MIRA: Systems genomics of complex traits - Administrative Supplements to Support Undergraduate Summer Research Experiences

项目总结： 人类的基因-表型图谱是由多种基因之间复杂的相互作用形成的 基因座和环境因素，但这些相互作用的结构和功能仍然很差 明白了。这种缺乏理解限制了我们预测和预防个人的能力 对疾病和疾病的敏感性。 这些相互作用可以产生多效性效应，使传统的基因敲除感到困惑。 接近了。此外，基因组环境可以在功能上调节这些相互作用 从进化的角度来看。我们的目标是用系统遗传学框架来阐明这些问题。 秀丽隐杆线虫及其近缘的三种实验范式：(1)如何 复杂的监管系统的演变和功能？(2)来源和后果是什么？ 基因组超多样性？以及(3)变异、重组和有性繁殖是如何 会影响进化反应吗？我们将采用一种综合的方法，结合基因组学， 单细胞分析、微流控工程、高通量表型、遗传学 变形学和计算生物学。这项研究结合了强大的功能 应用系统遗传学的自然遗传变异假设检验框架 帮助了解复杂监管系统的演变和功能的方法 对人类健康有至关重要的影响。

Project Summary: The genotype-phenotype map in humans is shaped by complex interactions between multiple loci and environmental factors, but the structure and function of these interactions remain poorly understood. This lack of understanding limits our ability to predict and prevent individual susceptibility to sickness and disease. These interactions can generate pleiotropic effects that confound traditional knockout approaches. Moreover, the genomic context can modulate these interactions both functionally and evolutionarily. We aim to elucidate these questions using a systems-genetics framework with three experimental paradigms in Caenorhabditis elegans and its relatives: (1) How do complex regulatory systems evolve and function? (2) What are the sources and consequences of genomic hyper diversity?, and (3) How do variation, recombination and sexual reproduction affect evolutionary responses? We will employ an integrative approach that combines genomics, single-cell analysis, microfluidic engineering, high-throughput phenotyping, genetic transformation, and computational biology. This research combines a strong functional hypothesis-testing framework with natural genetic variation to apply a systems-genetics approach that helps understand the evolution and function of complex regulatory systems that have critical implications for human health.