimately returning to Africa. We uncover a previously unknown genetic lineage in the Levant similar to 200 BCE, which contributed increasing ancestry toward Asia. Donkey management involved inbreeding and the production of giant bloodlines at a time when mules were essential to the Roman economy and military. French National Research Agency (ANR) ANR-10-INBS-09 info:eu-repo/semantics/publishedVersion

Published
2022

7. Performance and automation of ancient DNA capture with RNA hyRAD probes

Author

Stéphanie Schiavinato, Tomasz Suchan, Alexander J.E. Pryor, Keiko Kitagawa, Alexander Bessudnov, Naveed Khan, Marek Nowak, Alan K. Outram, Silvia Valenzuela-Lamas, Johannes Krause, Mariya A. Kusliy, Laure Tonasso-Calvière, Alexander A. Bessudnov, Sylwia Pospuła, Marcel Keller, Alexey A. Tishkin, Lorelei Chauvey, John Southon, Alexander S. Graphodatsky, Krzysztof Tunia, Jarosław Wilczyński, Ludovic Orlando, Magdalena Moskal-del-Hoyo, Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III Paul Sabatier, Centre National de la Recherche Scientifique (France), European Research Council, and Russian Foundation for Basic Research

Subjects
0106 biological sciences, Endogenous content, DNA damage, [SDV]Life Sciences [q-bio], 300 Social sciences, sociology & anthropology, 610 Medicine & health, Computational biology, Biology, 010603 evolutionary biology, 01 natural sciences, Genome, DNA hybridization-caputre techniques, Automation, 03 medical and health sciences, chemistry.chemical_compound, Genetics, Animals, Horses, Performance of hyRad, DNA, Ancient, ComputingMilieux_MISCELLANEOUS, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Ancient DNA, business.industry, RNA, RNA Probes, Sequence Analysis, DNA, Restriction enzyme, chemistry, [SDE]Environmental Sciences, business, DNA, Biotechnology
Abstract

DNA hybridization-capture techniques allow researchers to focus their sequencing efforts on preselected genomic regions. This feature is especially useful when analys- ing ancient DNA (aDNA) extracts, which are often dominated by exogenous environ- mental sources. Here, we assessed, for the first time, the performance of hyRAD as an inexpensive and design-free alternative to commercial capture protocols to obtain authentic aDNA data from osseous remains. HyRAD relies on double enzymatic re- striction of fresh DNA extracts to produce RNA probes that cover only a fraction ofthe genome and can serve as baits for capturing homologous fragments from aDNA li- braries. We found that this approach could retrieve sequence data from horse remains coming from a range of preservation environments, including beyond radiocarbon range, yielding up to 146.5-fold on-target enrichment for aDNA extracts showing ex- tremely low endogenous content (20%¿30%), while the fraction of endogenous reads mapping on- and off-target was relatively insensi- tive to the original endogenous DNA content. Procedures based on two instead of a single round of capture increased on-target coverage up to 3.6-fold. Additionally, we used methylation-sensitive restriction enzymes to produce probes targeting hypo- methylated regions, which improved data quality by reducing post-mortem DNA dam- age and mapping within multicopy regions. Finally, we developed a fully automated hyRAD protocol utilizing inexpensive robotic platforms to facilitate capture process- ing. Overall, our work establishes hyRAD as a cost-effective strategy to recover a set of shared orthologous variants across multiple ancient samples., This project received funding from: the University Paul Sabatier IDEX Chaire d’Excellence (OURASI); the CNRS Programme de Recherche Conjoint (PRC); the CNRS International Research Project (IRP AMADEUS); the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 797449; the Russian Foundation for Basic Research, project No. 19-59-15001 “Horses and their importance in the life of the ancient population of Altai and adjacent territories: interdisciplinary research and reconstruction”; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 681605).

Published
2022
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8. Sex in the city: Uncovering sex-specific management of equine resources from prehistoric times to the Modern Period in France

Author

Benoît Clavel, Sébastien Lepetz, Lorelei Chauvey, Stéphanie Schiavinato, Laure Tonasso-Calvière, Xuexue Liu, Antoine Fages, Naveed Khan, Andaine Seguin-Orlando, Clio Der Sarkissian, Pierre Clavel, Oscar Estrada, Duha Alioğlu, Charleen Gaunitz, Jean-Marc Aury, Maude Barme, Pierre Bodu, Monique Olive, Olivier Bignon-Lau, Jean-Christophe Castel, Myriam Boudadi-Maligne, Nicolas Boulbes, Alice Bourgois, Franck Decanter, Sylvain Foucras, Stéphane Frère, Armelle Gardeisen, Gaëtan Jouanin, Charlotte Méla, Nicolas Morand, Ariadna Nieto Espinet, Aude Perdereau, Olivier Putelat, Julie Rivière, Opale Robin, Marilyne Salin, Silvia Valenzuela-Lamas, Christian Vallet, Jean-Hervé Yvinec, Patrick Wincker, Ludovic Orlando, Ethnologie préhistorique, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Technologie et Ethnologie des Mondes Préhistoriques (TEMPS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), 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)-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)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Archéologique de la Vallée de l'Oise (CRAVO), Muséum national d'Histoire naturelle (MNHN), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Museum d'Histoire Naturelle [Genève] (MHN), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Archéologie et Archéométrie (ArAr), Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Direction Archéologie et Muséum de la ville d'Aix-en-Provence, Centre Technique Municipal RTE des Milles Aix-en-Provence, Institut Royal des Sciences Naturelles de Belgique (IRSNB), Archéologie et histoire ancienne : Méditerranée - Europe (ARCHIMEDE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Institución Milá y Fontanals de investigación en Humanidades (IMF), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-17-EURE-0010,CHESS,Toulouse Graduate School défis en économie et sciences sociales quantitatives(2017), European Project: 681605,PEGASUS, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Departamento de Arqueologı'a y Antropologı'a, Istitucio' Mila' i Fontanals, (IMF CSIC), Consejo Superior de Investigaciones Cientıficas (IMF-CSIC), Centre National de la Recherche Scientifique (France), European Research Council, France Génomique, Université de Toulouse, Villum Fonden, and Agence Nationale de la Recherche (France)

Subjects
Archeology, Ancient DNA, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Iron age, City, Breeding, Horse, Middle ages, Roman period, [SHS]Humanities and Social Sciences, Donkey, [SDE]Environmental Sciences, Husbandry, Hunting, Mule, Archaeozoology
Abstract

Sex identification from fragmentary archeozoological assemblages is particularly challenging in the Equid family, including for horses, donkeys and their hybrids. This limitation has precluded in-depth investigations of sex-ratio variation in various temporal, geographic and social contexts. Recently, shallow DNA sequencing has offered an economical solution to equine sex determination, even in environments where DNA preservation conditions is not optimal. In this study, we applied state-of-the-art methods in ancient DNA-based equine sex determination to 897 osseous remains in order to assess whether equal proportions of males and females could be found in a range of archeological contexts in France. We found Magdalenian horse hunt not focused on isolated bachelors, and Upper Paleolithic habitats and natural traps equally balancing sex ratios. In contrast, Iron Age sacrificial rituals appeared to have been preferentially oriented to male horses and this practice extended into the Roman Period. During Antiquity, the Middle Ages and the Modern Period, cities emerged as environments largely dominated by horse males. This strong sex-bias was considerably reduced, and sometimes even absent, in various rural contexts. Combined with previous archaeozoological work and textual evidence, our results portray an urban economy fueled by adult, often old, males, and rural environments where females and subadults of both sexes were maintained to sustain production demands., We thank Agnès Orsoni, Michela Leonardi, and Stefanie Wagner for lab assistance and all members of the AGES research team at CAGT for fruitful discussions. We also thank all archaeologists, curators and staff in charge of archaeological warehouses, who have facilitated access to the material analyzed in this study. Pierre Clavel’s PhD position is funded by the CNRS MITI interdisciplinary programme (‘Mission pour les Initiatives Transverses et Interdisciplinaires’). Xuexue Liu was supported by the European Union’s Horizon 2020 research and Innovation pro- gramme under the Marie Skłodowska-Curie grant agreement 101027750. This work was supported by the France G ́enomique Appel `a Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); the Initiative d’Excellence Chaires d’attractivit ́e, Universit ́e de Toulouse (OURASI) and the Villum Fonden miGENEPI research project. Andaine Seguin- Orlando acknowledges IAST for funding from ANR (France) under grant ANR-17-EURE-0010 (‘Investissements d’Avenir’ programme). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 681605).

