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Génétique Quantitative et Évolution - Le Moulon

Stéphane NICOLAS

Stéphane NICOLAS

Junior Investigator, INRAE

Genomics of the maize genetic diversity

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


+33 (0)1 69 33 23 69



  • Génétique Quantitative et Évolution - Le Moulon
  • Université Paris-Saclay, INRAE, CNRS, AgroParisTech
  • Ferme du Moulon
  • F-91190 Gif-sur-Yvette

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 & C. Vitte (DyGAP) ; D. Steinbach, Y. De Oliviera & P. Montalent (ABI) ; M. Zivy & M. Blein-Nicolas (PAPPSO)

  • France: F. Tardieu and C. Welcker (LEPSE) ; M-C Le Paslier (EPGV), B. Gouesnard and A. Doligez (AGAP) ; S. Robin, E. Lebarbier and J. Aubert (MIA) ; P. Dubreuil, J-P Pichon, S. Praud, M-H Tixier and J. Duarte (Biogemma) ; B. Hirel, M. Raymond and S. Coursol (IJPB) ; C. Giauffret (UR AgroImpact) ; B. Mangin (Toulouse)

  • International: F. Van Eeuwick, W. Kruijer (Wageningen University), F. Chaumont (UCL).

Teaching / Training

Phd Student / Postdoctoral Fellowship / CDD

  • Clément Mabire (Phd Student 2016-2019)
  • Camille Clipet (2017-2019)
  • 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)
  • Linkage disequilibrium (Master degree GCDE & Doctoral School GGC).

Main responsibilities in recent projects

  • 2010-Present: 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.


Arca M, Mary-Huard T, Gouesnard B, Bérard A, Bauland C, Combes V, Madur D, Charcosset A, Nicolas SD. (2020) Deciphering the genetic diversity of landraces with high-throughput SNP genotyping of DNA bulks: methodology and application to the maize 50k array. bioRxiv,
Castelletti S, Coupel-Ledru A, Granato I, Palaffre C, Cabrera-Bosquet L, Tonelli C, Nicolas SD, 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, 2019-04-23 23/04/19, Contribution des variations structurales de type insertions/délétions à l'adaptation, la variation des caractères et les performances hybrides chez le maïs
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 SD. (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 SD. (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 SD, 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
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 SD, 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 SD, Tardieu F, Welcker C. (2016) Testing the link between genome size and growth rate in maize. PeerJ, (4) e2408
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
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
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 SD, 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 SD, 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