Phenotyping and In Silico Mapping of Quantitative Traits

CGD教师先前的工作已经建立了数量性状基因座（QTL）的两个关键特性。 第一，它们只代表了一个复杂性状所需的全部基因的一个子集， 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通常位于同源位点， 人类、小鼠和大鼠的染色体定位。对这些发现的一个可能解释是， 代表其作用在哺乳动物进化过程中一直保守的关键调节功能。 鉴于各种表型的QTL是造成大部分群体变异的原因， 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可能与以下基因连锁： 促进有利等位基因组合的共遗传。这个项目的假设是， 结构域是哺乳动物染色体组织的一般特征， 影响表型的QTL。严格检验这一假设需要我们有效地定位QTL在一个特定的位置， 在小鼠亚种的多样性中，分辨率为几Mb或更低。

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.