Our proposalwill investigate the genetic and molecular basis of complex traits and their interactions with the environment using the model plant Arabidopsis thaliana. We will implement a multi use, high density oligo- nucleotide tiling array for whole genome resequencing. The sample will include a largely unstructured core set of 384 wild A. thaliana genomes. This will be usedto develop a very high resolution haplotype map, reveal genome wide patterns of variation, and suggest sites under natural selection. The ecologically relevant quantitative traits of flowering time and seedling elongation light response will be measured across two seasonal and two geographic environments which span the native range of A. thaliana. This and future community phenotypic data will be used to develop and test methods for fine scale quantitative trait locus (QTL) association scanning capitalizing on the high density haplotype map. Whole genomeassociation mapping will be developed using coalescent models for detection and fine mapping. We will determine the functional molecular changes underlying two novel QTL utilizing the full powerof Arabidopsis genetics. Importantly this proposal will develop newtechnological inroads for using tiling arrays to generate high density haplotype maps as the foundation for whole genome association studies. These methods, once established, can then be extended to other model systems. The development of fine scale linkage disequilibrium mapping methodswill be broadly applicable. There is a tremendous interest in complex disease association mapping, but much debate over different approaches and little success to date. The studies proposed here in Arabidopsis will suggest successful paths for this daunting undertaking, as associations can be quickly confirmed to identify novel QTL.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM073822-03
Application #
7367934
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2006-03-01
Project End
2011-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
3
Fiscal Year
2008
Total Cost
$469,620
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Brachi, Benjamin; Morris, Geoffrey P; Borevitz, Justin O (2011) Genome-wide association studies in plants: the missing heritability is in the field. Genome Biol 12:232
Zhang, Xu; Cal, Andrew J; Borevitz, Justin O (2011) Genetic architecture of regulatory variation in Arabidopsis thaliana. Genome Res 21:725-33
Brachi, Benjamin; Faure, Nathalie; Horton, Matt et al. (2010) Linkage and association mapping of Arabidopsis thaliana flowering time in nature. PLoS Genet 6:e1000940
Atwell, Susanna; Huang, Yu S; Vilhjálmsson, Bjarni J et al. (2010) Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. Nature 465:627-31
Li, Yan; Huang, Yu; Bergelson, Joy et al. (2010) Association mapping of local climate-sensitive quantitative trait loci in Arabidopsis thaliana. Proc Natl Acad Sci U S A 107:21199-204
Platt, Alexander; Horton, Matthew; Huang, Yu S et al. (2010) The scale of population structure in Arabidopsis thaliana. PLoS Genet 6:e1000843
Zollner, Sebastian (2010) CopyMap: localization and calling of copy number variation by joint analysis of hybridization data from multiple individuals. Bioinformatics 26:2776-7
Todesco, Marco; Balasubramanian, Sureshkumar; Hu, Tina T et al. (2010) Natural allelic variation underlying a major fitness trade-off in Arabidopsis thaliana. Nature 465:632-6

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