Genetics, Genomics and Metabolomics

Metabolomics approaches enable the parallel assessment of the levels of a broad range of metabolites. They have been documented to have great value in phenotyping and diagnostic analyses in plants as well as showing great promise as a tool for bio-prospecting novel pharmaceuticals. These tools have recently been turned to evaluation of the natural variance apparent in metabolite composition both in the model species Arabidopsis thaliana and a range of crop species. Here, we describe exciting progress made in the identification of the genetic determinants of plant chemical composition, focusing on the application of various different metabolomics strategies. We focus on the integration of these data with those other high-throughput technologies and discuss the value of such approaches for gaining fundamental insights into metabolic and even cellular regulation. Finally, we discuss the fact that when considered from an applied perspective metabolomics represents an important addition to the tools currently employed in genomicsassisted selection for crop improvement

[1]  Six new recombinant inbred populations for the study of quantitative traits in Arabidopsis thaliana , 2008, Theoretical and Applied Genetics.

[2]  A. Fernie,et al.  Journal of Experimental Botany, Page 1 of 11 Metabolomics and Metabolic Profiling Special Issue , 2004 .

[3]  A. Fernie,et al.  Natural genetic variation for improving crop quality. , 2006, Current opinion in plant biology.

[4]  R. Canales,et al.  Plant nuclear factor Y (NF-Y) B subunits confer drought tolerance and lead to improved corn yields on water-limited acres , 2007, Proceedings of the National Academy of Sciences.

[5]  W. Weckwerth,et al.  Metabolite profiling in plant biology: platforms and destinations , 2004, Genome Biology.

[6]  G. Coupland,et al.  Analysis of natural allelic variation at flowering time loci in the Landsberg erecta and Cape Verde Islands ecotypes of Arabidopsis thaliana. , 1998, Genetics.

[7]  Detlef Weigel,et al.  QTL Mapping in New Arabidopsis thaliana Advanced Intercross-Recombinant Inbred Lines , 2009, PloS one.

[8]  O. Fiehn,et al.  Metabolite profiling for plant functional genomics , 2000, Nature Biotechnology.

[9]  Thomas Altmann,et al.  Description and applications of a rapid and sensitive non-radioactive microplate-based assay for maximum and initial activity of D-ribulose-1,5-bisphosphate carboxylase/oxygenase. , 2007, Plant, cell & environment.

[10]  E. Pichersky,et al.  Metabolomics, genomics, proteomics, and the identification of enzymes and their substrates and products. , 2005, Current opinion in plant biology.

[11]  Bin Han,et al.  GS3, a major QTL for grain length and weight and minor QTL for grain width and thickness in rice, encodes a putative transmembrane protein , 2006, Theoretical and Applied Genetics.

[12]  Graham J King,et al.  A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening , 2006, Nature Genetics.

[13]  Kirk A. Stowe,et al.  Identification and characterization of QTL underlying whole‐plant physiology in Arabidopsis thaliana: δ13C, stomatal conductance and transpiration efficiency , 2005 .

[14]  G. Slafer,et al.  Agronomy and plant breeding are key to combating food crisis , 2008, Nature.

[15]  Fabio Fornara,et al.  FT Protein Movement Contributes to Long-Distance Signaling in Floral Induction of Arabidopsis , 2007, Science.

[16]  J. Gershenzon,et al.  Genetic control of natural variation in Arabidopsis glucosinolate accumulation. , 2001, Plant physiology.

[17]  E. Septiningsih,et al.  Identification of quantitative trait loci for yield and yield components in an advanced backcross population derived from the Oryza sativa variety IR64 and the wild relative O. rufipogon , 2003, Theoretical and Applied Genetics.

[18]  J. Keurentjes,et al.  Vacuolar invertase regulates elongation of Arabidopsis thaliana roots as revealed by QTL and mutant analysis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[19]  P. Karlovsky,et al.  Relationship between metabolic and genomic diversity in sesame (Sesamum indicum L.) , 2008, BMC Genomics.

[20]  Jianbing Yan,et al.  Natural Genetic Variation in Lycopene Epsilon Cyclase Tapped for Maize Biofortification , 2008, Science.

[21]  S. Kanaya,et al.  Summary , 1940, Intellectual Property in the Conflict of Laws.

[22]  R W Doerge,et al.  Genomic Survey of Gene Expression Diversity in Arabidopsis thaliana , 2006, Genetics.

[23]  Chris Somerville,et al.  Plant Biology in 2010 , 2000, Science.

[24]  Wayne E. Brown,et al.  Impact of genetics and environment on nutritional and metabolite components of maize grain. , 2007, Journal of agricultural and food chemistry.

[25]  A. Fernie,et al.  Metabolite profiling: from diagnostics to systems biology , 2004, Nature Reviews Molecular Cell Biology.

[26]  T. Mitchell-Olds,et al.  Genetic mechanisms and evolutionary significance of natural variation in Arabidopsis , 2006, Nature.

[27]  R. Chetelat,et al.  A library of Solanum lycopersicoides introgression lines in cultivated tomato. , 2005, Genome.

