Genomic Analysis of the genotype-phenotype map

基因型-表型图谱的基因组分析

• 批准号: 7918283
• 负责人: Simon Tavare
• 金额: $ 233.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7918283
• 关键词: Genomic; Analysis; genotype; phenotype; map

DESCRIPTION (provided by applicant): This proposal is for the renewal of our existing Center of Excellence in Genomic Science ("Implication of Haplotype Structure in the Human Genome"). Since the start of our Center in 2003, there have been extraordinary advance in genomics. Genome-wide association studies using Single Nucleotide Polymorphisms are now routine, and we are rapidly moving toward having whole-genome sequence data for large samples of individuals. Our Center has undergone similar dramatic change. While the underlying theme of our proposal remains the same - making sense of genetic variation - our focus is now explicitly on how we can use the heterogeneous data produced by modern genomics to achieve such an understanding. The overall goal of our proposal is to develop an intellectual framework, together with computational and statistical analysis tools, for illuminating the path from genotype to phenotype, and for predicting the latter from the former. We will address three broad questions related to this problem: 1) How do we infer mechanisms by which genetic variation leads to changes in phenotype? 2) How do we improve the design, understanding and interpretation of association studies by exploiting prior information? 3) How do we identify general principles about the genotype-phenotype map? We will approach these questions through a series of interrelated projects that combine computational and experimental methods, and involve a wide range of researchers including molecular biologists, population geneticists, genetic epidemiologists, statisticians, computer scientists, and mathematicians. PUBLIC HEALTH RELEVANCE - One of the most important challenges facing biology today is understanding how genetic variation between individuals translates (or maps) into variation we can see or measure, like blood pressure, and how this mapping is affected by the environment. The goal of this project is to increase our understanding of the general principles that underlie the genotype-phenotype map by studying model organisms.

描述（由申请人提供）：该提案旨在更新我们现有的基因组科学卓越中心（“人类基因组中单倍型结构的含义”）。自 2003 年我们中心成立以来，基因组学领域取得了非凡的进步。使用单核苷酸多态性的全基因组关联研究现已成为常规，我们正在迅速朝着获得大样本个体的全基因组序列数据的方向发展。我们的中心也经历了类似的巨大变化。虽然我们提案的基本主题保持不变——理解遗传变异——但我们现在的重点明确是如何使用现代基因组学产生的异质数据来实现这种理解。我们提案的总体目标是开发一个知识框架，以及计算和统计分析工具，以阐明从基因型到表型的路径，并从前者预测后者。我们将解决与该问题相关的三个广泛问题：1）我们如何推断遗传变异导致表型变化的机制？ 2）我们如何通过利用先验信息来改进关联研究的设计、理解和解释？ 3）我们如何确定基因型-表型图谱的一般原则？我们将通过一系列相互关联的项目来解决这些问题，这些项目结合了计算和实验方法，并涉及广泛的研究人员，包括分子生物学家、群体遗传学家、遗传流行病学家、统计学家、计算机科学家和数学家。 公共卫生相关性——当今生物学面临的最重要挑战之一是了解个体之间的遗传变异如何转化（或映射）为我们可以看到或测量的变异，例如血压，以及这种映射如何受到环境的影响。该项目的目标是通过研究模式生物来加深我们对基因型-表型图谱基础一般原理的理解。