Comprehensive genetic dissection of a model highly complex trait in budding yeast

阐明基因和表型之间的联系对于在农业、进化生物学和医学上达到新的高度至关重要。在这个项目中，我们的目标是通过全面剖析“简单”模式生物体中的遗传复杂特征，来帮助描述基因-表型图谱背后的基本原理。具体地说，我们将扩大我们正在进行的关于酿酒酵母DNA损伤易感性的变异性的研究。我们将使用统计功能强大的高分辨率基因作图实验来识别导致三个菌株之间DNA损伤耐受性差异的数十个遗传变异。然后，我们将通过基因实验和功能分析来研究这些基因是如何相互作用并发挥作用的。我们的工作应该会产生迄今为止高度复杂特征的最详细的遗传特征之一，也可能为细胞如何检测和修复DNA损伤提供新的见解。作为我们对社会更广泛影响的一部分，我们将利用拟议的研究来培训多名博士、本科生和高中生。我们还将与在伯班克高中教授AP生物学四个部分的丽贝卡·库珀合作，开发多个实验室实践，在这些实践中，我们使用酵母中的可遗传性状变异来帮助向高中生教授生物学。与库珀？S女士的其他互动将包括与学生谈论科学领域的职业机会，以及讨论生物学研究对日常生活的诸多影响。最后，我们将把拟议的工作作为一种媒介，通过南加州大学的GREU计划让少数族裔接触到研究。

Elucidating the connection between genotype and phenotype is critical to achieving new heights in agriculture, evolutionary biology, and medicine. In this project, our goal is to help characterize basic principles underlying the genotype-phenotype map by comprehensively dissecting a genetically complex trait in a "simple" model organism. Specifically, we will extend our ongoing research on variability in susceptibility to DNA damage in Saccharomyces cerevisiae. We will use statistically powerful and high-resolution genetic mapping experiments to identify the dozens of genetic variants that cause differences in DNA damage tolerance among three strains. We will then study how these genes interact and exert their effects using genetic experiments and functional assays. Our work should produce one of the most detailed genetic characterizations of a highly complex trait to date, and could also provide new insights into how cells detect and repair DNA damage.As part of our broader impacts on society, we will use the proposed research to train multiple PhD, undergraduate, and high school students. We will also work with Rebecca Cooper, who instructs four sections of AP Biology at Burbank High School, to develop multiple lab practicals in which we use heritable trait variation in yeast to help teach biology to high school students. Additional interactions with Ms. Cooper?s class will involve talking with students about career opportunities in science, as well as discussing the many impacts of biological research on everyday life. Lastly, we will use the proposed work as a vehicle to expose minorities to research through the USC GREU program.