Detection of Epistasis for Flowering Time Using Bayesian Multilocus Estimation in a Barley MAGIC Population

Flowering time is a well-known complex trait in crops and is influenced by many interacting genes. In this study, Mathew et al. identify two-way and.... Gene-by-gene interactions, also known as epistasis, regulate many complex traits in different species. With the availability of low-cost genotyping it is now possible to study epistasis on a genome-wide scale. However, identifying genome-wide epistasis is a high-dimensional multiple regression problem and needs the application of dimensionality reduction techniques. Flowering Time (FT) in crops is a complex trait that is known to be influenced by many interacting genes and pathways in various crops. In this study, we successfully apply Sure Independence Screening (SIS) for dimensionality reduction to identify two-way and three-way epistasis for the FT trait in a Multiparent Advanced Generation Inter-Cross (MAGIC) barley population using the Bayesian multilocus model. The MAGIC barley population was generated from intercrossing among eight parental lines and thus, offered greater genetic diversity to detect higher-order epistatic interactions. Our results suggest that SIS is an efficient dimensionality reduction approach to detect high-order interactions in a Bayesian multilocus model. We also observe that many of our findings (genomic regions with main or higher-order epistatic effects) overlap with known candidate genes that have been already reported in barley and closely related species for the FT trait.

[1]  Steven J. M. Jones,et al.  Circos: an information aesthetic for comparative genomics. , 2009, Genome research.

[2]  M. Sillanpää,et al.  Advanced backcross-QTL analysis in spring barley (H. vulgare ssp. spontaneum) comparing a REML versus a Bayesian model in multi-environmental field trials , 2009, Theoretical and Applied Genetics.

[3]  Shizhong Xu Estimating polygenic effects using markers of the entire genome. , 2003, Genetics.

[4]  J. Gray,et al.  Light-Induced Stomatal Opening Is Affected by the Guard Cell Protein Kinase APK1b , 2014, PloS one.

[5]  W. Powell,et al.  From mutations to MAGIC: resources for gene discovery, validation and delivery in crop plants. , 2008, Current opinion in plant biology.

[6]  W. G. Hill,et al.  Influence of Gene Interaction on Complex Trait Variation with Multilocus Models , 2014, Genetics.

[7]  David J. C. MacKay,et al.  BAYESIAN NON-LINEAR MODELING FOR THE PREDICTION COMPETITION , 1996 .

[8]  R. Mott,et al.  A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana , 2009, PLoS genetics.

[9]  S. van Nocker,et al.  The WD-repeat protein superfamily in Arabidopsis: conservation and divergence in structure and function , 2003, BMC Genomics.

[10]  Chris S. Haley,et al.  Detecting epistasis in human complex traits , 2014, Nature Reviews Genetics.

[11]  Jason H Moore,et al.  Computational analysis of gene-gene interactions using multifactor dimensionality reduction , 2004, Expert review of molecular diagnostics.

[12]  D. Wagner,et al.  Genomic identification of direct target genes of LEAFY. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Yingfang Zhu,et al.  ABA receptor PYL9 promotes drought resistance and leaf senescence , 2016, Proceedings of the National Academy of Sciences.

[14]  Donald Geman,et al.  Stochastic Relaxation, Gibbs Distributions, and the Bayesian Restoration of Images , 1984, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[15]  Geoffrey E. Hinton,et al.  Bayesian Learning for Neural Networks , 1995 .

[16]  Shizhong Xu,et al.  A Random-Model Approach to QTL Mapping in Multiparent Advanced Generation Intercross (MAGIC) Populations , 2015, Genetics.

[17]  M. Sillanpää,et al.  Bayesian mapping of genotype × expression interactions in quantitative and qualitative traits , 2006, Heredity.

[18]  George Eastman House,et al.  Sparse Bayesian Learning and the Relevance Vector Machine , 2001 .

[19]  A. Graner,et al.  Induced mutations in circadian clock regulator Mat-a facilitated short-season adaptation and range extension in cultivated barley , 2012, Proceedings of the National Academy of Sciences.

[20]  S. Komatsu,et al.  Expression Analyses of β-tubulin Isotype Genes in Rice , 2003 .

[21]  K. Niyogi,et al.  Mutations in Arabidopsis YCF20-like genes affect thermal dissipation of excess absorbed light energy , 2010, Planta.

[22]  K. Krystkowiak,et al.  Effects of the semi-dwarfing sdw1/denso gene in barley , 2013, Journal of Applied Genetics.

