Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork

BackgroundA typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community.DescriptionUsing a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork http://www.genenetwork.org. GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits). Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them.ConclusionBy integrating barley genotypic, phenotypic and mRNA abundance data sets directly within GeneNetwork's analytical environment we provide simple web access to the data for the research community. In this environment, a combination of correlation analysis and linkage mapping provides the potential to identify and substantiate gene targets for saturation mapping and positional cloning. By integrating datasets from an unsequenced crop plant (barley) in a database that has been designed for an animal model species (mouse) with a well established genome sequence, we prove the importance of the concept and practice of modular development and interoperability of software engineering for biological data sets.

[1]  V. Ambros,et al.  Control of developmental timing in Caenorhabditis elegans. , 2000, Current opinion in genetics & development.

[2]  J. Josse,et al.  Quantitative trait loci underlying gene product variation: a novel perspective for analyzing regulation of genome expression. , 1994, Genetics.

[3]  J. Castle,et al.  An integrative genomics approach to infer causal associations between gene expression and disease , 2005, Nature Genetics.

[4]  P. Hayes,et al.  Comprehensive genetic analyses reveal differential expression of spot blotch resistance in four populations of barley , 2005, Theoretical and Applied Genetics.

[5]  Ute Baumann,et al.  An atlas of gene expression from seed to seed through barley development , 2006, Functional & Integrative Genomics.

[6]  D. Kudrna,et al.  A molecular, isozyme and morphological map of the barley (Hordeum vulgare) genome , 1993, Theoretical and Applied Genetics.

[7]  R. Mauricio Mapping quantitative trait loci in plants: uses and caveats for evolutionary biology , 2001, Nature Reviews Genetics.

[8]  Travis W. Banks,et al.  Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci. , 2007, Plant biotechnology journal.

[9]  Rongling Wu,et al.  Statistical Genetics of Quantitative Traits: Linkage, Maps and QTL , 2007 .

[10]  Robert W. Williams,et al.  WebQTL - Web-based complex trait analysis , 2003, Neuroinformatics.

[11]  Lu Lu,et al.  WebQTL: rapid exploratory analysis of gene expression and genetic networks for brain and behavior , 2004, Nature Neuroscience.

[12]  S. Knapp,et al.  Quantitative trait locus effects and environmental interaction in a sample of North American barley germ plasm , 1993, Theoretical and Applied Genetics.

[13]  P M Visscher,et al.  Confidence intervals in QTL mapping by bootstrapping. , 1996, Genetics.

[14]  J. Bennewitz,et al.  Improved confidence intervals in quantitative trait loci mapping by permutation bootstrapping. , 2002, Genetics.

[15]  R. Wu,et al.  Functional mapping — how to map and study the genetic architecture of dynamic complex traits , 2006, Nature Reviews Genetics.

[16]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[17]  Matthew A. Hibbs,et al.  Discovery of biological networks from diverse functional genomic data , 2005, Genome Biology.

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

[19]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[20]  Jian Gong,et al.  BarleyBase—an expression profiling database for plant genomics , 2004, Nucleic Acids Res..

[21]  Tao Jiang,et al.  Efficient selection of unique and popular oligos for large EST databases , 2004, Bioinform..

[22]  S. Wanamaker,et al.  Genome-wide SNP discovery and linkage analysis in barley based on genes responsive to abiotic stress , 2005, Molecular Genetics and Genomics.

[23]  D. Nettleton,et al.  Interaction-Dependent Gene Expression in Mla-Specified Response to Barley Powdery Mildeww⃞ , 2004, The Plant Cell Online.

[24]  Rongling Wu,et al.  A statistical model for high‐resolution mapping of quantitative trait loci determining HIV dynamics , 2004, Statistics in medicine.

[25]  Jintao Wang,et al.  Genetic correlates of gene expression in recombinant inbred strains , 2007, Neuroinformatics.

[26]  Rajeev K. Varshney,et al.  Recent history of artificial outcrossing facilitates whole-genome association mapping in elite inbred crop varieties , 2006, Proceedings of the National Academy of Sciences.

[27]  R. Sederoff,et al.  Genetic Architecture of Transcript-Level Variation in Differentiating Xylem of a Eucalyptus Hybrid , 2005, Genetics.

[28]  Rongling Wu,et al.  Functional Mapping of Quantitative Trait Loci That Interact With the hg Mutation to Regulate Growth Trajectories in Mice , 2005, Genetics.