Published
2022
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9. Historical management of equine resources in France from the Iron Age to the Modern Period

Author

Ludovic Orlando, Patrick Wincker, Julie Rivière, Nicolas Boulbes, Franck Decanter, Clio Der Sarkissian, Charleen Gaunitz, Naveed Khan, Jean-Marc Aury, Stéphane Frère, Silvia Valenzuela-Lamas, Maude Barme, Nicolas Morand, Sébastien Lepetz, Aude Perdereau, Charlotte Méla, Xuexue Liu, Duha Alioglu, Ariadna Nieto Espinet, Gaëtan Jouanin, Lorelei Chauvey, Laure Tonasso-Calvière, Christian Vallet, Jean-Hervé Yvinec, Olivier Putelat, Pierre Clavel, Marilyne Salin, Andaine Seguin-Orlando, Armelle Gardeisen, Oscar Estrada, Sylvain Foucras, Antoine Fages, Opale Robin, Benoît Clavel, Alice Bourgois, Stéphanie Schiavinato, European Research Council, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Université de Toulouse, Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Centre de Recherche Archéologique de la Vallée de l'Oise (CRAVO), Muséum national d'Histoire naturelle (MNHN), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Archéologie et Archéométrie (ArAr), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2), Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Direction Archéologie et Muséum de la ville d'Aix-en-Provence, Centre Technique Municipal RTE des Milles Aix-en-Provence, Archéologie et histoire ancienne : Méditerranée - Europe (ARCHIMEDE), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Department of Biotechnology, Abdul Wali Khan University (AWKU), Institute for Advanced Study in Toulouse (IAST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Archeodunum S.A. : investigations archéologiques, Institución Milá y Fontanals de investigación en Humanidades (IMF), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Archéologie d'Alsace, Service archéologique de Chartres, Service archéologique de la ville de Bourges, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ANR-17-EURE-0010,CHESS,Toulouse Graduate School défis en économie et sciences sociales quantitatives(2017), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), 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)-Université Paris-Saclay-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université de Perpignan Via Domitia (UPVD)

Subjects
0106 biological sciences, Archeology, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, [SDV]Life Sciences [q-bio], Distribution (economics), Breeding, Horse, 010603 evolutionary biology, 01 natural sciences, [SHS]Humanities and Social Sciences, 03 medical and health sciences, Late Antiquity, biology.animal, Donkey, Middle Ages, Hinny, ComputingMilieux_MISCELLANEOUS, Archaeozoology, 030304 developmental biology, 0303 health sciences, biology, Ancient DNA, business.industry, Roman Period, biology.organism_classification, Geography, Iron Age, Husbandry, Ethnology, Identification (biology), Equidae, business, Mule
Abstract

Alongside horses, donkeys and their first-generation hybrids represent members of the Equidae family known for their social, economic and symbolic importance in protohistoric and historical France. However, their relative importance and their respective roles in different regions and time periods are difficult to assess based on textual, iconographic and archaeological evidence. This is both due to incomplete, partial and scattered historical sources and difficulties to accurately assign fragmentary archaeological remains at the proper taxonomic level. DNA- based methods, however, allow for a robust identification of the taxonomic status of ancient equine osseous material from minimal sequence data. Here, we leveraged shallow ancient DNA sequencing and the dedicated Zonkey computational pipeline to obtain the first baseline distribution for horses, mules and donkeys in France from the Iron Age to the Modern period. Our collection includes a total of 873 ancient specimens spanning 128 sites and comprising 717 horses, 100 donkeys, 55 mules and a single hinny individual. While horses were ubiquitous and the most dominant species identified, our dataset reveals the importance of mule breeding during Roman times, especially between the 1st and 3rd centuries CE (Common Era), where they represented between 20.0% and 34.2% of equine assemblages. In contrast, donkeys were almost absent from northern France as- semblages during the whole Roman period, but replaced mules in rural and urban commercial and economic centers from the early Middle Ages. Our work also identified donkeys of exceptional size during Late Antiquity, which calls for a deep reassessment of the true morphological space of past equine species. This study confirmed the general preference toward horses throughout all time periods investigated but revealed dynamic manage- ment strategies leveraging the whole breadth of equine resources in various social, geographic and temporal contexts., Pierre Clavel’s PhD position is funded by the CNRS MITI interdisciplinary programme (Mission pour les Initiatives Transverses et Interdisciplinaires). Xuexue Liu was supported by the European Union’s Horizon 2020 research and Innovation programme under the Marie Skłodowska-Curie grant agreement 101027750. Andaine Seguin-Orlando acknowledges IAST for funding from ANR under grant ANR-17-EURE-0010 (Investissements d’Avenir programme). This work was supported by the France G ́enomique Appel `a Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); the Initiative d’Excellence Chaires d’attractivit ́e, Universit ́e de Toulouse (OURASI) and the Villum Fonden miGENEPI research project. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 681605)

Published
2021
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10. The origins and spread of domestic horses from the Western Eurasian steppes