[28]  T. Fujiwara,et al.  Arabidopsis boron transporter for xylem loading , 2002, Nature.

[29]  J. O. Mora.  Proposed vitamin a fortification levels. , 2003, The Journal of nutrition.

[30]  A. Powell,et al.  QTL analysis of fruit antioxidants in tomato using Lycopersicon pennellii introgression lines , 2005, Theoretical and Applied Genetics.

[31]  Fei Zou,et al.  Quantitative Trait Locus Analysis Using Recombinant Inbred Intercrosses , 2005, Genetics.

[32]  H. Kanamori,et al.  Barley grain with adhering hulls is controlled by an ERF family transcription factor gene regulating a lipid biosynthesis pathway , 2008, Proceedings of the National Academy of Sciences.

[33]  Lothar Willmitzer,et al.  High-resolution direct infusion-based mass spectrometry in combination with whole 13C metabolome isotope labeling allows unambiguous assignment of chemical sum formulas. , 2008, Analytical chemistry.

[34]  J. Selbig,et al.  Mode of Inheritance of Primary Metabolic Traits in Tomato[W][OA] , 2008, The Plant Cell Online.

[35]  K. Koch,et al.  Sucrose metabolism: regulatory mechanisms and pivotal roles in sugar sensing and plant development. , 2004, Current opinion in plant biology.

[36]  S. Schuster.  Next-generation sequencing transforms today's biology , 2008, Nature Methods.

[37]  Daniel J. Kliebenstein,et al.  Linking Metabolic QTLs with Network and cis-eQTLs Controlling Biosynthetic Pathways , 2007, PLoS genetics.

[38]  C. Gebhardt,et al.  Plant genome analysis: the state of the art. , 2005, International review of cytology.

[39]  O. Loudet,et al.  Natural variation for sulfate content in Arabidopsis thaliana is highly controlled by APR2 , 2007, Nature Genetics.

[40]  Wei Huang,et al.  A QTL for rice grain width and weight encodes a previously unknown RING-type E3 ubiquitin ligase , 2007, Nature Genetics.

[41]  Mark Stitt,et al.  From measurements of metabolites to metabolomics: an 'on the fly' perspective illustrated by recent studies of carbon-nitrogen interactions. , 2003, Current opinion in biotechnology.

[42]  O. Jeong,et al.  Mapping quantitative trait loci for yield components and morphological traits in an advanced backcross population between Oryza grandiglumis and the O. sativa japonica cultivar Hwaseongbyeo , 2006, Theoretical and Applied Genetics.

[43]  F. Carrari,et al.  Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. , 2004, Current opinion in plant biology.

[44]  Geert Plaetinck,et al.  Control of coleopteran insect pests through RNA interference , 2007, Nature Biotechnology.

[45]  M. Matsuoka,et al.  Genetic approaches to crop improvement: responding to environmental and population changes , 2008, Nature Reviews Genetics.

[46]  G. Martin,et al.  Transcriptome and Selected Metabolite Analyses Reveal Multiple Points of Ethylene Control during Tomato Fruit Developmentw⃞ , 2005, The Plant Cell Online.

[47]  Alisdair R Fernie,et al.  Tomato aromatic amino acid decarboxylases participate in synthesis of the flavor volatiles 2-phenylethanol and 2-phenylacetaldehyde. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[48]  U. Roessner,et al.  Comprehensive metabolic profiling and phenotyping of interspecific introgression lines for tomato improvement , 2006, Nature Biotechnology.

[49]  R. Dixon,et al.  Metabolomics Reveals Novel Pathways and Differential Mechanistic and Elicitor-Specific Responses in Phenylpropanoid and Isoflavonoid Biosynthesis in Medicago truncatula Cell Cultures1[C][W][OA] , 2007, Plant Physiology.

[50]  D. Schomburg,et al.  GC–MS libraries for the rapid identification of metabolites in complex biological samples , 2005, FEBS letters.

[51]  D. Zamir.  Improving plant breeding with exotic genetic libraries , 2001, Nature Reviews Genetics.

[52]  Olivier Loudet,et al.  Identification of QTL controlling root growth response to phosphate starvation in Arabidopsis thaliana. , 2006, Plant, cell & environment.

[53]  Oliver Fiehn,et al.  Systems Rebalancing of Metabolism in Response to Sulfur Deprivation, as Revealed by Metabolome Analysis of Arabidopsis Plants1[w] , 2005, Plant Physiology.

[54]  E. Buckler,et al.  Genetic association mapping and genome organization of maize. , 2006, Current opinion in biotechnology.

[55]  Joachim Selbig,et al.  The metabolic signature related to high plant growth rate in Arabidopsis thaliana , 2007, Proceedings of the National Academy of Sciences.

[56]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[57]  Wayne E. Brown,et al.  Metabolite analyses of grain from maize hybrids grown in the United States under drought and watered conditions during the 2002 field season. , 2007, Journal of agricultural and food chemistry.

[58]  Justin O Borevitz,et al.  The Impact of Genomics on the Study of Natural Variation in Arabidopsis , 2003, Plant Physiology.

