Stéphane NICOLAS

Genomics of the maize genetic diversity

     
  • Genome-Wide Association Mapping
  • Genetic diversity
  • Copy Number Variation
  • High-Throughput Genotyping
  • Linkage Disequilibrium
  • Haplotype
  • Pre-breeding

 INRAE, Junior Investigator

 stephane.nicolas@inrae.fr —   +33 (0)1 69 33 23 69


 Quantitative Genetics and Plant Breeding Methodology

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 Publications      

  • Génétique Quantitative et Évolution - Le Moulon
  • Université Paris-Saclay, INRAE, CNRS, AgroParisTech
  • IDEEV
  • 12 route 128
  • 91190 Gif-sur-Yvette
Stéphane NICOLAS

Education and Positions

  • 2009-Present: INRAe Researcher, Génétique Quantitative et Évolution-Le Moulon, Gif-sur-Yvette, France
  • 2007-2009: Post-doctoratal Fellow on “Fine mapping of linkage disequilibrium in grapevine”, AGAP, Montpelier, France
  • 2007: Phd in Biology and Agriculture Plant Breeding and Genetics, Université Rennes 1 and Agrocampus Ouest, Rennes, France
  • 2003-2007: Phd student on “Genetic control of homeologous recombination in haploid Oilseed Rape (Brassica napus L.)”, IGEPP (formely UMR Amélioration des Plantes et Biotechnologies Végétales), Rennes, France
  • 2003: MsC in Agricultural science (major Plant Genetics and Breeding), AgroCampus Ouest, (formerly École Nationale Supérieure Agronomique de Rennes) and Master Degree in Plant Biology (Seeds and Plants), Université Rennes 1.

Research Interests

Broadening the genetic diversity of the breeding programs by mining interesting allelic variation from the genetic resources is a key issue to speed up the genetic progress, to face the challenge of climate changes, and to decrease the use of fertilizers and pesticides. However, the exploitation of the genetic diversity in breeding programs is currently limited by the poor characterization of germplasms and by the difficulties to identify favorable alleles to improve agronomic traits of elite material. My research aims at overcoming these bottlenecks by better understanding (i) how the DNA polymorphisms contributed to agronomic trait variation, (ii) how the complex interplay between human/environmental selection and other evolutionary forces shaped the genetic diversity along the genome. Maize is a particularly good model to address these questions. Domesticated in Mexico around 9000 years ago, this tropical annual allogamous cereal with high degree of polymorphisms has been selected by humans to grown in various agro-climatic conditions and for various uses until becoming one of the largest cultivated cereal in the world playing an essential role in the food safety.

In this context, I am more particularly interested in:

  1. Deciphering the organization of the genetic diversity within the maize germplasm at the genome scale level and identifying interesting sources of genetic diversity for pre-breeding. My research are focusing on (i) the effect of the modern selection on the genetic diversity and linkage disequilibrium (transition from open pollinated varieties (landraces) to F1 hybrids…) by developing and implementing high-throughput sequencing and genotyping technologies and methods for studying landraces and inbred lines collection, (ii) the detection of genomic regions involved in the adaptation of maize to contrasted environments by integrating selective footprints detection with association studies.

  2. Identifying the allelic variation involved in the variation of agronomic traits and in adaptation to different stress within inbred lines collection representing large genetic diversity using genome-wide association studies (GWAS). My research are focusing on (i) the development and implementation of high-throughput genotyping technologies, methods, and bio-informatics tools for performing GWAS, (ii) the effect of different biological parameters on the power of GWAS for detecting Quantitative Trait Loci, (iii) the development of integrative approaches coupling eco-physiology, GWAS, and functional genomics for identifying allelic variation involved in genotype by environment interaction ().

  3. Studying the contribution of the Copy Number Variations (CNV), e.g changes in gene content and order between inbred lines, to the genetic diversity, the variation of agronomic traits, the adaptation to environment and heterosis. To this end, I develop high-throughput genotyping approaches of these polymorphisms and appropriate statistical methods for genome-wide association studies.