[23]  Andrew W George,et al.  A multiparent advanced generation inter-cross population for genetic analysis in wheat. , 2012, Plant biotechnology journal.

[24]  A. Leyland,et al.  Empirical Bayes methods for disease mapping , 2005, Statistical methods in medical research.

[25]  Mikko J Sillanpää,et al.  Detecting Interactions in Association Studies by Using Simple Allele Recoding , 2008, Human Heredity.

[26]  K. Lindsey,et al.  Importance of plant sterols in pattern formation and hormone signalling. , 2003, Trends in plant science.

[27]  Yanming Zhu,et al.  GsSRK, a G-type lectin S-receptor-like serine/threonine protein kinase, is a positive regulator of plant tolerance to salt stress. , 2013, Journal of plant physiology.

[28]  J. Reif,et al.  Modelling the genetic architecture of flowering time control in barley through nested association mapping , 2015, BMC Genomics.

[29]  James Cockram,et al.  An Eight-Parent Multiparent Advanced Generation Inter-Cross Population for Winter-Sown Wheat: Creation, Properties, and Validation , 2014, G3: Genes, Genomes, Genetics.

[30]  M. Purugganan,et al.  Epistatic interaction between Arabidopsis FRI and FLC flowering time genes generates a latitudinal cline in a life history trait. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. H. Moore,et al.  Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus , 2004, Diabetologia.

[32]  P. Visscher,et al.  Another Explanation for Apparent Epistasis , 2014 .

[33]  M. Matsuoka,et al.  Loss-of-function mutations of the rice GAMYB gene impair alpha-amylase expression in aleurone and flower development. , 2004, The Plant cell.

[34]  N. Yi,et al.  Bayesian LASSO for Quantitative Trait Loci Mapping , 2008, Genetics.

[35]  Dan He,et al.  Data-driven encoding for quantitative genetic trait prediction , 2015, BMC Bioinformatics.

[36]  Laxmi Parida,et al.  Does encoding matter? A novel view on the quantitative genetic trait prediction problem , 2015, BIBM.

[37]  Mário A. T. Figueiredo Adaptive Sparseness for Supervised Learning , 2003, IEEE Trans. Pattern Anal. Mach. Intell..

[38]  L. Yan,et al.  The wheat and barley vernalization gene VRN3 is an orthologue of FT , 2006, Proceedings of the National Academy of Sciences.

[39]  Taesung Park,et al.  Joint Identification of Multiple Genetic Variants via Elastic‐Net Variable Selection in a Genome‐Wide Association Analysis , 2010, Annals of human genetics.

[40]  P. Hayes,et al.  Molecular and Structural Characterization of Barley Vernalization Genes , 2005, Plant Molecular Biology.

[41]  Benjamin A. Logsdon,et al.  A variational Bayes algorithm for fast and accurate multiple locus genome-wide association analysis , 2010, BMC Bioinformatics.

[42]  T. Nelson,et al.  The Sterol Methyltransferases SMT 1 , SMT 2 , and SMT 3 Influence Arabidopsis Development through Nonbrassinosteroid Products 1 [ W ] [ OA ] , 2010 .

[43]  Shizhong Xu,et al.  An Empirical Bayes Method for Estimating Epistatic Effects of Quantitative Trait Loci , 2007, Biometrics.

[44]  D. Laurie,et al.  The Pseudo-Response Regulator Ppd-H1 Provides Adaptation to Photoperiod in Barley , 2005, Science.

[45]  E. Durand,et al.  Flowering Time in Maize: Linkage and Epistasis at a Major Effect Locus , 2012, Genetics.

[46]  Susan McCouch,et al.  Multi-parent advanced generation inter-cross (MAGIC) populations in rice: progress and potential for genetics research and breeding , 2013, Rice.

[47]  Runze Li,et al.  A FAST ALGORITHM FOR DETECTING GENE-GENE INTERACTIONS IN GENOME-WIDE ASSOCIATION STUDIES. , 2014, The annals of applied statistics.

[48]  M. Sillanpää,et al.  An Efficient Genome-Wide Multilocus Epistasis Search , 2015, Genetics.

[49]  Shane T. Jensen,et al.  LEAFY target genes reveal floral regulatory logic, cis motifs, and a link to biotic stimulus response. , 2011, Developmental cell.

[50]  J. Dubcovsky,et al.  PHYTOCHROME C plays a major role in the acceleration of wheat flowering under long-day photoperiod , 2014, Proceedings of the National Academy of Sciences.

[51]  R. Kalla,et al.  Gibberellin-regulated expression of a myb gene in barley aleurone cells: evidence for Myb transactivation of a high-pI alpha-amylase gene promoter. , 1995, The Plant cell.