Author

Enkhbayar Mijiddorj, G. G. Boeskorov, Vladimir V. Pitulko, Jamsranjav Bayarsaikhan, Jamiyan-Ombo Gantulga, Silvia Valenzuela Lamas, Sandrine Grouard, Morten E. Allentoft, Lubomír Peške, Henry Shephard, Marek Nowak, Viktória Kiss, Gottfried Brem, Kristian Kristiansen, Pam Crabtree, Krzysztof Tunia, Aude Perdereau, Jarosław Wilczyński, Svend Hansen, Diimaajav Erdenebaatar, Krisztina Somogyi, Tomasz Suchan, Rinat Zhumatayev, Valentin Dergachev, Elena Y. Pavlova, Aleksei Kasparov, Arturo Morales-Muñiz, Hossein Davoudi, Anna Szécsényi-Nagy, Valentin Dumitrașcu, Timo Seregély, Alan K. Outram, Natalia Berezina, Nikolay A. Bokovenko, Christoph Schwall, Tatiana Kuznetsova, Mariya A. Kusliy, Sergey K. Vasiliev, Michael Hofreiter, Bazartseren Boldgiv, Andrey Logvin, Robin Bendrey, Adrian Bălășescu, M. Marzullo, Kirill Yu. Kiryushin, Beth Shapiro, Laure Tonasso-Calvière, Mikhail A. Anisimov, John Southon, Saule Kalieva, Noémie Tomadini, Nadiia Kotova, Mietje Germonpré, Joris Peters, Benoît Clavel, Ahmed H. Alfarhan, Antoine Fages, Lembi Lōugas, Sandra Olsen, Eve Rannamäe, Daniel Gerber, Konstantin V. Chugunov, Naveed Khan, Benjamin S. Arbuckle, Keiko Kitagawa, Anna Lasota-Kuś, William B. Taylor, Alexander S. Graphodatsky, Sébastien Lepetz, Cheryl A. Makarewicz, Tumur-Ochir Iderkhangai, Alexej Kalmykov, Sebastián Celestino, Ilya Merz, Norbert Benecke, Juan Luis Arsuaga, Carmen Olària, Mikhail V. Sablin, David W. Anthony, Silvia Albizuri Canadell, Victor Varfolomeyev, Zsolt Gallina, Natalia S. Berezina, Jaime Lira Garrido, David Lordkipanize, Alekandr A. Vybornov, Gabriella Kulcsár, Nadir Alvarez, Umberto Tecchiati, Myriam Boudadi-Maligne, Andrey Epimakhov, Valeriy Loman, Olivier Bignon-Lau, Sylwia Pospuła, Patrick Wincker, Marjan Mashkour, Turbat Tsagaan, Duha Alioglu, Andaine Seguin-Orlando, Jean-Marc Aury, Clio Der Sarkissian, Giovanna Bagnasco Gianni, Ornella Prato, Pierre Bodu, Jean-Christophe Castel, Ekaterina Petrova, Charleen Gaunitz, Pavel A. Kosintsev, Philipp W. Stockhammer, Alexey A. Kovalev, Sabine Reinhold, Gennady F. Baryshnikov, Victor Logvin, Abdesh Toleubaev, Wolfgang Haak, Johannes Krause, Magdalena Moskal-del Hoyo, Rune Iversen, Esther Rodríguez González, Stéphanie Schiavinato, I. V. Kukushkin, Pablo Librado, Alexander Bessudnov, Alexander J.E. Pryor, Ma Pilar Iborra, Jérome Magail, Monique Olive, Roxana Dobrescu, Mélanie Pruvost, Barbara Wallner, Alexander N. Bessudnov, Sergazy Sakenov, Viktor Zaibert, N. L. Morgunova, Lutz Klassen, Alexander E. Basilyan, Balázs Gusztáv Mende, N Seregin, Aleksandr I. Yudin, Erika Gál, Natalya A. Plasteeva, Arne Ludwig, Saleh A. Alquraishi, Guus Kroonen, Ariadna Nieto Espinet, Aurore Fromentier, René Kyselý, Ludovic Orlando, Elina Ananyevskaya, A. Belinskiy, Victor Merz, Ghenadie Sîrbu, Irina Shevnina, Pavel Kuznetsov, Urmas Saarma, Kubatbeek Tabaldiev, Khaled A. S. Al-Rasheid, Marcel Keller, Alexey A. Tishkin, Pavel A. Nikolskiy, Emma Usmanova, Natalia Roslyakova, Lorelei Chauvey, Ethnologie préhistorique, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université Paris Nanterre (UPN)-Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université Paris Nanterre (UPN)-Université Paris 1 Panthéon-Sorbonne (UP1), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université Paris Nanterre (UPN)-Université Paris 1 Panthéon-Sorbonne (UP1), Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Settore L-ANT/01 - Preistoria e Protostoria, Cavalls--Ensinistrament, GRASSLAND, GENETICS, POPULATION, Steppe, 300 Social sciences, sociology & anthropology, Population genetics, HORSES, CENTRAL ASIA, [SHS]Humanities and Social Sciences, horse geneomes, Domestication, 0302 clinical medicine, EQUIDAE, ADAPTATION, 610 Medicine & health, Phylogeny, 0303 health sciences, education.field_of_study, Evolutionary genetics, geography.geographical_feature_category, equestrianism, Indo-Iranian languages, horse domestication, LOCOMOTION, Sintashta culture, Western Eurasian steppes, DOMESTIC HORSE, GENOME, Geography, Archaeology, DNA, ANCIENT, Cavalls--Història, [SDE]Environmental Sciences, Ethnology, Bronze Age, EUROPE, 780 Music, Article, Ancient, 03 medical and health sciences, Genetics, NONHUMAN, Horses, education, [SDV.GEN]Life Sciences [q-bio]/Genetics, Human evolutionary genetics, IBERIAN PENINSULA, ANIMALS, ANIMAL, DNA, Genetics, Population, DOMESTICATION, steppe pastoralists, 2nd millennium BC, 030217 neurology & neurosurgery, Settore BIO/05 - Zoologia, LANGUAGE, RUSSIAN FEDERATION, chariots, Faculty of Science, Neolithic, HORSE, Migration, Mobility, Multidisciplinary, Genome, ASIA, HORSEBACK RIDING, Grassland, Europe, STEPPE, Animals, Asia, DNA, Ancient, aDNA, spoke-wheeled chariots, GENETICS, PHYLOGENY, Population, Pastoralism, ARCHEOLOGY, Homeland, Indo-European, PASTORALISM, Yamnaya culture, Euràsia, ANCIENT DNA, VOLGA REGION, ARTICLE, 030304 developmental biology, 3rd millennium BC, Horseback riding, population genetics, ANATOLIA, EQUUS CABALLUS, TURKEY, ANIMAL WELFARE, Faculty of Humanities, ARCHAEOLOGICAL EVIDENCE
Abstract

Domestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 bc3. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture., The work by G. Boeskorov is done on state assignment of DPMGI SB RAS. This project was supported by the University Paul Sabatier IDEX Chaire d’Excellence (OURASI); Villum Funden miGENEPI research programme; the CNRS ‘Programme de Recherche Conjoint’ (PRC); the CNRS International Research Project (IRP AMADEUS); the France Génomique Appel à Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); IB10131 and IB18060, both funded by Junta de Extremadura (Spain) and European Regional Development Fund; Czech Academy of Sciences (RVO:67985912); the Zoological Institute ZIN RAS (АААА-А19-119032590102-7); and King Saud University Researchers Supporting Project (NSRSP–2020/2). The research was carried out with the financial support of the Russian Foundation for Basic Research (19-59-15001 and 20-04-00213), the Russian Science Foundation (16-18-10265, 20-78-10151, and 21-18-00457), the Government of the Russian Federation (FENU-2020-0021), the Estonian Research Council (PRG29), the Estonian Ministry of Education and Research (PRG1209), the Hungarian Scientific Research Fund (Project NF 104792), the Hungarian Academy of Sciences (Momentum Mobility Research Project of the Institute of Archaeology, Research Centre for the Humanities); and the Polish National Science Centre (2013/11/B/HS3/03822). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (grant agreement 797449). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements 681605, 716732 and 834616).

Published
2021
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11. CASCADE: A Custom-Made Archiving System for the Conservation of Ancient DNA Experimental Data

Author

Andaine Seguin-Orlando, Clio Der Sarkissian, Antoine Fages, Stefanie Wagner, Aurore Fromentier, Dirk Dolle, Xavier Mata, Stéphanie Schiavinato, Lorelei Chauvey, Laure Tonasso-Calvière, Ludovic Orlando, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and University of Copenhagen = Københavns Universitet (KU)

Subjects
0106 biological sciences, 0301 basic medicine, Traceability, Computer science, Test data generation, Sample (material), lcsh:Evolution, Genomics, collaborative sharing, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, lcsh:QH540-549.5, lcsh:QH359-425, LIMS, ancient DNA, Ecology, Evolution, Behavior and Systematics, database, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Ecology, business.industry, Information sharing, conservation, Automation, Data science, laboratory management, Management information systems, 030104 developmental biology, Ancient DNA, traceability, lcsh:Ecology, business
Abstract

International audience; The field of ancient genomics has undergone a true revolution during the last decade. Input material, time requirements and processing costs have first limited the number of specimens amenable to genome sequencing. However, the discovery that archeological material such as petrosal bones can show increased ancient DNA preservation rates, combined with advances in sequencing technologies, molecular methods for the recovery of degraded DNA fragments and bioinformatics, has vastly expanded the range of samples compatible with genome-wide investigation. Experimental procedures for DNA extraction, genomic library preparation and target enrichment have become more streamlined, and now also include automation. These procedures have considerably reduced the amount of work necessary for data generation, effectively adapting the processing capacity of individual laboratories to the increasing numbers of analyzable samples. Handling vast amounts of samples, however, comes with logistical challenges. Laboratory capacities, equipment, and people need to be efficiently coordinated, and the progress of each sample through the different experimental stages needs to be fully traceable, especially as archeological remains of animals or plants are often provided and/or handled by many different collaborators. Here we present CASCADE, a laboratory information management system (LIMS) dealing with the specificities of ancient DNA sample processing and tracking, applicable by large and small laboratories alike, and scalable to large projects involving the analysis of thousands of samples and more. By giving an account of the specimen's progress at any given analytical step, CASCADE not only optimizes the collaborative experience, including real-time information sharing with third parties, but also improves the efficacy of data generation and traceability in-house.