[59]  David Stoddart,et al.  Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore , 2009, Proceedings of the National Academy of Sciences.

[60]  P. Bliss,et al.  Identification of loci affecting flavour volatile emissions in tomato fruits. , 2006, Journal of experimental botany.

[61]  Aalim M Weljie,et al.  Quantitative 1H Nuclear Magnetic Resonance Metabolite Profiling as a Functional Genomics Platform to Investigate Alkaloid Biosynthesis in Opium Poppy1[W] , 2008, Plant Physiology.

[62]  C. Rameau,et al.  DETERMINATE and LATE FLOWERING Are Two TERMINAL FLOWER1/CENTRORADIALIS Homologs That Control Two Distinct Phases of Flowering Initiation and Development in Pea Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.015701. , 2003, The Plant Cell Online.

[63]  P. Lindhout,et al.  The development of lettuce backcross inbred lines (BILs) for exploitation of the Lactuca saligna (wild lettuce) germplasm , 2004, Theoretical and Applied Genetics.

[64]  M J Varagona,et al.  Alternative splicing induced by insertion of retrotransposons into the maize waxy gene. , 1992, The Plant cell.

[65]  Detlef Weigel,et al.  Regulation and functional specialization of small RNA-target nodes during plant development. , 2009, Current opinion in plant biology.

[66]  J. Keurentjes.  Genetical metabolomics: closing in on phenotypes. , 2009, Current opinion in plant biology.

[67]  J. Keurentjes,et al.  Sucrose-Specific Induction of Anthocyanin Biosynthesis in Arabidopsis Requires the MYB75/PAP1 Gene1 , 2005, Plant Physiology.

[68]  D. Kliebenstein.  Advancing Genetic Theory and Application by Metabolic Quantitative Trait Loci Analysis , 2009, The Plant Cell Online.

[69]  Kazuyuki Doi,et al.  Ehd1, a B-type response regulator in rice, confers short-day promotion of flowering and controls FT-like gene expression independently of Hd1. , 2004, Genes & development.

[70]  L. Yan,et al.  Allelic variation at the VRN-1 promoter region in polyploid wheat , 2004, Theoretical and Applied Genetics.

[71]  J. Chory,et al.  Genomics tools for QTL analysis and gene discovery. , 2004, Current opinion in plant biology.

[72]  M. Yano,et al.  Hd6, a rice quantitative trait locus involved in photoperiod sensitivity, encodes the α subunit of protein kinase CK2 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[73]  Yan Long,et al.  Single nucleotide polymorphism (SNP) discovery in the polyploid Brassica napus using Solexa transcriptome sequencing. , 2009, Plant biotechnology journal.

[74]  R. Jetter,et al.  Identification of the Wax Ester Synthase/Acyl-Coenzyme A:Diacylglycerol Acyltransferase WSD1 Required for Stem Wax Ester Biosynthesis in Arabidopsis12[W][OA] , 2008, Plant Physiology.

[75]  K. Shimamoto,et al.  Simple RNAi vectors for stable and transient suppression of gene function in rice. , 2004, Plant & cell physiology.

[76]  Joachim Selbig,et al.  Starch as a major integrator in the regulation of plant growth , 2009, Proceedings of the National Academy of Sciences.

[77]  F. Salamini,et al.  Plant biotechnology and breeding: allied for years to come. , 2003, Trends in plant science.

[78]  J. Maloof.  QTL for plant growth and morphology. , 2003, Current opinion in plant biology.

[79]  E. Stockinger,et al.  A Retrotransposon-Mediated Gene Duplication Underlies Morphological Variation of Tomato Fruit , 2008, Science.

[80]  M. West,et al.  Marker-assisted introgression of blackmold resistance QTL alleles from wild Lycopersicon cheesmanii to cultivated tomato (L. esculentum) and evaluation of QTL phenotypic effects , 2001, Molecular Breeding.

[81]  S. Wessler,et al.  A naturally occurring functional allele of the rice waxy locus has a GT to TT mutation at the 5' splice site of the first intron. , 1998, The Plant journal : for cell and molecular biology.

[82]  Y. Kamiya,et al.  ELONGATED UPPERMOST INTERNODE Encodes a Cytochrome P450 Monooxygenase That Epoxidizes Gibberellins in a Novel Deactivation Reaction in Rice[W] , 2006, The Plant Cell Online.

[83]  M. Causse,et al.  QTL analysis of fruit quality in fresh market tomato: a few chromosome regions control the variation of sensory and instrumental traits. , 2002, Journal of experimental botany.

[84]  M. Stitt,et al.  Physiology and metabolism: Reacting to the full complexity of metabolic pathways in a postgenomic era , 2004 .

[85]  C. West.  Meeting requirements for vitamin A. , 2009, Nutrition reviews.

[86]  O. Voinnet.  Origin, Biogenesis, and Activity of Plant MicroRNAs , 2009, Cell.

[87]  L. Kruglyak,et al.  Genetics of global gene expression , 2006, Nature Reviews Genetics.