[52]  Jianqing Fan,et al.  Sure independence screening for ultrahigh dimensional feature space , 2006, math/0612857.

[53]  W. Peacock,et al.  DNA methylation, vernalization, and the initiation of flowering. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[54]  G. Coupland,et al.  The Evolution of CONSTANS-Like Gene Families in Barley, Rice, and Arabidopsis1 , 2003, Plant Physiology.

[55]  Dabing Zhang,et al.  Jasmonic acid regulates spikelet development in rice , 2014, Nature Communications.

[56]  A. Dewan,et al.  Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases , 2016, G3: Genes, Genomes, Genetics.

[57]  T. Nelson,et al.  The Sterol Methyltransferases SMT1, SMT2, and SMT3 Influence Arabidopsis Development through Nonbrassinosteroid Products1[W][OA] , 2010, Plant Physiology.

[58]  F. Gubler,et al.  The Arabidopsis GAMYB-Like Genes, MYB33 and MYB65, Are MicroRNA-Regulated Genes That Redundantly Facilitate Anther Development , 2005, The Plant Cell Online.

[59]  J. Léon,et al.  Revised Papers , 2003 .

[60]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[61]  Edward J Oakeley,et al.  CONSTITUTIVELY PHOTOMORPHOGENIC1 Is Required for the UV-B Response in Arabidopsis[W] , 2006, The Plant Cell Online.

[62]  B. Mathew,et al.  Multi-parent advanced generation inter-cross in barley: high-resolution quantitative trait locus mapping for flowering time as a proof of concept , 2015, Molecular Breeding.

[63]  Mikko J. Sillanpää,et al.  Bayesian LASSO, Scale Space and Decision Making in Association Genetics , 2015, PloS one.

[64]  M. Schuler,et al.  Cloning of Wound-Induced Cytochrome P450 Monooxygenases Expressed in Pea , 1996, Plant physiology.

[65]  Jian-Kang Zhu,et al.  Arabidopsis mutant deficient in 3 abscisic acid-activated protein kinases reveals critical roles in growth, reproduction, and stress , 2009, Proceedings of the National Academy of Sciences.

[66]  T. Mackay,et al.  The Genetic Architecture of Quantitative Traits Cannot Be Inferred from Variance Component Analysis , 2016, bioRxiv.

[67]  E. Finnegan,et al.  Vernalization and the initiation of flowering , 1996 .

[68]  Ning Gao,et al.  Genomic prediction with epistasis models: on the marker-coding-dependent performance of the extended GBLUP and properties of the categorical epistasis model (CE) , 2017, BMC Bioinformatics.

[69]  I. Baldwin,et al.  Flower-specific jasmonate signaling regulates constitutive floral defenses in wild tobacco , 2017, Proceedings of the National Academy of Sciences.

[70]  T. Schnurbusch,et al.  The Genetic Architecture of Barley Plant Stature , 2016, Front. Genet..

[71]  Dabing Zhang,et al.  Roles of jasmonate signalling in plant inflorescence and flower development. , 2015, Current opinion in plant biology.

[72]  W Y Zhang,et al.  Discussion on `Sure independence screening for ultra-high dimensional feature space' by Fan, J and Lv, J. , 2008 .

[73]  P. L. Rodriguez,et al.  Negative Regulation of Abscisic Acid Signaling by the Fagus sylvatica FsPP2C1 Plays A Role in Seed Dormancy Regulation and Promotion of Seed Germination1 , 2003, Plant Physiology.

[74]  S. Clouse Plant development: A role for sterols in embryogenesis , 2000, Current Biology.

[75]  The effect of gene interactions on the long-term response to selection , 2016, Proceedings of the National Academy of Sciences.

[76]  J. J. Grant,et al.  CIPK3, a Calcium Sensor–Associated Protein Kinase That Regulates Abscisic Acid and Cold Signal Transduction in Arabidopsis Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.006858. , 2003, The Plant Cell Online.

[77]  G A Churchill,et al.  Genome-wide epistatic interaction analysis reveals complex genetic determinants of circadian behavior in mice. , 2001, Genome research.

[78]  Zitong Li,et al.  Estimation of Quantitative Trait Locus Effects with Epistasis by Variational Bayes Algorithms , 2012, Genetics.

[79]  G. Bolwell,et al.  Plant cytochrome P450. , 1994, Phytochemistry.

[80]  J. H. Moore,et al.  Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. , 2001, American journal of human genetics.