? Our proposal will investigate the genetic and molecular basis of complex phenotypes and their environmental effects in the model plant Arabidopsis thaliana. We will implement a new, multi use, high density oligonucleotide tiling array for rough genome resequencing and unbiased transcriptional studies. The resequencing of 384 wild A. thaliana genomes will be used to develop the first high resolution whole genome haplotype map. This will reveal genome wide patters of variation and suggest sites of natural selection. The ecologically relevant quantitative traits of flowering time and seedling elongation will be measured across two seasonal and two geographic environments which span the native range of A. thaliana. This and other available data will be used for fine scale quantitative trait locus (QTL) association scanning against the haplotype map. We will determine the functional molecular changes underlying two novel QTL utilizing the full power of Arabidopsis genetics. Natural variation in gene expression will reveal genetic control of transcriptional response to seasonal and geographic environments and identify upstream candidate genes and downstream signaling components. An in depth focus on allelic variation gene expression among reciprocal hybrids will reveal imprinting and cis regulatory variation. This proposed work extends prior studies of natural variation in light and flowering response in Arabidopsis. Importantly, new technological roads will be paved for using whole genome tiling arrays to generate high density haplotype maps extendible to humans and mammalian model systems. These data sets will be a testing ground for the development of fine scale linkage disequilibrium mapping methods that are also broadly applicable. There is a tremendous interest in complex disease association mapping in humans, 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 #
3R01GM073822-01A1S1
Application #
7255051
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
2006-03-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$32,474
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
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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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