GENOME WIDE ASSOCIATION MAPPING IN ARABIDOPSIS THALIANA

描述（由申请人提供）： 我们的计划将调查的遗传和分子基础的复杂的表型及其环境效应的模式植物拟南芥。我们将实现一个新的，多用途，高密度寡核苷酸平铺阵列粗糙基因组重测序和公正的转录研究。对384株野生A.将利用拟南芥基因组绘制第一个高分辨率全基因组单倍型图。这将揭示基因组范围内的变异模式，并提出自然选择的位点。开花时间和幼苗伸长的生态相关的数量性状将在两个季节和两个地理环境中测量，跨越A的本地范围。thaliana.这和其他可用的数据将用于精细尺度的数量性状基因座（QTL）的关联扫描对单倍型图。我们将利用拟南芥遗传学的全部力量来确定两个新QTL的功能分子变化。基因表达的自然变异将揭示对季节和地理环境的转录反应的遗传控制，并确定上游候选基因和下游信号组分。深入研究正反交杂种间等位基因变异基因表达，将揭示印记和顺式调控变异。这项工作扩展了以前的研究自然变化的光和开花反应在拟南芥。重要的是，新的技术道路将铺平使用全基因组平铺阵列，以产生高密度单倍型地图扩展到人类和哺乳动物模型系统。这些数据集将是一个试验场的精细规模连锁不平衡映射方法，也是广泛适用的发展。人们对人类复杂的疾病关联图谱有着极大的兴趣，但对不同方法的争论很多，迄今为止几乎没有成功。在拟南芥中提出的研究将为这项艰巨的任务提供成功的途径，因为可以快速确认关联以识别新的QTL。

DESCRIPTION (provided by applicant): 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.