Home LiteratureArticle Details
PMID: 23144785 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

PICARA, an analytical pipeline providing probabilistic inference about a priori candidates genes underlying genome-wide association QTL in plants.

PloS one ·Vol. 7 ·No. 11 ·2012-00-00 ·Pages e46596

Chen C, DeClerck G, Tian F, Spooner W, McCouch S, Buckler E

Abstract

PICARA is an analytical pipeline designed to systematically summarize observed SNP/trait associations identified by genome wide association studies (GWAS) and to identify candidate genes involved in the regulation of complex trait variation. The pipeline provides probabilistic inference about a priori candidate genes using integrated information derived from genome-wide association signals, gene homology, and curated gene sets embedded in pathway descriptions. In this paper, we demonstrate the performance of PICARA using data for flowering time variation in maize - a key trait for geographical and seasonal adaption of plants. Among 406 curated flowering time-related genes from Arabidopsis, we identify 61 orthologs in maize that are significantly enriched for GWAS SNP signals, including key regulators such as FT (Flowering Locus T) and GI (GIGANTEA), and genes centered in the Arabidopsis circadian pathway, including TOC1 (Timing of CAB Expression 1) and LHY (Late Elongated Hypocotyl). In addition, we discover a regulatory feature that is characteristic of these a priori flowering time candidates in maize. This new probabilistic analytical pipeline helps researchers infer the functional significance of candidate genes associated with complex traits and helps guide future experiments by providing statistical support for gene candidates based on the integration of heterogeneous biological information.