Main current collaborations

  • Lab’s: M. Tenaillon, J. Joets and C. Vitte (GEvAD) ; Y. De Oliviera (BiOSS) ; M. Zivy & M. Blein-Nicolas (PAPPSO-BASE)

  • France: R. Chapuis, F. Meunier (UE Diascope) ; Carine Palaffre (UE SMH) F. Tardieu and C. Welcker (LEPSE) ; P. Faivre-Rampant and D. Hinsinger (EPGV), B. Gouesnard, P. Teres, M. Ecarnot (AGAP) ; M. Raymond, S. Coursol, B. Alunni (IJPB) ; C. Giauffret (UR AgroImpact); C. Maurel (BPMP), T. Farraut, C. Klopp (GenoToul)

  • International: X. Draye and F. Chaumont (UCLouvain), C. Hermans (ULB), R. Ridaelli and C. Balconi (CREA), E. Frascaroli (UNIBO),P. Revilla and R. Ana-Malvar and A. Butron (CSIC), S. Erdal (BATEM), S. Earne (CIMMYT), T. Altman (IPK), V. Andjelkovic (MRIZP), S. Goritschnig (ECPGR)

Teaching / Training

Phd Student / Postdoctoral Fellowship / Short Term Contract

  • Raphaël Minguella (Short-term contract MineLandDiv 2024-Present)
  • Sana Beji (Dromamed and C4Future Post-doctoral fellow 2023-Present)
  • Agustin Galaretto-Oscar (Phd Student 2022-Present)
  • Camille Clipet (Short-term contract 2017-2019)
  • Clément Mabire (Phd Student 2016-2019)
  • Sandra Negro (Drops and Amaizing Post-doctoral fellow : 2013-2017)
  • Mariangela Arca (Diversity Zea and Amaizing Post-doctocal fellow : 2012-2014).

Teaching and training:

  • Genome-Wide Association Mapping (Msc / Master degree in Plant Breeding and Genetics at AgroCampus Ouest, Master 2 at Université Paris Sud, Breeder’s training)

Main responsibilities in recent projects

  • 2024-Present: Principal Investigator of ECPGR project MALANIRs
  • 2022-Present: Principal Investigator of SusCrop EraNet project MineLandDiv
  • 2020-2024: Contributors to ECPGR project EVA Maize (PI: S. Goritschnig): In charge of genotyping and diversity analysis
  • 2021-2024: Contributors to Prima European project Dromamed: (PI: P. Revilla): In charge of diversity, genotyping and GWAS analysis
  • 2020-2023: Project SeqOccin (https://get.genotoul.fr/seqoccin/): Contribution to maize lines sequencing at low depht
  • 2020-2024: SusCrop Eranet project C4Future (PI: C. Hermanns): In charge of maize genotyping, diversity and GWAS analysis
  • 2010-2021: Investissement d’avenir Amaizing (PI: A. Charcosset): Task leader of “high density genotyping and imputation” in WP4 (Lead by L. Moreau)
  • 2016-2019: Co-Principal Investigator with D. Rocha of CNV4Sel INRA Project in the framework of “Métaprogramme SelGen”: “Strategies for CNV discovery in animal and plant species and their use in breeding”
  • 2010-2015: European project F7P Drops (PI: F. Tardieu): In charge of high-throughput genotyping of maize association panel, diversity analysis and development of single environment GWAS approach
  • 2011-2015: PLANT-KBBE European project CornFed (PI: A. Charcosset): In charge of genotyping, GWAS and LD analysis
  • 2011-2015: ANR project GNPasso (PI. D. Steinbach): “Sofware to visualize GWAS results and connect with genome-browser”
  • 2010-2014: Principal Investigator of ANR project CNV-Maize: “Genome wide association study between structural variation, agronomic traits variation and heterosis in maize”
  • 2009-2013: Project Promais Diversity Zea (PI: A. Charcosset), In charge of analysis of genetic diversity landraces using 50K high-troughput genotyping array.