Published
2020
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12. Targeted Exon Skipping Restores Type VII Collagen Expression and Anchoring Fibril Formation in an In Vivo RDEB Model

Author

Sandrina Turczynski, Audrey Décha, Matthias Titeux, Akemi Ishida-Yamamoto, Laure Tonasso, and Alain Hovnanian

Subjects
Keratinocytes, 0301 basic medicine, Collagen Type VII, RNA Splicing, Blotting, Western, Mice, Nude, Dermatology, Real-Time Polymerase Chain Reaction, Transfection, Biochemistry, Mice, Random Allocation, 03 medical and health sciences, Exon, 0302 clinical medicine, Anchoring fibrils, medicine, Animals, Humans, Skin equivalent, Genetic Predisposition to Disease, Molecular Biology, Cells, Cultured, integumentary system, Chemistry, Epidermolysis bullosa dystrophica, Exons, Cell Biology, medicine.disease, Molecular biology, Complement C7, Exon skipping, Epidermolysis Bullosa Dystrophica, Disease Models, Animal, Open reading frame, 030104 developmental biology, Gene Expression Regulation, 030220 oncology & carcinogenesis, RNA splicing, Collagen
Abstract

Dystrophic epidermolysis bullosa is a group of orphan genetic skin diseases dominantly or recessively inherited, caused by mutations in COL7A1 encoding type VII collagen, which forms anchoring fibrils. Individuals with recessive dystrophic epidermolysis bullosa develop severe skin and mucosal blistering after mild trauma. The exon skipping strategy consists of modulating splicing of a pre-mRNA to induce skipping of a mutated exon. We have targeted COL7A1 exons 73 and 80, which carry recurrent mutations and whose excision preserves the open reading frame. We first showed the dispensability of these exons for type VII collagen function in vivo. We then showed that transfection of primary recessive dystrophic epidermolysis bullosa keratinocytes and fibroblasts carrying null mutations in exon 73 and/or 80, with 2′- O -methyl antisense oligoribonucleotides, led to efficient ex vivo skipping of these exons (50–95%) and resulted in a significant level (up to 36%) of type VII collagen re-expression. Finally, one or two subcutaneous injections of antisense oligoribonucleotides at doses ranging from 400 μg up to 1 mg restored type VII collagen expression and anchoring fibril formation in vivo in a xenograft model of recessive dystrophic epidermolysis bullosa skin equivalent. This work provides a proof of principle for the treatment of patients with recessive dystrophic epidermolysis bullosa by exon skipping using subcutaneous administration of antisense oligoribonucleotides.

Published
2016
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13. Oral health status in historic population: Macroscopic and metagenomic evidence

Author

Pierre Chevet, Claire Willmann, Xavier Mata, Catherine Thèves, Elodie Cabot, Lenka Tisseyre, Céline Jeziorski, Ludovic Orlando, Rémi Esclassan, Kristian Hanghoej, Laure Tonasso, Eric Crubézy, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Section for GeoGenetics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Department of Animal Biology and Genetics, University of Florence (UNIFI), ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR: 10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2011), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)

Subjects
Male, Rural Population, 0301 basic medicine, Teeth, Physiology, Health Status, Digestive Physiology, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Rothia dentocariosa, lcsh:Medicine, Oral Health, History, 18th Century, Pathology and Laboratory Medicine, Diagnostic Radiology, Streptococcus mutans, 0302 clinical medicine, Oral Diseases, Medicine and Health Sciences, Tannerella forsythia, lcsh:Science, rothia-dentocariosa, ancient dna, dental-caries, streptococcus-mutan, pseudoramibacter-alactolyticus, tannerella-forsythia, periodontal-disease, treponema-denticola, parvimonas-micra, teeth, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Multidisciplinary, Calculus, biology, Shotgun sequencing, Microbiota, Radiology and Imaging, Periodontal diseases, Genomics, Bone Imaging, Medical Microbiology, X-ray radiography, Physical Sciences, Female, France, Genomic libraries, Anatomy, Pathogens, Research Article, Autre (Sciences du Vivant), DNA, Bacterial, Imaging Techniques, Oral Medicine, Population, Dental Caries, Research and Analysis Methods, Microbiology, DNA sequencing, 03 medical and health sciences, Diagnostic Medicine, Genetics, Humans, Dentition, DNA, Ancient, Periodontitis, education, Parvimonas micra, Microbial Pathogens, Paleodontology, Bacteria, lcsh:R, Organisms, Biology and Life Sciences, Streptococcus, Computational Biology, 030206 dentistry, Genome Analysis, biology.organism_classification, stomatognathic diseases, 030104 developmental biology, Ancient DNA, Jaw, Metagenomics, lcsh:Q, Bacterial pathogens, Digestive System, Head, Mathematics
Abstract

International audience; Recent developments in High-Throughput DNA sequencing (HTS) technologies and ancient DNA (aDNA) research have opened access to the characterization of the microbial communities within past populations. Most studies have, however, relied on the analysis of dental calculus as one particular material type particularly prone to the molecular preservation of ancient microbial biofilms and potential of entire teeth for microbial characterization, both of healthy communities and pathogens in ancient individuals, remains overlooked. In this study, we used shotgun sequencing to characterize the bacterial composition from historical subjects showing macroscopic evidence of oral pathologies. We first carried out a macro-scopic analysis aimed at identifying carious or periodontal diseases in subjects belonging to a French rural population of the 18th century AD. We next examined radiographically six subjects showing specific, characteristic dental pathologies and applied HTS shotgun sequencing to characterize the microbial communities present in and on the dental material. The presence of Streptococcus mutans and also Rothia dentocariosa, Actinomyces visco-sus, Porphyromonas gingivalis, Tannerella forsythia, Pseudoramibacter alactolyticus, Olse-nella uli and Parvimonas micra was confirmed through the presence of typical signatures of post-mortem DNA damage at an average depth-of-coverage ranging from 0.5 to 7X, with a minimum of 35% (from 35 to 93%) of the positions in the genome covered at least once. Each sampled tooth showed a specific bacterial signature associated with carious or peri-odontal pathologies. This work demonstrates that from a healthy independent tooth, without visible macroscopic pathology, we can identify a signature of specific pathogens and deduce the oral health status of an individual.

Published
2018
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14. Poster Abstracts

Author

Patricia Tortevoye, Antoine Gessain, Laure Tonasso, Evelyne Guitard, Sabine Plancoulaine, Nicolas Brucato, Jean-Michel Dugoujon, Olivier Cassar, Florence Migot-Nabias, and Georges Larrouy

Subjects
Genetics, Mitochondrial DNA, Genetic diversity, Infectious Diseases, biology, Virology, Immunology, Marron, Settlement (litigation), biology.organism_classification, Y chromosome, Genotyping
Published
2009
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15. A frequent functional SNP in theMMP1promoter is associated with higher disease severity in recessive dystrophic epidermolysis bullosa

Author

Audrey Décha, Alain Hovnanian, Laure Tonasso, Valérie Pendaries, Matthias Titeux, and Christine Bodemer

Subjects
Adult, Collagen Type VII, Adolescent, MMP1, Genes, Recessive, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Gene Expression Regulation, Enzymologic, White People, Cohort Studies, Polymorphism (computer science), Genotype, Genetics, medicine, Humans, SNP, Genetic Predisposition to Disease, RNA, Messenger, Promoter Regions, Genetic, Gene, Cells, Cultured, Genetics (clinical), Genetic association, Mutation, Binding Sites, Proto-Oncogene Proteins c-ets, Fibroblasts, Phenotype, Epidermolysis Bullosa Dystrophica, France, Matrix Metalloproteinase 1
Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the COL7A1 gene encoding type VII collagen. Variations in severity between the different clinical forms of RDEB likely depend on the nature and location of COL7A1 mutations, but observed intrafamilial phenotypic variations suggest additional genetic and/or environmental factors. Candidate modifier genes include MMP1, encoding matrix metalloproteinase 1, the first gene implicated in RDEB before its primary role in the disease was excluded. Type VII collagen is a substrate of MMP1 and an imbalance between its synthesis and degradation could conceivably worsen the RDEB phenotype. Here, we studied a previously described family with three affected siblings of identical COL7A1 genotype but displaying great sibling-to-sibling variations in disease severity. RDEB severity did not correlate with type VII collagen synthesis levels, but with protein levels at the dermal-epidermal junction, suggesting increased degradation by metalloproteinases. This was supported by the presence of increased transcript and active MMP1 levels in the most severely affected children, who carried a known SNP (1G/2G) in the MMP1 promoter. This SNP creates a functional Ets binding site resulting in transcriptional upregulation. We next studied a French cohort of 31 unrelated RDEB patients harboring at least one in-frame COL7A1 mutation, ranging from mild localized RDEB to the severe Hallopeau-Siemens form. We found a strong genetic association between the 2G variant and the Hallopeau-Siemens disease type (odds ratio: 73.6). This is the first example of a modifier gene in RDEB and has implications for its prognosis and possible new treatments.

