Phenotyping and In Silico Mapping of Quantitative Traits

CGD教授以前的工作已经建立了数量性状基因座(QTL)的两个关键属性。 首先，它们只代表复杂性状所需的全部基因的一个子集，如 调节血压或对动脉粥样硬化的相对易感性。第二，相同的子集 基因决定哺乳动物物种间的QTL。一个给定性状的QTL通常位于同源 人、小鼠和大鼠的染色体定位。对这些发现的一个可能解释是，QTL 代表关键的调节功能，其作用在哺乳动物进化过程中一直是保守的。 考虑到不同表型的QTL是造成群体差异的主要原因 哪些进化可以起作用，这些QTL的身份是哺乳动物的一种古老属性，基因组 Dynamic预测，基本生理特性的QTL很可能与遗传相关 促进有利等位基因组合的共遗传。这个项目的假设是功能性的 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。严格检验这一假说需要我们有效地定位QTL 在小鼠亚种的多样性中分辨率只有几个Mb或更少。

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.