Publications

  • Ali B., Huguenin-Bizot B., Laurent M., Chaumont F., Maistriaux LC., Nicolas S. , Duborjal H., Welcker C., Tardieu F., Mary-Huard T., Moreau L., Charcosset A., Runcie D., Rincent R.. (2024) High-dimensional multi-omics measured in controlled conditions are useful for maize platform and field trait predictions. Theor Appl Genet, 7 (137) 175
  • Balconi C., Galaretto A., Malvar RA., Nicolas S. , Redaelli R., Andjelkovic V., Revilla P., Bauland C., Gouesnard B., Butron A., Torri A., Barata AM., Kravic N., Combes V., Mendes-Moreira P., Murariu D., Šarčević H., Schierscher-Viret B., Vincent M., Zanetto A., Kessel B., Madur D., Mary-Huard T., Pereira A., Placinta DD., Strigens A., Charcosset A., Goritschnig S.. (2024) Genetic and Phenotypic Evaluation of European Maize Landraces as a Tool for Conservation and Valorization of Agrobiodiversity. Biology, 6 (13) 454
  • Maistriaux LC., Laurent MJ., Jeanguenin L., Prado SA., Nader J., Welcker C., Charcosset A., Tardieu F., Nicolas S. , Chaumont F.. (2024) Genetic variability of aquaporin expression in maize: From eQTLs to a MITE insertion regulating PIP2;5 expression. Plant Physiology, kiae326
  • Arca M., Gouesnard B., Mary‐Huard T., Le Paslier MC., Bauland C., Combes V., Madur D., Charcosset A., Nicolas S. . (2023) Genotyping of DNA pools identifies untapped landraces and genomic regions to develop next‐generation varieties. Plant Biotechnology Journal, 6 (21) 1123-1139
  • De Walsche A., Vergne A., Rincent R., Roux F., Nicolas S. , Welcker C., Mezmouk S., Charcosset A., Mary-Huard T.. (2023) metaGE: Investigating Genotype × Environment interactions through meta-analysis. ,
  • Galić V., Anđelković V., Kravić N., Grčić N., Ledenčan T., Jambrović A., Zdunić Z., Nicolas S. , Charcosset A., Šatović Z., Šimić D.. (2023) Genetic diversity and selection signatures in a gene bank panel of maize inbred lines from Southeast Europe compared with two West European panels. BMC Plant Biol, 1 (23) 315
  • Sanane I., Nicolas S. , Bauland C., Marion-Poll F., Noûs C., Legrand J., Dillmann C.. (2023) Large genetic variability of maize leaf palatability to european corn borer : metabolic insights. bioRxiv,
  • Arca M., Mary-Huard T., Gouesnard B., Bérard A., Bauland C., Combes V., Madur D., Charcosset A., Nicolas S. . (2021) Deciphering the Genetic Diversity of Landraces With High-Throughput SNP Genotyping of DNA Bulks: Methodology and Application to the Maize 50k Array. Front. Plant Sci., (11) 568699
  • Diaw Y., Tollon-Cordet C., Charcosset A., Nicolas S. , Madur D., Ronfort J., David J., Gouesnard B., Chiang TY.. (2021) Genetic diversity of maize landraces from the South-West of France. PLoS ONE, 2 (16) e0238334
  • Arca M., Gouesnard B., Mary-Huard T., Le Paslier MC., Bauland C., Combes V., Madur D., Charcosset A., Nicolas S. . (2020) Genome-wide SNP genotyping of DNA pools identifies untapped landraces and genomic regions that could enrich the maize breeding pool. DOI.org (Crossref),
  • Blein-Nicolas M., Negro SS., Balliau T., Welcker C., Cabrera-Bosquet L., Nicolas S. , Charcosset A., Zivy M.. (2020) A systems genetics approach reveals environment-dependent associations between SNPs, protein coexpression, and drought-related traits in maize. Genome Res., 11 (30) 1593-1604