Published
2008
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16. Determined about sex: Sex-testing in 45 primate species using a 2Y/1X sex-typing assay

Author

Caroline Bouakaze, Myriam Croze, José Braga, Patricia Balaresque, Laure Tonasso, Jean-Luc Fausser, Valérie Choesmel Cadamuro, Stéphanie Schiavinato, Jean-Michel Dugoujon, Patrice Gerard, Morgane Gibert, Laboratoire d'Anthropologie Moléculaire, Institut de Médecine Légale, Strasbourg, France (IML), Université Louis Pasteur - Strasbourg I, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Instituto Nacional de Pesquisas Espaciais (INPE), Ministério da Ciência, Tecnologia e Inovação, Department of Genetics [Leicester], University of Leicester, ANR-11-LABX-0010/11-LABX-0010,LabEx DRIIHM,Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux(2011), ANR-11-LABX-0010,DRIIHM / IRDHEI,Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux(2011), Faculty of Biology, LMU Munich, Planegg-Martinsried, Germany, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Molecular Genetic Technique, Male, Primates, X Chromosome, Molecular Sequence Data, Population genetics, Locus (genetics), Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Sequence Homology, Nucleic Acid, Y Chromosome, Multiplex polymerase chain reaction, Genetics, Animals, Humans, 030216 legal & forensic medicine, Typing, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Base Sequence, DNA, Sex Determination Processes, biology.organism_classification, [SDE.ES]Environmental Sciences/Environmental and Society, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Indriidae, Testis determining factor, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Anthropoidea, Female, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Multiplex Polymerase Chain Reaction
Abstract

Sex-testing using molecular genetic technique is routinely used in the fields of forensics, population genetics and conservation biology. However, none of the assay used so far allows a non-ambiguous and successful sex determination for human and non-human primate species. The most widely used method, AMELY/X, and its alternatives suffer from a set of drawbacks in humans and can rarely be used in New World primate species. Here, we designed a new sex-typing assay using a multiplexed PCR amplification of UTX and UTY-homologous loci and combined male-specific SRY locus. This method was successfully tested on 1048 samples, including 82 non-human primates from 45 Anthropoidea and Lemuriformes species and 966 human samples from 24 populations (Africans, Europeans, and South Americans). This sex-typing method is applicable across all primate species tested from Hominoidea to Indriidae, and also on various populations with different background origins; it represents a robust and cheap sex-typing assay to be used both by the anthropologist and primatologist communities.

Published
2015
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17. Tracing Arab-Islamic inheritance in Madagascar: study of the Y-chromosome and mitochondrial DNA in the Antemoro

Author

Harilanto Razafindrazaka, Laure Tonasso, Mamisoa Adelta Ratolojanahary, Louis-Paul Randriamarolaza, Mélanie Capredon, Nicolas Brucato, Jean-Michel Dugoujon, Bernard Champion, François-Xavier Ricaut, Valérie Choesmel-Cadamuro, Andriamihaja Bakomalala Rakotondrabe, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherches Littéraires et Historiques de l'Océan Indien (CRLHOI), Contacts de Cultures, de Littératures et de Civilisations (CCLC), Université de La Réunion (UR)-Université de La Réunion (UR), Human Genetics, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Université d'Antananarivo, Déplacements, Identités, Regards, Écritures (DIRE), Université de La Réunion (UR), Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
Male, Asia, Population genetics, Genetic genealogy, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Inheritance Patterns, Ethnic group, lcsh:Medicine, Human genetic variation, Biology, Southeast asian, DNA, Mitochondrial, Islam, Haplogroup, Comoros, 03 medical and health sciences, Databases, Genetic, Ethnicity, Madagascar, Humans, lcsh:Science, 030304 developmental biology, Recombination, Genetic, Genetics, Principal Component Analysis, 0303 health sciences, Chromosomes, Human, Y, Multidisciplinary, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Geography, lcsh:R, 030305 genetics & heredity, Haplotype, Arabs, Phylogeography, Haplotypes, Evolutionary biology, Africa, Haplogroups, Female, lcsh:Q, Gene pool, Microsatellite Repeats, Research Article
Abstract

International audience; Madagascar is located at the crossroads of the Asian and African worlds and is therefore of particular interest for studies on human population migration. Within the large human diversity of the Great Island, we focused our study on a particular ethnic group, the Antemoro. Their culture presents an important Arab-Islamic influence, but the question of an Arab biological inheritance remains unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this ethnic group. Although the majority of Antemoro genetic ancestry comes from sub-Saharan African and Southeast Asian gene pools, we observed in their paternal lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins. This inheritance was restricted to some Antemoro sub-groups. Statistical analyses tended to confirm significant Middle Eastern genetic contribution. This study gives a new perspective to the large human genetic diversity in Madagascar.

Published
2013
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18. siRNA-mediated allele-specific inhibition of mutant type VII collagen in dominant dystrophic epidermolysis bullosa

Author

Laure Tonasso, Alain Hovnanian, Matthias Titeux, Géraldine Gasc, Valérie Pendaries, and José E. Mejía

Subjects
Collagen Type VII, Mutant, RNA, Cell Biology, Dermatology, Genetic Therapy, Biology, Molecular biology, Biochemistry, Epidermolysis Bullosa Dystrophica, Type VII collagen, Humans, RNA, Small Interfering, Gene, Dominant dystrophic epidermolysis bullosa, Molecular Biology, Allele specific, Genes, Dominant
Published
2012

19. The imprint of the Slave Trade in an African American population: mitochondrial DNA, Y chromosome and HTLV-1 analysis in the Noir Marron of French Guiana

Author

Georges Larrouy, Olivier Cassar, Antoine Gessain, Evelyne Guitard, Jean-Michel Dugoujon, Patricia Tortevoye, Laure Tonasso, Florence Migot-Nabias, Sabine Plancoulaine, Nicolas Brucato, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Anthropologie Moléculaire et Imagerie de Synthèse ( AMIS ), PRES Université de Toulouse-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut de Recherche pour le Développement ( IRD ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Gau, Mireille

Subjects
Male, Social Problems, Evolution, Range (biology), Genetic genealogy, Biology, Marron, DNA, Mitochondrial, Maroon, 03 medical and health sciences, Genetic drift, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, parasitic diseases, QH359-425, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Phylogeny, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Human T-lymphotropic virus 1, 0303 health sciences, Genetic diversity, Chromosomes, Human, Y, 030305 genetics & heredity, biology.organism_classification, French Guiana, Black or African American, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Evolutionary biology, Ethnology, Female, Gene pool, Research Article, Founder effect
Abstract

Background Retracing the genetic histories of the descendant populations of the Slave Trade (16th-19th centuries) is particularly challenging due to the diversity of African ethnic groups involved and the different hybridisation processes with Europeans and Amerindians, which have blurred their original genetic inheritances. The Noir Marron in French Guiana are the direct descendants of maroons who escaped from Dutch plantations in the current day Surinam. They represent an original ethnic group with a highly blended culture. Uniparental markers (mtDNA and NRY) coupled with HTLV-1 sequences (env and LTR) were studied to establish the genetic relationships linking them to African American and African populations. Results All genetic systems presented a high conservation of the African gene pool (African ancestry: mtDNA = 99.3%; NRY = 97.6%; HTLV-1 env = 20/23; HTLV-1 LTR = 6/8). Neither founder effect nor genetic drift was detected and the genetic diversity is within a range commonly observed in Africa. Higher genetic similarities were observed with the populations inhabiting the Bight of Benin (from Ivory Coast to Benin). Other ancestries were identified but they presented an interesting sex-bias. Whilst male origins spread throughout the north of the bight (from Benin to Senegal), female origins were spread throughout the south (from the Ivory Coast to Angola). Conclusions The Noir Marron are unique in having conserved their African genetic ancestry, despite major cultural exchanges with Amerindians and Europeans through inhabiting the same region for four centuries. Their maroon identity and the important number of slaves deported in this region have maintained the original African diversity. All these characteristics permit to identify a major origin located in the former region of the Gold Coast and the Bight of Benin; regions highly impacted by slavery, from which goes a sex-biased longitudinal gradient of ancestry.