[88]  R. Hogers,et al.  SNPWave: a flexible multiplexed SNP genotyping technology. , 2004, Nucleic acids research.

[89]  J. Meyer,et al.  Introgression of a quantitative trait locus for yield from Glycine soja into commercial soybean cultivars , 2003, Theoretical and Applied Genetics.

[90]  D. Rolin,et al.  The Metabolic Architecture of Plant Cells , 2002, The Journal of Biological Chemistry.

[91]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[92]  M. Koornneef,et al.  Cloning of DOG1, a quantitative trait locus controlling seed dormancy in Arabidopsis , 2006, Proceedings of the National Academy of Sciences.

[93]  J. Léon,et al.  Advanced backcross QTL analysis in barley (Hordeum vulgare L.) , 2003, Theoretical and Applied Genetics.

[94]  M. McMullen,et al.  Genetic Design and Statistical Power of Nested Association Mapping in Maize , 2008, Genetics.

[95]  M. Matsuoka,et al.  Identification, isolation and pyramiding of quantitative trait loci for rice breeding. , 2006, Trends in plant science.

[96]  Detlef Weigel,et al.  Highly Specific Gene Silencing by Artificial miRNAs in Rice , 2008, PloS one.

[97]  Derek Stewart,et al.  CROPS AND TASTY, NUTRITIOUS FOOD - HOW CAN METABOLOMICS HELP? , 2011 .

[98]  O. Loudet,et al.  A Naturally Occurring Mutation in an Arabidopsis Accession Affects a β-d-Galactosidase That Increases the Hydrophilic Potential of Rhamnogalacturonan I in Seed Mucilage[W] , 2007, The Plant Cell Online.

[99]  Jingyuan Fu,et al.  Regulatory network construction in Arabidopsis by using genome-wide gene expression quantitative trait loci , 2007, Proceedings of the National Academy of Sciences.

[100]  C. Tonelli,et al.  Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reperfusion injury. , 2008, The Journal of nutrition.

[101]  Kazuo Shinozaki,et al.  Characterization of the ABA-regulated global responses to dehydration in Arabidopsis by metabolomics. , 2009, The Plant journal : for cell and molecular biology.

[102]  Eric S. Lander,et al.  Genetic Dissection of Complex Traits with Chromosome Substitution Strains of Mice , 2004, Science.

[103]  Masatomo Kobayashi,et al.  The dwarf-1 (dt) Mutant of Zea mays blocks three steps in the gibberellin-biosynthetic pathway. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[104]  R. Jansen.  Quantitative trait loci in inbred lines , 2004 .

[105]  P. Langridge,et al.  Boron-Toxicity Tolerance in Barley Arising from Efflux Transporter Amplification , 2007, Science.

[106]  Henning Redestig,et al.  Metabolome-ionome-biomass interactions , 2008, Plant signaling & behavior.

[107]  Thomas Altmann,et al.  Variation of Enzyme Activities and Metabolite Levels in 24 Arabidopsis Accessions Growing in Carbon-Limited Conditions1[W] , 2006, Plant Physiology.

[108]  D. Zamir,et al.  An introgression line population of Lycopersicon pennellii in the cultivated tomato enables the identification and fine mapping of yield-associated QTL. , 1995, Genetics.

[109]  S. Ullrich,et al.  Fine structure mapping of the barley chromosome-1 centromere region containing malting-quality QTLs , 1997, Theoretical and Applied Genetics.

[110]  S. Jackson,et al.  Next-generation sequencing technologies and their implications for crop genetics and breeding. , 2009, Trends in biotechnology.

[111]  Z. Fei,et al.  Flavour compounds in tomato fruits: identification of loci and potential pathways affecting volatile composition , 2008, Journal of experimental botany.

[112]  J. Keurentjes,et al.  Advances in Genetical Genomics of Plants , 2009, Current genomics.

[113]  Andreas Graner,et al.  Six-rowed barley originated from a mutation in a homeodomain-leucine zipper I-class homeobox gene , 2007, Proceedings of the National Academy of Sciences.

[114]  M. Koornneef,et al.  Naturally occurring genetic variation in Arabidopsis thaliana. , 2004, Annual review of plant biology.

[115]  R. Dixon,et al.  Plant metabolomics: large-scale phytochemistry in the functional genomics era. , 2003, Phytochemistry.

[116]  T. Rocheford,et al.  Dissection of Maize Kernel Composition and Starch Production by Candidate Gene Association , 2004, The Plant Cell Online.

[117]  D. Kliebenstein,et al.  Understanding the Evolution of Defense Metabolites in Arabidopsis thaliana Using Genome-wide Association Mapping , 2010, Genetics.

[118]  M. Nordborg,et al.  Natural Variation in Arabidopsis. How Do We Find the Causal Genes? , 2005, Plant Physiology.

[119]  B. Underwood.  Vitamin A deficiency disorders: international efforts to control a preventable "pox". , 2004, The Journal of nutrition.

[120]  C. Hardtke,et al.  Natural genetic variation in Arabidopsis identifies BREVIS RADIX , a novel regulator of cell proliferation and elongation in the root , 2004 .

