Disease Modeling Core

下一代测序（NGS）技术的出现使得有可能鉴定完整的DNA序列。 单个个体的遗传变异谱。这使得有可能识别出罕见的变异， 导致人类遗传疾病。然而，这很快就产生了一种需要， 证明候选基因是因果关系。开始理解特定遗传的一种机制 PD病理生理学背景下的变化是为了确定表达变化的影响， 的候选基因在关键的细胞通路、分子功能和调控网络上， 称为路径分析。通过研究特定候选基因的敲除或击倒 我们就可以开始找出导致疾病的关键途径 表型为此，建立了一个综合的多生物体疾病建模核心， 在酵母、斑马鱼和诱导多能干细胞（IPSC）建模方面的专业知识。每个模型 核心中的有机体代表了不同层次的复杂性，可以用来更好地理解 PD病理学的不同方面。这一核心将有助于迅速查明 研究特定基因功能丧失的影响的适当模型（来自项目1 和3）和非编码RNA（项目2）对转录组的影响（在核心C中分析）。敲减或 将在适当的生物体中开发特定候选基因的敲除模型， 用于转录组分析的生物材料（总RNA）。除了提供总RNA外， 敲除/敲低细胞和组织（以及控制细胞和组织），这个核心将产生重要的 试剂（吗啉代，shRNA，酵母敲除菌株和iPSC）用于未来的功能研究， 为UM Udall中心的成员以及其他Udall中心和PD研究人员提供PD病理学。

The advent of next generation sequencing (NGS) technologies has made it possible to identify the full spectrum of genetic variations in single individuals. This has made it possible to identify rare variants that contribute to human genetic diseases. However, this has quickly created a need for mechanisms to prove or demonstrate that the candidate genes are causal. One mechanism to begin to understand specific genetic variations in the context of the pathophysiology of PD is to identify the impact that changes in the expression of the candidate genes have on key cellular pathways, molecular functions and regulatory networks, so called pathway analysis. By examining the effect that the knockout or knockdown of specific candidate genes have on the transcriptome, we can begin to identify the key pathways responsible for the disease phenotype. To that end, an integrated, multi-organism disease modeling core has been established to bring together expertise in yeast, zebrafish and induced pluripotent stem cells (IPSCs) modeling. Each model organism in the core represents a different level of complexity and can be used to better understand different aspects of the pathology of PD. This core will facilitate the rapid identification of the most appropriate models for examining the impact that loss of function of specific genes (derived from Project 1 and 3) and non-coding RNAs (Project 2) have on the transcriptome (analyzed in Core C). Knockdown or knockout models of the specific candidate genes will be developed in the appropriate organisms to provide the biological material (total RNA) for transcriptome analysis. In addition to providing total RNA from the knockout/knockdown cells and tissues (and control cells and tissues), this core will generate important reagents (morpholinos, shRNAs, yeast knock strains and iPSCs) for future functional studies into the pathology of PD for members of the UM Udall Center, as well as, other Udall Centers and PD investigators.