Published
2010
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20. mtDNA and Y-chromosome diversity in Aymaras and Quechuas from Bolivia: different stories and special genetic traits of the Andean Altiplano populations

Author

René Vasquez, Pedro Moral, Magdalena Gayà-Vidal, Laure Tonasso, Nancy Saenz-Ruales, Mercedes Villena, Jean-Michel Dugoujon, Pascale Gerbault, and Claudio M. Bravi

Subjects
Genetic Markers, Male, Mitochondrial DNA, Bolivia, media_common.quotation_subject, Population, Population genetics, HUMAN POPULATIONS, Biology, Y chromosome, DNA, Mitochondrial, Polymorphism, Single Nucleotide, Haplogroup, Ciencias Biológicas, Genética y Herencia, Humans, education, media_common, Language, UNIPARENTAL MARKERS, education.field_of_study, Analysis of Variance, Chromosomes, Human, Y, Indians, South American, Haplotype, NATIVE AMERICANS, Genetics, Population, Haplotypes, Genetic marker, Evolutionary biology, Anthropology, Female, Anatomy, ANDEAN REGION, CIENCIAS NATURALES Y EXACTAS, Diversity (politics), Demography, Microsatellite Repeats
Abstract

Two Bolivian samples belonging to the two main Andean linguistic groups (Aymaras and Quechuas) were studied for mtDNA and Y-chromosome uniparental markers to evaluate sex-specific differences and give new insights into the demographic processes of the Andean region. mtDNA-coding polymorphisms, HVI-HVII control regions, 17 Y-STRs, and three SNPs were typed in two well-defined populations with adequate size samples. The two Bolivian samples showed more genetic differences for the mtDNA than for the Y-chromosome. For the mtDNA, 81% of Aymaras and 61% of Quechuas presented haplogroup B2. Native American Y-chromosomes were found in 97% of Aymaras (89% hg Q1a3a and 11% hg Q1a3*) and 78% of Quechuas (100% hg Q1a3a). Our data revealed high diversity values in the two populations, in agreement with other Andean studies. The comparisons with the available literature for both sets of markers indicated that the central Andean area is relatively homogeneous. For mtDNA, the Aymaras seemed to have been more isolated throughout time, maintaining their genetic characteristics, while the Quechuas have been more permeable to the incorporation of female foreigners and Peruvian influences. On the other hand, male mobility would have been widespread across the Andean region according to the homogeneity found in the area. Particular genetic characteristics presented by both samples support a past common origin of the Altiplano populations in the ancient Aymara territory, with independent, although related histories, with Peruvian (Quechuas) populations. Fil: Gayà Vidal, Magdalena. Universidad de Barcelona; España Fil: Moral, Pedro. Universidad de Barcelona; España Fil: Saenz Ruales, Nancy. Université Paul Sabatier; Francia Fil: Gerbault, Pascale. Universite de Toulouse Iii Paul Sabatier; Francia Fil: Tonasso, Laure. Université Paul Sabatier; Francia Fil: Villena, Mercedes. Universidad Mayor de San Andres; Bolivia Fil: Vasquez, René. Universidad Autonoma Tomas Frias; Bolivia Fil: Bravi, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Dugoujon, Jean Michel. Université Paul Sabatier; Francia

Published
2010

21. SIN Retroviral Vectors Expressing COL7A1 Under Human Promoters for Ex Vivo Gene Therapy of Recessive Dystrophic Epidermolysis Bullosa

Author

Olivier Danos, Maria Antonietta Zanta-Boussif, Alain Hovnanian, Valérie Pendaries, Agnes Brice, José E. Mejía, Laure Tonasso, Matthias Titeux, N. Pironon, and Audrey Décha

Subjects
Keratinocytes, Collagen Type VII, Blotting, Western, Genetic Vectors, Human skin, Mice, SCID, Biology, Polymerase Chain Reaction, Viral vector, law.invention, Mice, Microscopy, Electron, Transmission, In vivo, law, Drug Discovery, Anchoring fibrils, Genetics, medicine, Animals, Humans, Promoter Regions, Genetic, Molecular Biology, Cells, Cultured, Pharmacology, integumentary system, Epidermolysis bullosa dystrophica, Fibroblasts, medicine.disease, Molecular biology, Immunohistochemistry, Epidermolysis Bullosa Dystrophica, Blotting, Southern, Retroviridae, Recombinant DNA, Molecular Medicine, Original Article, Stem cell, Ex vivo
Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by loss-of-function mutations in COL7A1 encoding type VII collagen which forms key structures (anchoring fibrils) for dermal-epidermal adherence. Patients suffer since birth from skin blistering, and develop severe local and systemic complications resulting in poor prognosis. We lack a specific treatment for RDEB, but ex vivo gene transfer to epidermal stem cells shows a therapeutic potential. To minimize the risk of oncogenic events, we have developed new minimal self-inactivating (SIN) retroviral vectors in which the COL7A1 complementary DNA (cDNA) is under the control of the human elongation factor 1alpha (EF1alpha) or COL7A1 promoters. We show efficient ex vivo genetic correction of primary RDEB keratinocytes and fibroblasts without antibiotic selection, and use either of these genetically corrected cells to generate human skin equivalents (SEs) which were grafted onto immunodeficient mice. We achieved long-term expression of recombinant type VII collagen with restored dermal-epidermal adherence and anchoring fibril formation, demonstrating in vivo functional correction. In few cases, rearranged proviruses were detected, which were probably generated during the retrotranscription process. Despite this observation which should be taken under consideration for clinical application, this preclinical study paves the way for a therapy based on grafting the most severely affected skin areas of patients with fully autologous SEs genetically corrected using a SIN COL7A1 retroviral vector.

Published
2010

22. Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

Author

Murray P. Cox, Harilanto Razafindrazaka, François-X Ricaut, Louis P Randriamarolaza, Laure Tonasso, Jean-Michel Dugoujon, Eric Crubézy, Bertrand Ludes, Evelyne Guitard, Maru Mormina, Aix Marseille Université (AMU), Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS), Leverhulme Centre for Human Evolutionary Studies University of Cambridge, University of Cambridge [UK] (CAM), Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Médecine Légale - IML (Paris, France), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Mitochondrial DNA, Molecular Sequence Data, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Biology, DNA, Mitochondrial, DNA sequencing, Haplogroup, Polynesia, Article, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, Genetics, Humans, Genetics (clinical), Phylogeny, 030304 developmental biology, 0303 health sciences, Polymorphism, Genetic, Phylogenetic tree, Base Sequence, 030305 genetics & heredity, Haplotype, Genetic Variation, Genetics, Population, Haplotypes, Motif (music), Human mitochondrial DNA haplogroup
Abstract

International audience; More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself.