[121]  Bjarne Gram Hansen,et al.  Biochemical Networks and Epistasis Shape the Arabidopsis thaliana Metabolome[W] , 2008, The Plant Cell Online.

[122]  J. Keurentjes,et al.  Development of a Near-Isogenic Line Population of Arabidopsis thaliana and Comparison of Mapping Power With a Recombinant Inbred Line Population , 2007, Genetics.

[123]  M. Zanor,et al.  RNA Interference of LIN5 in Tomato Confirms Its Role in Controlling Brix Content, Uncovers the Influence of Sugars on the Levels of Fruit Hormones, and Demonstrates the Importance of Sucrose Cleavage for Normal Fruit Development and Fertility1[W][OA] , 2009, Plant Physiology.

[124]  Joachim Selbig,et al.  Identification of heterotic metabolite QTL in Arabidopsis thaliana RIL and IL populations. , 2009, The Plant journal : for cell and molecular biology.

[125]  S. Luan,et al.  A rice quantitative trait locus for salt tolerance encodes a sodium transporter , 2005, Nature Genetics.

[126]  N. Leonhardt,et al.  A Novel Pathway for Sesquiterpene Biosynthesis from Z,Z-Farnesyl Pyrophosphate in the Wild Tomato Solanum habrochaites[W] , 2009, The Plant Cell Online.

[127]  E. Pichersky,et al.  Genetics and biochemistry of secondary metabolites in plants: an evolutionary perspective. , 2000, Trends in plant science.

[128]  D. Inzé,et al.  A functional genomics approach toward the understanding of secondary metabolism in plant cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[129]  T. C. Nesbitt,et al.  fw2.2: a quantitative trait locus key to the evolution of tomato fruit size. , 2000, Science.

[130]  D. Kliebenstein.  Quantitative genomics: analyzing intraspecific variation using global gene expression polymorphisms or eQTLs. , 2009, Annual review of plant biology.

[131]  Michael R. Sussman,et al.  Metabolomics of Arabidopsis Thaliana , 2011 .

[132]  J. Lupski,et al.  The complete genome of an individual by massively parallel DNA sequencing , 2008, Nature.

[133]  F. Salamini,et al.  Cold sweetening in diploid potato: mapping quantitative trait loci and candidate genes. , 2002, Genetics.

[134]  Andreas Graner,et al.  Genic microsatellite markers in plants: features and applications. , 2005, Trends in biotechnology.

[135]  R. Mithen,et al.  The Inheritance of Aliphatic Glucosinolates in Brassica napus , 1993 .

[136]  Lei Wang,et al.  Natural variation in Ghd7 is an important regulator of heading date and yield potential in rice , 2008, Nature Genetics.

[137]  E. Septiningsih,et al.  Identification of quantitative trait loci for grain quality in an advanced backcross population derived from the Oryza sativa variety IR64 and the wild relative O. rufipogon , 2003, Theoretical and Applied Genetics.

[138]  S. Tanksley,et al.  Fine mapping of quantitative trait loci for improved fruit characteristics from Lycopersicon chmielewskii chromosome 1. , 2003, Genome.

[139]  I. Paran,et al.  Mapping of yield-related QTLs in pepper in an interspecific cross of Capsicum annuum and C. frutescens , 2003, Theoretical and Applied Genetics.

[140]  V. Luca,et al.  The cell and developmental biology of alkaloid biosynthesis , 2000 .

[141]  Kazuki Saito,et al.  Potential of metabolomics as a functional genomics tool. , 2004, Trends in plant science.

[142]  Robert D Hall,et al.  Plant metabolomics and its potential application for human nutrition. , 2007, Physiologia plantarum.

[143]  A. Blanco,et al.  Detection of QTLs for grain protein content in durum wheat , 2006, Theoretical and Applied Genetics.

[144]  Detlef Weigel,et al.  Quantitative trait locus mapping and DNA array hybridization identify an FLM deletion as a cause for natural flowering-time variation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[145]  P. Goldsbrough,et al.  Heterogeneous inbred family (HIF) analysis: a method for developing near-isogenic lines that differ at quantitative trait loci , 1997, Theoretical and Applied Genetics.

[146]  J. Léon,et al.  Development of candidate introgression lines using an exotic barley accession (Hordeum vulgare ssp. spontaneum) as donor , 2004, Theoretical and Applied Genetics.

[147]  Mark Stitt,et al.  Metabolic control analysis and regulation of the conversion of sucrose to starch in growing potato tubers , 2004 .

[148]  R. Lister,et al.  Next is now: new technologies for sequencing of genomes, transcriptomes, and beyond. , 2009, Current opinion in plant biology.

[149]  J. Chory,et al.  Natural variation in light sensitivity of Arabidopsis , 2001, Nature Genetics.

[150]  M. Hirai,et al.  Elucidation of Gene-to-Gene and Metabolite-to-Gene Networks in Arabidopsis by Integration of Metabolomics and Transcriptomics* , 2005, Journal of Biological Chemistry.