[29]  R. Stoughton,et al.  Genetics of gene expression surveyed in maize, mouse and man , 2003, Nature.

[30]  T. Friesen,et al.  Identification and chromosomal location of major genes for resistance to Pyrenophora teres in a doubled-haploid barley population. , 2006, Genome.

[31]  Robert W. Williams,et al.  Exploiting regulatory variation to identify genes underlying quantitative resistance to the wheat stem rust pathogen Puccinia graminis f. sp. tritici in barley , 2008, Theoretical and Applied Genetics.

[32]  T. Gingeras,et al.  Microarrays and genetic epidemiology: A multipurpose tool for a multifaceted field , 2002, Genetic epidemiology.

[33]  P. Hayes,et al.  Disequilibrium and association in barley: Thinking outside the glass , 2006, Proceedings of the National Academy of Sciences.

[34]  L. Kruglyak,et al.  Genetic Dissection of Transcriptional Regulation in Budding Yeast , 2002, Science.

[35]  A. Perelson,et al.  HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time , 1996, Science.

[36]  D. Nettleton,et al.  Stage-specific suppression of basal defense discriminates barley plants containing fast- and delayed-acting Mla powdery mildew resistance alleles. , 2006, Molecular plant-microbe interactions : MPMI.

[37]  R. Doerge Multifactorial genetics: Mapping and analysis of quantitative trait loci in experimental populations , 2002, Nature Reviews Genetics.

[38]  Kothandaraman Narasimhan,et al.  Metabolomics and its role in understanding cellular responses in plants , 2005, Plant Cell Reports.

[39]  Dan Nettleton,et al.  Genetic Regulation of Gene Expression During Shoot Development in Arabidopsis , 2006, Genetics.

[40]  T. Mackay,et al.  Quantitative genetic analyses of complex behaviours in Drosophila , 2004, Nature Reviews Genetics.

[41]  R. Varshney,et al.  A high-density consensus map of barley to compare the distribution of QTLs for partial resistance to Puccinia hordei and of defence gene homologues , 2007, Theoretical and Applied Genetics.

[42]  Rongling Wu,et al.  Comprar Statistical Genetics of Quantitative Traits · Linkage, Maps and QTL | Casella, George | 9780387203348 | Springer , 2007 .

[43]  P. Nilsson,et al.  The genetics and genomics of the drought response in Populus. , 2006, The Plant journal : for cell and molecular biology.

[44]  Kenneth F. Manly,et al.  Overview of QTL mapping software and introduction to Map Manager QT , 1999, Mammalian Genome.

[45]  Timothy J Donohue,et al.  Policy proposal for publication of papers with data sets from genome-wide studies. , 2004, Microbiology.

[46]  Paul M. Magwene,et al.  Estimating genomic coexpression networks using first-order conditional independence , 2004, Genome Biology.

[47]  R. Sederoff,et al.  Coordinated Genetic Regulation of Growth and Lignin Revealed by Quantitative Trait Locus Analysis of cDNA Microarray Data in an Interspecific Backcross of Eucalyptus1 , 2004, Plant Physiology.

[48]  A. Kleinhofs,et al.  Parallel expression profiling of barley–stem rust interactions , 2008, Functional & Integrative Genomics.

[49]  G. Casella,et al.  Functional mapping of quantitative trait loci underlying the character process: a theoretical framework. , 2002, Genetics.

[50]  R. Waugh,et al.  SFP Genotyping From Affymetrix Arrays Is Robust But Largely Detects Cis-acting Expression Regulators , 2007, Genetics.

[51]  Milena Ouzunova,et al.  Identification of candidate genes associated with cell wall digestibility and eQTL (expression quantitative trait loci) analysis in a Flint × Flint maize recombinant inbred line population , 2007, BMC Genomics.

[52]  Wei Zhao,et al.  Gramene: a resource for comparative grass genomics , 2002, Nucleic Acids Res..

[53]  Robbie Waugh,et al.  Gene expression quantitative trait locus analysis of 16 000 barley genes reveals a complex pattern of genome-wide transcriptional regulation. , 2008, The Plant journal : for cell and molecular biology.

[54]  Tianwei Yu,et al.  Study of coordinative gene expression at the biological process level , 2005, Bioinform..

[55]  A. Rougvie Control of developmental timing in animals , 2001, Nature Reviews Genetics.

[56]  Gerard R. Lazo,et al.  GrainGenes, the genome database for small-grain crops , 2003, Nucleic Acids Res..