Published
2010
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23. Genetic Admixture and Flavor Preferences: Androstenone Sensitivity in Malagasy Populations

Author

Dina Razafindrazaka, Harilanto Razafindrazaka, Thierry Letellier, Laure Tonasso, Denis Pierron, Jean-Aimé Rakotoarisoa, Chantal Radimilahy, Stéphanie Schiavinato, and Aurore Monnereau

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Swine, Population, Genetic admixture, Biology, Olfaction Disorders, Young Adult, chemistry.chemical_compound, Polymorphism (computer science), Internal medicine, Madagascar, Genetics, medicine, Animals, Humans, education, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, education.field_of_study, Polymorphism, Genetic, Significant difference, Androstenone, Middle Aged, Flavor preferences, Choice test, Smell, Endocrinology, chemistry, Sex pheromone, Odorants, Taste Threshold, Androstanes
Abstract

The genetic basis of androstenone anosmia has been well studied due to androstenone's putative role as a human sex pheromone and its presence in pork meat. Polymorphisms have been identified on the olfactory receptor gene OR7D4, which significantly affect perception of androstenone pleasantness and intensity in several Western populations. This study aims to investigate androstenone sensitivity and the influence of OR7D4 polymorphisms in non-Western populations. Androstenone perception was tested in 132 individuals from Madagascar using a double three-alternative choice test with two concentrations of androstenone (0.17 and 1.7 µg/ml). We found that Malagasy populations described this molecule in a similar way to European populations, and 21% of the sample was not able to smell androstenone. In contrast to previous studies, there was no significant evidence of the influence of rs61729907: C>T (R88W) and rs5020278: C>T polymorphisms (T133M) on androstenone sensitivity in Malagasy populations. We found, however, a significant effect of the polymorphism rs61732668 (P79L) and a significant difference in androstenone perception between populations in different locations across Madagascar. This study indicates the existence of population-specific factors in androstenone sensitivity, suggesting that population history has a role in shaping an individual's smell and flavor preferences and food preferences in general.

Published
2015
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24. Human Keratinocytes Acquire Cellular Cytotoxicity under UV-B Irradiation

Author

Christine Jean, Caroline Baudouin, Guy Laurent, Marie-José Haure, Matthias Titeux, Anne Quillet-Mary, Alexandra Charruyer, Hélène Hernandez-Pigeon, Marie Charveron, Laure Tonasso, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), CHU Toulouse [Toulouse]-Institut Claudius Regaud-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoires Expanscience, Laboratoires Expanscience, R&D, Laboratoire de Biologie Cellulaire Cutanée, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, and Institut de Recherche Pierre Fabre

Subjects
Photoaging, Human skin, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Cytotoxic T cell, Epidermal growth factor receptor, Cytotoxicity, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, integumentary system, biology, Cell Biology, medicine.disease, 3. Good health, Cell biology, Granzyme B, medicine.anatomical_structure, Perforin, 030220 oncology & carcinogenesis, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Keratinocyte, hormones, hormone substitutes, and hormone antagonists
Abstract

Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin.

Published
2006
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25. Human keratinocytes acquire cellular cytotoxicity under UV-B irradiation. Implication of granzyme B and perforin

Author

Hélène, Hernandez-Pigeon, Christine, Jean, Alexandra, Charruyer, Marie-José, Haure, Matthias, Titeux, Laure, Tonasso, Anne, Quillet-Mary, Caroline, Baudouin, Marie, Charveron, and Guy, Laurent

Subjects
Keratinocytes, Pore Forming Cytotoxic Proteins, Membrane Glycoproteins, MAP Kinase Signaling System, Perforin, Ultraviolet Rays, T-Lymphocytes, Serine Endopeptidases, Granzymes, Cell Line, ErbB Receptors, Gene Expression Regulation, Humans, Melanocytes, RNA, Messenger
Abstract

Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin.

Published
2006

26. Recessive dystrophic epidermolysis bullosa caused by COL7A1 hemizygosity and a missense mutation with complex effects on splicing

Author

Catherine Prost-Squarcioni, Laure Tonasso, M. Heller, Sylvie Bourthoumieu, José E. Mejía, Alain Hovnanian, Matthias Titeux, Sandra Mirval, and Luciné Mejlumian

Subjects
Proband, Male, Collagen Type VII, RNA Splicing, Mutation, Missense, Genes, Recessive, Biology, Exon, Mice, Genetics, medicine, Missense mutation, Animals, Humans, Allele, Gene, Genetics (clinical), Alleles, Cells, Cultured, In Situ Hybridization, Fluorescence, Epidermolysis bullosa dystrophica, medicine.disease, Molecular biology, Epidermolysis Bullosa Dystrophica, Chromosome 3, Child, Preschool, RNA splicing, Female
Abstract

Loss-of-function mutations in the gene encoding type VII collagen, COL7A1, are the molecular basis of the blistering skin disorder, recessive dystrophic epidermolysis bullosa (RDEB). COL7A1 maps to a region of the short arm of chromosome 3 that has been found to be deleted in many types of malignancies. We have characterized the first case of a large genomic deletion in chromosome 3p21.31 that removes COL7A1 entirely in an RDEB patient. This interstitial deletion spans 255 to 520 kb and encompasses 9 to 15 genes, but seems to have no pathological consequences other than RDEB. We show that the second, hemizygous allele of COL7A1 in this patient bears a base substitution within exon 94, c.7245G>A. This translates into an amino acid substitution, p.M2415I, and leads to a complex splicing abnormality that allows marginal levels of functional mRNA and protein to be synthesized. We propose that the leakiness of the splicing defect enables the partial rescue of collagen VII deficiency. This is consistent with the diagnosis of the moderately severe form of RDEB in the proband, at variance with the most severe form, RDEB Hallopeau-Siemens, that would arise from complete collagen VII deficiency. © 2006 Wiley-Liss, Inc.

Published
2006

27. Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B' regulatory subunit

Author

Laurent Baricault, Jean-Marie Darbon, Christine Dozier, Mortaza Bonyadi, Laure Tonasso, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Identité et plasticité tumorale, and Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Signal Transduction, animal structures, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitogen-activated protein kinase kinase, Protein Serine-Threonine Kinases, MESH: Two-Hybrid System Techniques, environment and public health, MESH: Protein-Serine-Threonine Kinases, MAP2K7, Cell Line, 03 medical and health sciences, MESH: Protein Structure, Tertiary, Two-Hybrid System Techniques, MESH: Phosphoprotein Phosphatases, Phosphoprotein Phosphatases, MESH: Protein Binding, Humans, c-Raf, Protein Phosphatase 2, Phosphorylation, 030304 developmental biology, 0303 health sciences, MESH: Humans, MAP kinase kinase kinase, biology, MESH: Phosphorylation, MESH: Protein Phosphatase 2, 030302 biochemistry & molecular biology, Cyclin-dependent kinase 2, Cell Biology, General Medicine, Protein phosphatase 2, MESH: Protein Subunits, 3. Good health, Cell biology, MESH: Cell Line, Protein Structure, Tertiary, enzymes and coenzymes (carbohydrates), Checkpoint Kinase 2, Protein Subunits, Biochemistry, Cyclin-dependent kinase complex, biology.protein, Casein kinase 2, biological phenomena, cell phenomena, and immunity, Protein Binding, Signal Transduction
Abstract

Chk2 is a key player of the DNA damage signalling pathway. To identify new regulators of this kinase, we performed a yeast two-hybrid screen and found that Chk2 associated with the B′ regulatory subunit of protein phosphatase PP2A. In vitro GST-Chk2 pulldowns demonstrated that B′γ isoforms bound to Chk2 with the strongest apparent affinity. This was confirmed in cellulo by co-immunoprecipitation after overexpression of the respective partners in HEK293 cells. The A and C subunits of PP2A were present in the complexes, suggesting that Chk2 was associated with a functionnal PP2A. In vitro kinase assays showed that B′γ3 was a potent Chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of PP2A measured on MAP kinase-phosphorylated myelin basic protein as well as on autophosphorylated Chk2. Finally, we demonstrated that overexpressing B′γ3 in HEK293 suppressed the phosphorylation of Chk2 induced by a genotoxic treatment, suggesting that PP2A may counteract the action of the checkpoint kinase in living cells.

