DISSERTATION RESEARCH: Modularity of Pleiotropic Effects on Skeletal Morphology.

许多生物学上重要的特征，包括疾病、大小和形状，都受到多种基因的影响。这个项目将定位和鉴定影响骨骼大小和形状的基因。我们预测，受共同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，而受不同过程影响的性状将受到不同基因集的影响。例如，股骨和胫骨是分开的骨骼，但它们是由后肢芽的共同生长产生的，所以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中影响整个骨骼分布的68个骨骼特征的位置，并检查了一个层次模块化结构的基因效应的常见模式。将对2250只老鼠的骨骼和特征进行数码照片拍摄，并使用数码图像分析软件进行测量。基因组中影响这些性状的位置将被统计学地识别出来。最初的基因定位之后是选定的基因组位置的更精细的地图，以确定所涉及的特定基因。该项目将促进对骨骼大小和形状方面的模块化遗传学及其对人口过程的影响的理解。它还创建了一个包含5万张骨骼数字图像的DVD存档资源，供其他研究人员使用。骨和生长相关疾病的生物医学研究和治疗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.