[151]  J. Selbig,et al.  Parallel analysis of transcript and metabolic profiles: a new approach in systems biology , 2003, EMBO reports.

[152]  Andrew J. Millar,et al.  Natural Allelic Variation in the Temperature-Compensation Mechanisms of the Arabidopsis thaliana Circadian Clock Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY685131 and AY685132. , 2005, Genetics.

[153]  J. Gershenzon,et al.  The secondary metabolism of Arabidopsis thaliana: growing like a weed. , 2005, Current opinion in plant biology.

[154]  L. Sweetlove,et al.  Comparison of changes in fruit gene expression in tomato introgression lines provides evidence of genome-wide transcriptional changes and reveals links to mapped QTLs and described traits. , 2005, Journal of experimental botany.

[155]  S. Tanksley.  The Genetic, Developmental, and Molecular Bases of Fruit Size and Shape Variation in Tomato , 2004, The Plant Cell Online.

[156]  R. Doerge,et al.  Global eQTL Mapping Reveals the Complex Genetic Architecture of Transcript-Level Variation in Arabidopsis , 2007, Genetics.

[157]  R. Koebner,et al.  Allosyndetic recombination between a chromosome of Aegilops umbellulata and wheat chromosomes , 1987, Heredity.

[158]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[159]  Jingyuan Fu,et al.  System-wide molecular evidence for phenotypic buffering in Arabidopsis , 2009, Nature Genetics.

[160]  Jingyuan Fu,et al.  Integrative analyses of genetic variation in enzyme activities of primary carbohydrate metabolism reveal distinct modes of regulation in Arabidopsis thaliana , 2008, Genome Biology.

[161]  G. Churchill,et al.  Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F2 Crosses , 2006, Genetics.

[162]  J. Prioul,et al.  Genetic dissection of the relationship between carbon metabolism and early growth in maize, with emphasis on key-enzyme loci , 1995, Molecular Breeding.

[163]  S. Tanksley,et al.  Seed banks and molecular maps: unlocking genetic potential from the wild. , 1997, Science.

[164]  Evandro Novaes,et al.  High-throughput gene and SNP discovery in Eucalyptus grandis, an uncharacterized genome , 2008, BMC Genomics.

[165]  R. Varshney,et al.  Genomics-assisted breeding for crop improvement. , 2005, Trends in plant science.

[166]  Jingyuan Fu,et al.  The genetics of plant metabolism , 2006, Nature Genetics.

[167]  O. Fiehn.  Metabolomics – the link between genotypes and phenotypes , 2004, Plant Molecular Biology.

[168]  M. Koornneef,et al.  The genetics of phytate and phosphate accumulation in seeds and leaves of Arabidopsis thaliana, using natural variation , 2003, Theoretical and Applied Genetics.

[169]  S. Tanksley,et al.  Development of a set of near isogenic and backcross recombinant inbred lines containing most of the Lycopersicon hirsutum genome in a L. esculentum genetic background: a tool for gene mapping and gene discovery. , 2000, Genome.

[170]  J. Slate,et al.  INVITED REVIEW: Quantitative trait locus mapping in natural populations: progress, caveats and future directions , 2004, Molecular ecology.

[171]  Oliver Fiehn,et al.  Applications of metabolomics in agriculture. , 2006, Journal of agricultural and food chemistry.

[172]  P. Christou,et al.  ‘Green revolution’ genes encode mutant gibberellin response modulators , 1999, Nature.

[173]  Ilan Paran,et al.  Quantitative traits in plants: beyond the QTL. , 2003, Trends in genetics : TIG.

[174]  J. Beynon,et al.  STAIRS: a new genetic resource for functional genomic studies of Arabidopsis. , 2002, The Plant journal : for cell and molecular biology.

[175]  J. Dvorak,et al.  Single nucleotide polymorphism genotyping in polyploid wheat with the Illumina GoldenGate assay , 2009, Theoretical and Applied Genetics.

[176]  Susan McCouch,et al.  Diversifying Selection in Plant Breeding , 2004, PLoS biology.

[177]  M. Koornneef,et al.  Pleiotropic effects of the Arabidopsis cryptochrome 2 allelic variation underlie fruit trait-related QTL. , 2004, Plant biology.

[178]  O. Loudet,et al.  Divergent Evolution of Duplicate Genes Leads to Genetic Incompatibilities Within A. thaliana , 2009, Science.

[179]  A. Melchinger,et al.  Comparison of mixed-model approaches for association mapping in rapeseed, potato, sugar beet, maize, and Arabidopsis , 2009, BMC Genomics.

[180]  W. W. Adams,et al.  Antioxidants in Photosynthesis and Human Nutrition , 2002, Science.

[181]  Detlef Weigel,et al.  Genome-wide patterns of single-feature polymorphism in Arabidopsis thaliana , 2007, Proceedings of the National Academy of Sciences.

[182]  Shirong Zhang,et al.  A phenylalanine in DGAT is a key determinant of oil content and composition in maize , 2008, Nature Genetics.