MeSH Terms
Arabidopsis/genetics Arabidopsis Proteins/genetics Gene Expression Regulation, Plant Genes, Plant Models, Genetic Polymorphism, Single Nucleotide Probability Quantitative Trait Loci
Chemicals
Arabidopsis Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chen Charles
Department of Plant Breeding and Genetics, Cornell University, Ithaca, New York, United States of America. [email protected]
DeClerck Genevieve
Tian Feng
Spooner William
McCouch Susan
Buckler Edward
References (66)
66 references, click to expand
  1. Genome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa.
    Nat Commun. 2011 Sep 13;2:467 PMID: 21915109
  2. Genome-wide temporal-spatial gene expression profiling of drought responsiveness in rice.
    BMC Genomics. 2011 Mar 16;12:149 PMID: 21406116
  3. Mutation discovery for crop improvement.
    J Exp Bot. 2009;60(10):2817-25 PMID: 19516074
  4. Positional cloning of rice semidwarfing gene, sd-1: rice "green revolution gene" encodes a mutant enzyme involved in gibberellin synthesis.
    DNA Res. 2002 Feb 28;9(1):11-7 PMID: 11939564
  5. Poorly known relatives of Arabidopsis thaliana.
    Trends Plant Sci. 2006 Sep;11(9):449-59 PMID: 16893672
  6. Structure of linkage disequilibrium and phenotypic associations in the maize genome.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11479-84 PMID: 11562485
  7. Genomic colinearity as a tool for plant gene isolation.
    Methods Mol Biol. 2003;236:109-22 PMID: 14501061
  8. THE POPULATION GENETICS OF ADAPTATION: THE DISTRIBUTION OF FACTORS FIXED DURING ADAPTIVE EVOLUTION.
    Evolution. 1998 Aug;52(4):935-949 PMID: 28565213
  9. Evolutionary constraints on structural similarity in orthologs and paralogs.
    Protein Sci. 2009 Jun;18(6):1306-15 PMID: 19472362
  10. Subcellular localization and functional domain studies of DEFECTIVE KERNEL1 in maize and Arabidopsis suggest a model for aleurone cell fate specification involving CRINKLY4 and SUPERNUMERARY ALEURONE LAYER1.
    Plant Cell. 2007 Oct;19(10):3127-45 PMID: 17933905
  11. Gramene database in 2010: updates and extensions.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D1085-94 PMID: 21076153
  12. Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines.
    Nature. 2010 Jun 3;465(7298):627-31 PMID: 20336072
  13. PLEXdb: gene expression resources for plants and plant pathogens.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D1194-201 PMID: 22084198
  14. High gene density is conserved at syntenic loci of small and large grass genomes.
    Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8265-70 PMID: 10393983
  15. Structure of linkage disequilibrium in plants.
    Annu Rev Plant Biol. 2003;54:357-74 PMID: 14502995
  16. The B73 maize genome: complexity, diversity, and dynamics.
    Science. 2009 Nov 20;326(5956):1112-5 PMID: 19965430
  17. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
    Nat Protoc. 2009;4(1):44-57 PMID: 19131956
  18. A first-generation haplotype map of maize.
    Science. 2009 Nov 20;326(5956):1115-7 PMID: 19965431
  19. Orthologs, paralogs, and evolutionary genomics.
    Annu Rev Genet. 2005;39:309-38 PMID: 16285863
  20. SNP-based pathway enrichment analysis for genome-wide association studies.
    BMC Bioinformatics. 2011 Apr 15;12:99 PMID: 21496265
  21. Forward genetics and map-based cloning approaches.
    Trends Plant Sci. 2003 Oct;8(10):484-91 PMID: 14557045
  22. Convergent domestication of cereal crops by independent mutations at corresponding genetic Loci.
    Science. 1995 Sep 22;269(5231):1714-8 PMID: 17821643
  23. Association mapping of local climate-sensitive quantitative trait loci in Arabidopsis thaliana.
    Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21199-204 PMID: 21078970
  24. Genetic characterization and linkage disequilibrium estimation of a global maize collection using SNP markers.
    PLoS One. 2009 Dec 24;4(12):e8451 PMID: 20041112
  25. Disease-associated loci are significantly over-represented among genes bound by transcription factor 7-like 2 (TCF7L2) in vivo.
    Diabetologia. 2010 Nov;53(11):2340-6 PMID: 20640398
  26. Arabidopsis-rice: will colinearity allow gene prediction across the eudicot-monocot divide?
    Genome Res. 1999 Sep;9(9):825-9 PMID: 10508840
  27. Genetic mapping in human disease.
    Science. 2008 Nov 7;322(5903):881-8 PMID: 18988837
  28. The defective seed5 (des5) mutant: effects on barley seed development and HvDek1, HvCr4, and HvSal1 gene regulation.
    J Exp Bot. 2008;59(13):3753-65 PMID: 18791195
  29. Transcriptional profiling reveals novel interactions between wounding, pathogen, abiotic stress, and hormonal responses in Arabidopsis.
    Plant Physiol. 2002 Jun;129(2):661-77 PMID: 12068110
  30. Microcolinearity in sh2-homologous regions of the maize, rice, and sorghum genomes.
    Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3431-5 PMID: 9096411
  31. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
    Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 PMID: 19474294
  32. Genome-wide association study of leaf architecture in the maize nested association mapping population.
    Nat Genet. 2011 Feb;43(2):159-62 PMID: 21217756