  • Castelletti S., Coupel-Ledru A., Granato I., Palaffre C., Cabrera-Bosquet L., Tonelli C., Nicolas S. , Tardieu F., Welcker C., Conti L., de Meaux J.. (2020) Maize adaptation across temperate climates was obtained via expression of two florigen genes. PLoS Genet, 7 (16) e1008882
  • Mabire C., 2019-04, Contribution des variations structurales de type insertions/délétions à l'adaptation, la variation des caractères et les performances hybrides chez le maïs, Theses, Université Paris Saclay (COmUE)
  • Mabire C., Duarte J., Darracq A., Pirani A., Rimbert H., Madur D., Combes V., Vitte C., Praud S., Rivière N., Joets J., Pichon JP., Nicolas S. . (2019) High throughput genotyping of structural variations in a complex plant genome using an original Affymetrix® axiom® array. BMC Genomics, 1 (20) 848
  • Negro SS., Millet EJ., Madur D., Bauland C., Combes V., Welcker C., Tardieu F., Charcosset A., Nicolas S. . (2019) Genotyping-by-sequencing and SNP-arrays are complementary for detecting quantitative trait loci by tagging different haplotypes in association studies. BMC Plant Biol., 1 (19) 318
  • Darracq A., Vitte C., Nicolas S. , Duarte J., Pichon JP., Mary-Huard T., Chevalier C., Bérard A., Le Paslier MC., Rogowsky P., Charcosset A., Joets J.. (2018) Sequence analysis of European maize inbred line F2 provides new insights into molecular and chromosomal characteristics of presence/absence variants. BMC Genomics, 1 (19) 119
  • Brandenburg JT., Mary-Huard T., Rigaill G., Hearne SJ., Corti H., Joets J., Vitte C., Charcosset A., Nicolas S. , Tenaillon MI.. (2017) Independent introductions and admixtures have contributed to adaptation of European maize and its American counterparts. PLOS Genetics, 3 (13) e1006666
  • Cañas RA., Yesbergenova-Cuny Z., Simons M., Chardon F., Armengaud P., Quilleré I., Cukier C., Gibon Y., Limami AM., Nicolas S. , Brulé L., Lea PJ., Maranas CD., Hirel B.. (2017) Exploiting the Genetic Diversity of Maize Using a Combined Metabolomic, Enzyme Activity Profiling, and Metabolic Modeling Approach to Link Leaf Physiology to Kernel Yield. The Plant Cell, 5 (29) 919-943
  • Gouesnard B., Negro S., Laffray A., Glaubitz J., Melchinger A., Revilla P., Moreno-Gonzalez J., Madur D., Combes V., Tollon-Cordet C., Laborde J., Kermarrec D., Bauland C., Moreau L., Charcosset A., Nicolas S. . (2017) Genotyping-by-sequencing highlights original diversity patterns within a European collection of 1191 maize flint lines, as compared to the maize USDA genebank. Theor Appl Genet, 10 (130) 2165-2189
  • Millet E., Welcker C., Kruijer W., Negro S., Nicolas S. , Coupel-Ledru A., Bauland C., Praud S., Ranc N., Presterl T., Tuberosa R., Bedo Z., Draye X., Usadel B., Charcosset A., van Eeuwijk F., Tardieu F.. (2016) Genome-wide analysis of yield in Europe: allelic effects as functions of drought and heat scenarios. Plant physiology, 2 (172) 749-764
  • Nicolas S. , Peros JP., Lacombe T., Launay A., Le Paslier MC., Berard A., Mangin B., Valiere S., Martins F., Le Cunff L., Laucou V., Bacilieri R., Dereeper A., Chatelet P., This P., Doligez A.. (2016) Genetic diversity, linkage disequilibrium and power of a large grapevine (Vitis vinifera L) diversity panel newly designed for association studies. BMC plant biology, 1 (16) 74
  • Tenaillon MI., Manicacci D., Nicolas S. , Tardieu F., Welcker C.. (2016) Testing the link between genome size and growth rate in maize. PeerJ, (4) e2408