[183]  Lloyd W Sumner,et al.  Genomics-based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula. , 2005, The Plant journal : for cell and molecular biology.

[184]  Thomas Altmann,et al.  SNP identification in crop plants. , 2009, Current opinion in plant biology.

[185]  J. Nap,et al.  Genetical genomics : the added value from segregation , 2001 .

[186]  Z. Fei,et al.  Identification of Solanum habrochaites loci that quantitatively influence tomato fruit ripening-associated ethylene emissions , 2009, Theoretical and Applied Genetics.

[187]  J. A. Jarillo,et al.  Regulation of flowering time by FVE, a retinoblastoma-associated protein , 2004, Nature Genetics.

[188]  L. Willmitzer,et al.  13C isotope-labeled metabolomes allowing for improved compound annotation and relative quantification in liquid chromatography-mass spectrometry-based metabolomic research. , 2009, Analytical chemistry.

[189]  D. Zamir,et al.  A genetic map of candidate genes and QTLs involved in tomato fruit size and composition. , 2004, Journal of experimental botany.

[190]  M. Kearsey,et al.  More QTL for flowering time revealed by substitution lines in Brassica oleracea , 1999, Heredity.

[191]  Mark G. M. Aarts,et al.  What Has Natural Variation Taught Us about Plant Development, Physiology, and Adaptation? , 2009, The Plant Cell Online.

[192]  D. Zamir.  Plant breeders go back to nature , 2008, Nature Genetics.

[193]  M. Blair,et al.  QTL analysis of yield traits in an advanced backcross population derived from a cultivated Andean × wild common bean (Phaseolus vulgaris L.) cross , 2006, Theoretical and Applied Genetics.

[194]  Rod Jones,et al.  Class targeted metabolomics: ESI ion trap screening methods for glucosinolates based on MSn fragmentation. , 2008, Phytochemistry.

[195]  D. Herms,et al.  The Dilemma of Plants: To Grow or Defend , 1992, The Quarterly Review of Biology.

[196]  M. Ganal,et al.  Advanced backcross QTL analysis for the identification of quantitative trait loci alleles from wild relatives of wheat (Triticum aestivum L.) , 2003, Theoretical and Applied Genetics.

[197]  D. Zamir,et al.  Unused Natural Variation Can Lift Yield Barriers in Plant Breeding , 2004, PLoS biology.

[198]  G. Coupland,et al.  Control of flowering time: interacting pathways as a basis for diversity. , 2002, The Plant cell.

[199]  F. Carrari,et al.  Zooming In on a Quantitative Trait for Tomato Yield Using Interspecific Introgressions , 2004, Science.

[200]  Richard M. Clark,et al.  Common Sequence Polymorphisms Shaping Genetic Diversity in Arabidopsis thaliana , 2007, Science.

[201]  R. Chetelat,et al.  Transmission and recombination of homeologous Solanum sitiens chromosomes in tomato , 2003, Theoretical and Applied Genetics.

[202]  Martin Kuiper,et al.  Genetic Analysis of Variation in Gene Expression in Arabidopsis thaliana , 2005, Genetics.

[203]  Robert D. Hall,et al.  Metabolomics of a model fruit: tomato , 2011 .

[204]  Faye M. Rosin,et al.  RNA Interference Silencing of Chalcone Synthase, the First Step in the Flavonoid Biosynthesis Pathway, Leads to Parthenocarpic Tomato Fruits[C] , 2007, Plant Physiology.

[205]  N. Warthmann,et al.  Autoimmune Response as a Mechanism for a Dobzhansky-Muller-Type Incompatibility Syndrome in Plants , 2007, PLoS biology.

[206]  Joachim Selbig,et al.  Identification of metabolic and biomass QTL in Arabidopsis thaliana in a parallel analysis of RIL and IL populations , 2007, The Plant journal : for cell and molecular biology.

[207]  Hongyan Liu,et al.  PlantQTL-GE: a database system for identifying candidate genes in rice and Arabidopsis by gene expression and QTL information , 2006, Nucleic Acids Res..

[208]  Alan M. Jones,et al.  The Impact of Arabidopsis on Human Health: Diversifying Our Portfolio , 2008, Cell.

[209]  Howard V. Davies,et al.  Comparison of Tuber Proteomes of Potato Varieties, Landraces, and Genetically Modified Lines1 , 2005, Plant Physiology.

[210]  Madan K. Bhattacharyya,et al.  The wrinkled-seed character of pea described by Mendel is caused by a transposon-like insertion in a gene encoding starch-branching enzyme , 1990, Cell.

[211]  Kazuki Saito,et al.  Application of a metabolomic method combining one-dimensional and two-dimensional gas chromatography-time-of-flight/mass spectrometry to metabolic phenotyping of natural variants in rice. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[212]  Yury Tikunov,et al.  A Novel Approach for Nontargeted Data Analysis for Metabolomics. Large-Scale Profiling of Tomato Fruit Volatiles1[w] , 2005, Plant Physiology.

