Phenotyping and In Silico Mapping of Quantitative Traits

数量性状的表型分析和计算机绘图

• 批准号: 7299597
• 负责人: Beverly J Paigen
• 金额: $ 16.08万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7299597
• 关键词: biochemical evolution; bioinformatics; computational biology; functional /structural genomics; genetic strain; laboratory mouse; phenotype; quantitative trait loci

Previous work by CGD faculty has established two critical properties of quantitative trait loci (QTL). First, they represent only a sub-set of the totality of genes functionally required for a complex trait such as the regulation of blood pressure or relative susceptibility to atherosclerosis. And second, the same sub-set of genes determine QTLs across mammalian species. QTLs for a given trait are often located at homologous chromosomal locations in human, mouse and rat. A probable explanation for these findings is that QTLs represent key regulatory functions whose role has been conserved over the course of mammalian evolution. Given that the QTLs for various phenotypes are responsible for most of the population variation on which evolution can act and that the identity of these QTL is an ancient property of mammals, genome dynamics predicts that the QTLs for fundamental physiological properties are likely to be genetically linked to promote the co-inheritance of favorable allelic combinations. The hypothesis of this project is that functional domains are a general feature of mammalian chromosomal organization and will be revealed by the clustering of QTLs affecting a phenotype. Rigorously testing this hypothesis requires that we efficiently locate QTLs at a resolution of a few Mb or less across the diversity of Mus subspecies.

CGD 教师之前的工作已经确定了数量性状基因座 (QTL) 的两个关键特性。 首先，它们仅代表复杂性状功能所需的全部基因的子集，例如 调节血压或对动脉粥样硬化的相对易感性。其次，相同的子集 基因决定哺乳动物物种的 QTL。给定性状的 QTL 通常位于同源位置 人类、小鼠和大鼠的染色体位置。对这些发现的一个可能的解释是 QTL 代表了关键的调节功能，其作用在哺乳动物的进化过程中一直得到保留。 鉴于不同表型的 QTL 是造成大多数群体变异的原因。 进化可以发挥作用，并且这些 QTL 的身份是哺乳动物、基因组的古老属性 动力学预测基本生理特性的 QTL 可能与 促进有利等位基因组合的共同遗传。该项目的假设是功能 结构域是哺乳动物染色体组织的一般特征，将通过聚类来揭示 影响表型的 QTL。严格检验这一假设需要我们有效地将 QTL 定位在 Mus 亚种多样性的分辨率为几 Mb 或更低。