Published
2004
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28. DNA-Based Prenatal Diagnosis of Harlequin Ichthyosis and Characterization of ABCA12 Mutation Consequences

Author

Hiroshi Shimizu, Laure Tonasso, Frederique Jossic, Masashi Akiyama, Alain Hovnanian, James R. McMillan, Kaori Sakai, Matthias Titeux, and Patrick Calvas

Subjects
Male, DNA Mutational Analysis, Molecular Sequence Data, Nonsense mutation, Dermatology, Biology, medicine.disease_cause, Compound heterozygosity, Biochemistry, Mice, Exon, Pregnancy, Prenatal Diagnosis, Sequence Homology, Nucleic Acid, medicine, Animals, Humans, Amino Acid Sequence, ABCA12, Molecular Biology, Genetics, Mutation, Splice site mutation, Base Sequence, Ichthyosis, Infant, Newborn, DNA, Cell Biology, Harlequin Ichthyosis, medicine.disease, biology.protein, ATP-Binding Cassette Transporters, Female, Ichthyosis, Lamellar
Abstract

Until the identification of ABCA12 as the causative gene, prenatal diagnosis (PD) for harlequin ichthyosis (HI) had been performed by electron microscopic observation of fetal skin biopsy samples. We report the first case of HI DNA-based PD. Direct sequence analysis of ABCA12 revealed that the deceased proband was a compound heterozygote for two novel mutations. The maternal nonsense mutation p.Ser1249Term likely leads to nonsense-mediated messenger RNA decay. The paternal mutation c.7436G>A affects the last codon of exon 50 and was expected to be a splice site mutation. For their third pregnancy, the parents requested PD. Direct sequence analysis of fetal genomic DNA from amniotic fluid cells at 17 weeks gestation revealed the fetus was a compound heterozygote for both mutations. The parents requested the pregnancy to be terminated. Analysis of ABCA12 transcripts of cultured keratinocytes from the abortus showed the presence of six abnormally spliced products from the allele carrying the splice site mutation. Four of them lead to premature termination codons whereas the two others produced shortened proteins missing 21 and 31 amino acids from the second ATP-binding cassette. This report provides evidence for residual ABCA12 expression in HI, and demonstrates the efficiency of early DNA-based PD of HI.

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29. Three Severe Cases of EBS Dowling-Meara Caused by Missense and Frameshift Mutations in the Keratin 14 Gene

Author

Yves de Prost, Laure Tonasso, Alain Hovnanian, Sylvie Fraitag, Christine Bodemer, Matthias Titeux, Juliette Mazereeuw-Hautier, Smail Hadj-Rabia, and Catherine Prost

Subjects
Male, Keratin 14, Genetic counseling, Mutation, Missense, Dermatology, Biochemistry, Frameshift mutation, Epidermolysis bullosa simplex, Keratin, Missense mutation, Medicine, Humans, Frameshift Mutation, Molecular Biology, Skin, Genetics, chemistry.chemical_classification, business.industry, Keratin-14, Infant, Cell Biology, medicine.disease, chemistry, Child, Preschool, Epidermolysis Bullosa Simplex, Mutation (genetic algorithm), Keratins, Epidermolysis bullosa, business
Abstract

We report three unrelated patients affected at birth with an unusually severe form of epidermolysis bullosa simplex Dowling-Meara type (EBS-DM) because of mutations in KRT14 encoding keratin 14. Two patients were heterozygous for the previously described p.M119T mutation. The third patient was heterozygous for a novel c.1246delC mutation predicting the replacement of the helix termination peptide and the tail domain by a 25 amino-acid aberrant carboxyterminal sequence. At age 2 years, patients carrying the p.M119T mutation still suffered from severe EBS-DM, whereas the patient harboring the c.1246delC mutation has improved over time. These cases illustrate genotype–phenotype correlations and have implications for genetic counselling of EBS.

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30. Assessing the impact of USER‐treatment on hyRAD capture applied to ancient DNA

Author

Tomasz Suchan, Lorelei Chauvey, Marine Poullet, Laure Tonasso‐Calvière, Stéphanie Schiavinato, Pierre Clavel, Benoit Clavel, Sébastien Lepetz, Andaine Seguin‐Orlando, and Ludovic Orlando

Subjects
Cytosine, Genetics, Animals, Equidae, Horses, Sequence Analysis, DNA, DNA Methylation, DNA, Ancient, Ecology, Evolution, Behavior and Systematics, Biotechnology, DNA Damage
Abstract

Ancient DNA preservation in subfossil specimens provides a unique opportunity to retrieve genetic information from the past. As ancient DNA extracts are generally dominated by molecules originating from environmental microbes, capture techniques are often used to economically retrieve orthologous sequence data at the population scale. Post-mortem DNA damage, especially the deamination of cytosine residues into uracils, also considerably inflates sequence error rates unless ancient DNA extracts are treated with the USER enzymatic mix prior to library construction. While both approaches have recently gained popularity in ancient DNA research, the impact of USER-treatment on capture efficacy still remains untested. In this study, we applied hyRAD capture to eight ancient equine subfossil specimens from France (1st-17th century CE), including horses, donkeys and their first-generation mule hybrids. We found that USER-treatment could reduce capture efficacy and introduce significant experimental bias. It differentially affected the size distribution of on-target templates following capture with two distinct hyRAD probe sets in a manner that was not driven by differences in probe sizes and DNA methylation levels. Finally, we recovered unbalanced proportions of donkey-specific and horse-specific alleles in mule capture sequence data, due to the combined effects of USER-treatment, probe sets and reference bias. Our work demonstrates that while USER-treatment can improve the quality of ancient DNA sequence data, it can also significantly affect hyRAD capture outcomes, introducing bias in the sequence data that is difficult to predict based on simple molecular probe features. Such technical batch effects may prove easier to model and correct for using capture with synthetic probes of controlled sizes and diversity content.

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31. A New Case of Keratin 14 Functional Knockout Causes Severe Recessive EBS and Questions the Haploinsufficiency Model of Naegeli–Franceschetti–Jadassohn Syndrome

Author

Catherine Prost-Squarcioni, Alain Hovnanian, José E. Mejía, Audrey Décha, N. Pironon, Laure Tonasso, Matthias Titeux, and Géraldine Gasc

Subjects
chemistry.chemical_classification, Pathology, medicine.medical_specialty, Ectodermal dysplasia, Keratin 14, business.industry, Naegeli–Franceschetti–Jadassohn syndrome, Cell Biology, Dermatology, medicine.disease, Biochemistry, Keratin 5, Epidermolysis bullosa simplex, chemistry, Keratin, medicine, Haploinsufficiency, Keratoderma, business, Molecular Biology
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32. EVOSHEEP Project. First zootechnical innovations in Southwest Asian societies (6th–1rst millennia B.C.): Origin and development of sheep breeds

Author

Emmanuelle Vila, Philippe Abrahami, Moussab Al Besso, Rémy Berthon, Frédéric Boyer, Catherine Breniquet, Dan Bradley, Jwana Chahoud, Thomas CUCCHI, Gilles Escarguel, Lionel Gourichon, Huangfu, W., Daniel Helmer, Jamet, H., Joséphine Lesur, Marjan Mashkour, Xavier Matta, Cécile Michel, Azadeh Mohaseb, Bruno Morandière, Ludovic Orlando, Stéphanie Pompanon F., Laure Tonasso-Calvière, Catherine Thèves, Manon Vuillien, ARCHEORIENT - Environnements et sociétés de l'Orient ancien (Archéorient), Université Lumière - Lyon 2 (UL2)-Centre National de la Recherche Scientifique (CNRS), Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre d'Histoire 'Espaces et Cultures' (CHEC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Lebanese University [Beirut] (LU), Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Gestion des ressources naturelles , environnements et sociétés (GReNES), Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE ), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Histoire et Archéologie de l'Orient Cunéiforme (HAROC), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Section for GeoGenetics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE27-0004,EVOSHEEP,Exploration des premières innovations zootechniques dans les sociétés du sud-ouest asiatique (5e-1er millénaires av. J.-C.)(2017), Centre National de la Recherche Scientifique (CNRS)-Université Paul-Valéry - Montpellier 3 (UPVM)-Ministère de la Culture (MC), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE ), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Archéologie des Sociétés Méditerranéennes, Université Paul-Valéry - Montpellier 3 (UM3)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paul-Valéry - Montpellier 3 (UM3)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UM3)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Robotique Et Vivant (ReV), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - Faculté des Sciences et des Techniques, Lebanese University [Beirut], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE), GRENES, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie Moléculaire de Grenoble (ICMG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Université Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Institut national de recherches archéologiques préventives (Inrap)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
breeds, 1rst, sheep, Asian, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, 6th, Southwend, B-C, innovations, Origin, societies, millennia, EVOSHEEP, zootechnical, First, development, ComputingMilieux_MISCELLANEOUS
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