[213]  S. Smeekens,et al.  The Arabidopsis GSQ5/DOG1 Cvi allele is induced by the ABA-mediated sugar signalling pathway, and enhances sugar sensitivity by stimulating ABI4 expression. , 2008, The Plant journal : for cell and molecular biology.

[214]  T. Rocheford,et al.  Maize selection passes the century mark: a unique resource for 21st century genomics. , 2004, Trends in plant science.

[215]  Charles L. Guy,et al.  Exploring the Temperature-Stress Metabolome of Arabidopsis1[w] , 2004, Plant Physiology.

[216]  E. Lander,et al.  Analysing complex genetic traits with chromosome substitution strains , 2000, Nature Genetics.

[217]  S. Tanksley,et al.  Regulatory change in YABBY-like transcription factor led to evolution of extreme fruit size during tomato domestication , 2008, Nature Genetics.

[218]  S. Tanksley,et al.  Comparative fine mapping of fruit quality QTLs on chromosome 4 introgressions derived from two wild tomato species , 2004, Euphytica.

[219]  Rita H. Mumm,et al.  Molecular Plant Breeding as the Foundation for 21st Century Crop Improvement1 , 2008, Plant Physiology.

[220]  M. Todesco,et al.  A Genetic Defect Caused by a Triplet Repeat Expansion in Arabidopsis thaliana , 2009, Science.

[221]  Pilar Cubas,et al.  An epigenetic mutation responsible for natural variation in ̄ oral symmetry , 2022 .

[222]  S. Salvi,et al.  To clone or not to clone plant QTLs: present and future challenges. , 2005, Trends in plant science.

[223]  Tadashi Eguchi,et al.  Metabolite profiling of plant carotenoids using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry. , 2007, The Plant journal : for cell and molecular biology.

[224]  T. Mitchell-Olds,et al.  The molecular basis of quantitative genetic variation in central and secondary metabolism in Arabidopsis. , 1998, Genetics.

[225]  A. Fernie.  The future of metabolic phytochemistry: larger numbers of metabolites, higher resolution, greater understanding. , 2007, Phytochemistry.

[226]  M Koornneef,et al.  Naturally occurring variation in Arabidopsis: an underexploited resource for plant genetics. , 2000, Trends in plant science.

[227]  Michael A. Costa,et al.  An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof. , 2003, Phytochemistry.

[228]  M. Morgante,et al.  Contrasting Effects of Selection on Sequence Diversity and Linkage Disequilibrium at Two Phytoene Synthase Loci Online version contains Web-only data. Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.012526. , 2003, The Plant Cell Online.

[229]  J. Keurentjes,et al.  Quantitative genetics in the age of omics. , 2008, Current opinion in plant biology.

[230]  M. Koornneef,et al.  Analysis of natural allelic variation at seed dormancy loci of Arabidopsis thaliana. , 2003, Genetics.

[231]  C. E. Bessey.  Crop Improvement by Utilizing Wild Species , 1906 .

[232]  F. V. van Eeuwijk,et al.  Association mapping of leaf traits, flowering time, and phytate content in Brassica rapa. , 2007, Genome.

[233]  O. Loudet,et al.  Natural Variation for Carbohydrate Content in Arabidopsis. Interaction with Complex Traits Dissected by Quantitative Genetics1 , 2006, Plant Physiology.

[234]  E. Fridman,et al.  A recombination hotspot delimits a wild-species quantitative trait locus for tomato sugar content to 484 bp within an invertase gene. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[235]  A. Trubuil,et al.  Quantitative trait loci controlling root growth and architecture in Arabidopsis thaliana confirmed by heterogeneous inbred family , 2005, Theoretical and Applied Genetics.

[236]  K. Broman,et al.  Review of statistical methods for QTL mapping in experimental crosses. , 2001, Lab animal.

[237]  R. Hall,et al.  Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors , 2008, Nature Biotechnology.

[238]  Henning Redestig,et al.  Data Integration, Metabolic Networks and Systems Biology , 2011 .

[239]  Justin O. Borevitz,et al.  Global Analysis of Genetic, Epigenetic and Transcriptional Polymorphisms in Arabidopsis thaliana Using Whole Genome Tiling Arrays , 2008, PLoS genetics.

[240]  H. Piepho,et al.  Association mapping in multiple segregating populations of sugar beet (Beta vulgaris L.) , 2008, Theoretical and Applied Genetics.

[241]  A. Fernie,et al.  Metabolomics-assisted breeding: a viable option for crop improvement? , 2009, Trends in genetics : TIG.

[242]  G. Bernier,et al.  The role of carbohydrates in the induction of flowering in Arabidopsis thaliana: comparison between the wild type and a starchless mutant , 1998, Planta.

[243]  R. Amasino,et al.  Natural allelic variation identifies new genes in the Arabidopsis circadian system. , 1999, The Plant journal : for cell and molecular biology.

[244]  D. Bartel,et al.  MicroRNAS and their regulatory roles in plants. , 2006, Annual review of plant biology.

[245]  M. Wink.  Plant breeding: importance of plant secondary metabolites for protection against pathogens and herbivores , 2004, Theoretical and Applied Genetics.