title: Combining genome-wide association mapping and transcriptional networks to identify novel genes controlling glucosinolates in Arabidopsis thaliana.
abstract: BACKGROUND
  Genome-wide association (GWA) is gaining popularity as a means to study the architecture of complex quantitative traits, partially due to the improvement of high-throughput low-cost genotyping and phenotyping technologies. Glucosinolate (GSL) secondary metabolites within Arabidopsis spp. can serve as a model system to understand the genomic architecture of adaptive quantitative traits. GSL are key anti-herbivory defenses that impart adaptive advantages within field trials. While little is known about how variation in the external or internal environment of an organism may influence the efficiency of GWA, GSL variation is known to be highly dependent upon the external stresses and developmental processes of the plant lending it to be an excellent model for studying conditional GWA.
  
  
  RESULTS
  To understand how development and environment can influence GWA, we conducted a study using 96 Arabidopsis thaliana accessions, >40 GSL phenotypes across three conditions (one developmental comparison and one environmental comparison) and ∼230,000 SNPs. Developmental stage had dramatic effects on the outcome of GWA, with each stage identifying different loci associated with GSL traits. Further, while the molecular bases of numerous quantitative trait loci (QTL) controlling GSL traits have been identified, there is currently no estimate of how many additional genes may control natural variation in these traits. We developed a novel co-expression network approach to prioritize the thousands of GWA candidates and successfully validated a large number of these genes as influencing GSL accumulation within A. thaliana using single gene isogenic lines.
  
  
  CONCLUSIONS
  Together, these results suggest that complex traits imparting environmentally contingent adaptive advantages are likely influenced by up to thousands of loci that are sensitive to fluctuations in the environment or developmental state of the organism. Additionally, while GWA is highly conditional upon genetics, the use of additional genomic information can rapidly identify causal loci en masse.
authors.affiliation: Department of Plant Sciences, University of California-Davis, Davis, California, United States of America.
authors.forename: Eva K F
authors.initials: EK
authors.lastname: Chan
authors.forename: Heather C
authors.initials: HC
authors.lastname: Rowe
authors.forename: Jason A
authors.initials: JA
authors.lastname: Corwin
authors.forename: Bindu
authors.initials: B
authors.lastname: Joseph
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kliebenstein
mesh_terms: D017360:Arabidopsis / Q000235:genetics*; D002874:Chromosome Mapping; D055106:Genome-Wide Association Study / Q000379:methods*; D005961:Glucosinolates / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics
chemical_list: D005961:Glucosinolates