GENOME WIDE ASSOCIATION MAPPING IN ARABIDOPSIS THALIANA

拟南芥全基因组关联图谱

• 批准号: 7255051
• 负责人: JUSTIN O BOREVITZ
• 金额: $ 3.25万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255051
• 关键词: GENOME; WIDE; ASSOCIATION; MAPPING; ARABIDOPSIS

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.

描述（由申请人提供）： 我们的提案将研究模式植物拟南芥中复杂表型的遗传和分子基础及其环境影响。我们将实施一种新的、多用途、高密度寡核苷酸平铺阵列，用于粗略的基因组重测序和公正的转录研究。对 384 个野生拟南芥基因组的重新测序将用于开发第一个高分辨率全基因组单倍型图谱。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。将在跨越拟南芥原生范围的两个季节和两个地理环境中测量开花时间和幼苗伸长的生态相关数量性状。该数据和其他可用数据将用于针对单倍型图谱进行精细数量性状基因座 (QTL) 关联扫描。我们将利用拟南芥遗传学的全部力量来确定两个新 QTL 背后的功能分子变化。基因表达的自然变异将揭示转录反应对季节和地理环境的遗传控制，并识别上游候选基因和下游信号成分。深入关注互杂种之间的等位基因变异基因表达将揭示印记和顺式调控变异。这项拟议的工作扩展了先前对拟南芥中光和开花反应的自然变化的研究。重要的是，将为使用全基因组平铺阵列生成可扩展到人类和哺乳动物模型系统的高密度单倍型图谱铺平新技术道路。这些数据集将成为开发也广泛适用的精细尺度连锁不平衡作图方法的试验场。人们对人类复杂疾病关联图谱有着极大的兴趣，但对不同方法的争论很多，但迄今为止收效甚微。本文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。