  33. EnsemblCompara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates.
    Genome Res. 2009 Feb;19(2):327-35 PMID: 19029536
  34. TASSEL: software for association mapping of complex traits in diverse samples.
    Bioinformatics. 2007 Oct 1;23(19):2633-5 PMID: 17586829
  35. Genome-wide association studies of 14 agronomic traits in rice landraces.
    Nat Genet. 2010 Nov;42(11):961-7 PMID: 20972439
  36. Conserved noncoding genomic sequences associated with a flowering-time quantitative trait locus in maize.
    Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11376-81 PMID: 17595297
  37. CMap 1.01: a comparative mapping application for the Internet.
    Bioinformatics. 2009 Nov 15;25(22):3040-2 PMID: 19648141
  38. ConsensusPathDB--a database for integrating human functional interaction networks.
    Nucleic Acids Res. 2009 Jan;37(Database issue):D623-8 PMID: 18940869
  39. The biological basis of epistasis between quantitative trait loci for flavone and 3-deoxyanthocyanin synthesis in maize (Zea mays L.).
    Genome. 2001 Aug;44(4):667-76 PMID: 11550903
  40. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  41. Functional diversification of paralogous transcription factors via divergence in DNA binding site motif and in expression.
    PLoS One. 2008 Jun 04;3(6):e2345 PMID: 18523562
  42. A haplotype map of the human genome.
    Nature. 2005 Oct 27;437(7063):1299-320 PMID: 16255080
  43. Natural and artificial mutants as valuable resources for functional genomics and molecular breeding.
    Int J Biol Sci. 2010 Apr 28;6(3):228-51 PMID: 20440406
  44. Positional cloning of the wheat vernalization gene VRN1.
    Proc Natl Acad Sci U S A. 2003 May 13;100(10):6263-8 PMID: 12730378
  45. Phytochromes promote seedling light responses by inhibiting four negatively-acting phytochrome-interacting factors.
    Proc Natl Acad Sci U S A. 2009 May 5;106(18):7660-5 PMID: 19380720
  46. Genetic design and statistical power of nested association mapping in maize.
    Genetics. 2008 Jan;178(1):539-51 PMID: 18202393
  47. Functional characterization of phytochrome interacting factor 3 in phytochrome-mediated light signal transduction.
    Plant Cell. 2003 Oct;15(10):2399-407 PMID: 14508006
  48. The genetic architecture of maize flowering time.
    Science. 2009 Aug 7;325(5941):714-8 PMID: 19661422
  49. Genetic architecture of aluminum tolerance in rice (Oryza sativa) determined through genome-wide association analysis and QTL mapping.
    PLoS Genet. 2011 Aug;7(8):e1002221 PMID: 21829395
  50. Genome-wide association study for colorectal cancer identifies risk polymorphisms in German familial cases and implicates MAPK signalling pathways in disease susceptibility.
    Carcinogenesis. 2010 Sep;31(9):1612-9 PMID: 20610541
  51. The Plant Ontology Database: a community resource for plant structure and developmental stages controlled vocabulary and annotations.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D449-54 PMID: 18194960
  52. Extensive long-range and nonsyntenic linkage disequilibrium in livestock populations: deconstruction of a conundrum.
    Genetics. 2009 Feb;181(2):691-9 PMID: 19087960
  53. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
  54. A second generation human haplotype map of over 3.1 million SNPs.
    Nature. 2007 Oct 18;449(7164):851-61 PMID: 17943122
  55. Emerging use of gene expression microarrays in plant physiology.
    Comp Funct Genomics. 2003;4(2):216-24 PMID: 18629133
  56. The genetics of maize evolution.
    Annu Rev Genet. 2004;38:37-59 PMID: 15568971
  57. TILLING in grass species.
    Plant Physiol. 2009 Jan;149(1):158-64 PMID: 19126709
  58. The CONSTANS gene of Arabidopsis promotes flowering and encodes a protein showing similarities to zinc finger transcription factors.
    Cell. 1995 Mar 24;80(6):847-57 PMID: 7697715
  59. Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder.
    Am J Hum Genet. 2009 Jul;85(1):13-24 PMID: 19539887
  60. Physical and genetic structure of the maize genome reflects its complex evolutionary history.
    PLoS Genet. 2007 Jul;3(7):e123 PMID: 17658954
  61. Flowering time control and applications in plant breeding.
    Trends Plant Sci. 2009 Oct;14(10):563-73 PMID: 19716745
  62. DNA microarrays for functional plant genomics.
    Plant Mol Biol. 2002 Jan;48(1-2):99-118 PMID: 11860216
  63. The Arabidopsis Paf1c complex component CDC73 participates in the modification of FLOWERING LOCUS C chromatin.
    Plant Physiol. 2010 Jul;153(3):1074-84 PMID: 20463090
  64. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization.
    Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11 PMID: 19465376
  65. GSEA-SNP: applying gene set enrichment analysis to SNP data from genome-wide association studies.
    Bioinformatics. 2008 Dec 1;24(23):2784-5 PMID: 18854360
  66. agriGO: a GO analysis toolkit for the agricultural community.
    Nucleic Acids Res. 2010 Jul;38(Web Server issue):W64-70 PMID: 20435677
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
Published
2012-00-00
Epub
2012-00-07
Pages
e46596
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3492367
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]