  • Rincent R., Nicolas S. , Bouchet S., Altmann T., Brunel D., Revilla P., Malvar RA., Moreno-Gonzalez J., Campo L., Melchinger AE., Schipprack W., Bauer E., Schoen CC., Meyer N., Ouzunova M., Dubreuil P., Giauffret C., Madur D., Combes V., Dumas F., Bauland C., Jamin P., Laborde J., Flament P., Moreau L., Charcosset A.. (2014) Dent and Flint maize diversity panels reveal important genetic potential for increasing biomass production. Theor Appl Genet, 11 (127) 2313-31
  • Rincent R., Moreau L., Monod H., Kuhn E., Melchinger AE., Malvar RA., Moreno-Gonzalez J., Nicolas S. , Madur D., Combes V., Dumas F., Altmann T., Brunel D., Ouzunova M., Flament P., Dubreuil P., Charcosset A., Mary-Huard T.. (2014) Recovering power in association mapping panels with variable levels of linkage disequilibrium. Genetics, 1 (197) 375-87
  • Bouchet S., Servin B., Bertin P., Madur D., Combes V., Dumas F., Brunel D., Laborde J., Charcosset A., Nicolas S. . (2013) Adaptation of maize to temperate climates: mid-density genome-wide association genetics and diversity patterns reveal key genomic regions, with a major contribution of the Vgt2 (ZCN8) locus. PloS one, 8 (8) e71377
  • Houel C., Martin-Magniette ML., Nicolas S. , Lacombe T., Le Cunff L., Franck D., Torregrosa L., Conéjéro G., Lalet S., This P., Adam-Blondon AF.. (2013) Genetic diversity of berry size in grapevine (Vitis vinifera L.). Aus J Grape and Wine R, 2 (19) 208-220
  • Mangin B., Siberchicot A., Nicolas S. , Doligez A., This P., Cierco-Ayrolles C.. (2012) Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness. Heredity, 3 (108) 285-91
  • Nicolas S. , Monod H., Eber F., Chevre AM., Jenczewski E.. (2012) Non-random distribution of extensive chromosome rearrangements in Brassica napus depends on genome organization. The Plant journal : for cell and molecular biology, 4 (70) 691-703
  • Rincent R., Laloe D., Nicolas S. , Altmann T., Brunel D., Revilla P., Rodriguez VM., Moreno-Gonzalez J., Melchinger A., Bauer E., Schoen CC., Meyer N., Giauffret C., Bauland C., Jamin P., Laborde J., Monod H., Flament P., Charcosset A., Moreau L.. (2012) Maximizing the reliability of genomic selection by optimizing the calibration set of reference individuals: comparison of methods in two diverse groups of maize inbreds (Zea mays L.). Genetics, 2 (192) 715-28
  • Truntzler M., Ranc N., Sawkins MC., Nicolas S. , Manicacci D., Lespinasse D., Ribiere V., Galaup P., Servant F., Muller C., Madur D., Betran J., Charcosset A., Moreau L.. (2012) Diversity and linkage disequilibrium features in a composite public/private dent maize panel: consequences for association genetics as evaluated from a case study using flowering time. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik, 4 (125) 731-47
  • Dereeper A., Nicolas S. , Le Cunff L., Bacilieri R., Doligez A., Peros JP., Ruiz M., This P.. (2011) SNiPlay: a web-based tool for detection, management and analysis of SNPs. Application to grapevine diversity projects. BMC bioinformatics, (12) 134
  • Nicolas S. , Leflon M., Monod H., Eber F., Coriton O., Huteau V., Chevre AM., Jenczewski E.. (2009) Genetic regulation of meiotic cross-overs between related genomes in Brassica napus haploids and hybrids. The Plant cell, 2 (21) 373-85