Genetic Architecture and Developmental Consequences of Conditionally Functional Mutations

项目摘要 大多数特征，包括复杂的疾病，如糖尿病，精神疾病和心血管疾病， 有很强的遗传成分。然而，个体等位基因如何影响性状表达可能取决于 其他基因座上的基因型，或者环境方面。拟议的研究旨在阐明 条件功能突变在决定复杂性状中的程度和性质， 使用发育和遗传模式生物C.优雅这条蠕虫很容易感染- 通量，自动化表型分析方法，其允许足够的复制以检测 天然等位基因变体的潜在微妙影响。因此，这项工作利用了 一个实验模型系统，询问有关自然遗传的功能后果的问题， 变化量通过研究定量和模型系统遗传学的接口，本研究旨在 提高我们对复杂特质结构的理解，并提供新的见解， 基因型和表型之间的遗传和发育机制。

Project Summary Most traits, including complex diseases like diabetes, psychiatric disorders and cardiovascular disease, have a strong genetic component. However, how individual alleles affect trait expression may depend on genotypes at other loci, or on aspects of the environment. The proposed research seeks to elucidate the extent and nature of conditionally functional mutations in the determination of complex traits, using the developmental and genetic model organism C. elegans. This worm is amenable to high- throughput, automated phenotyping methodologies, which permit sufficient replication to detect the potentially subtle effects of natural allelic variants. Thus, the work leverages the resources in an experimental model system to ask questions about the functional consequences of natural genetic variation. By working at the interface of quantitative and model system genetics, this research aims to improve our understanding of complex trait architecture as well as provide new insight into the genetic and developmental mechanisms that lie between genotype and phenotype.