DISSERTATION RESEARCH: Modularity of Pleiotropic Effects on Skeletal Morphology.

许多生物学上重要的性状，包括疾病、大小和形状，都受到多个基因的影响。 该项目将定位和识别影响骨骼大小和形状的基因。 我们预测，受共同的发育和功能过程影响的小鼠骨骼性状将共享共同的基因效应，受不同过程影响的性状将受到不同基因组的影响。 例如，股骨和胫骨是独立的骨骼，但它们是由后肢芽的共同生长产生的，因此我们预计这些骨骼的变异会受到许多相同基因的影响。 在这个项目中，我们调查了小鼠基因组的位置影响68骨骼特征分布在整个骨骼和研究基因效应的层次，模块化结构的共同模式。 将拍摄2250只小鼠骨骼的数字照片，并使用数字图像分析软件测量特征。 基因组中影响这些性状的位置将通过统计学方法确定。 最初的基因定位是由选定的基因组位置，以确定具体的基因比例尺的地图。该项目将推进骨骼大小和形状方面的模块化遗传学的理解及其对人口过程的后果。 它还创建了一个由50，000个骨骼数字图像组成的资源，这些图像存档在DVD上，可供其他研究人员使用。生物医学研究和治疗骨骼和生长相关疾病也可能在未来从这项工作中发展。因此，该项目还研究了复杂性状遗传学的理论方面，从而也有助于健康相关的研究。

Many biologically important traits, including disease and size and shape, are influenced by multiple genes. This project will locate and identify genes affecting skeletal size and shape. We predict that mouse skeletal traits affected by common developmental and functional processes will share common gene effects and that traits affected by different processes will be affected by distinct sets of genes. For example, the femur and tibia are separate bones but are produced by the common outgrowth of the posterior limb bud so we expect variation in these bones to be affected by many of the same genes. In this project we survey the mouse genome for locations affecting 68 skeletal traits distributed throughout the skeleton and examine common patterns of gene effects for a hierarchical, modular structure. Digital photographs will be taken of 2250 mouse skeletons and traits measured using software for analyzing digital images. Locations in the genome that affect these traits will be identified statistically. Initial gene mapping is followed by a finer-scale map of selected genomic locations to identify the specific genes involved.This project will advance the understanding of the genetics of modularity for aspects of skeletal size and shape and its consequences for population processes. It also creates a resource of 50,000 skeletal digital images archived on DVD that will be available to other researchers. Biomedical studies and treatments for bone and growth-related diseases may also develop from this work in the future. Thus, this project also investigates theoretical aspects of the genetics of complex traits, thus contributing to health-related research as well.