Creation of a Schwann Cell Gene Regulatory Network

雪旺细胞基因调控网络的创建

基本信息

批准号：
10581647
负责人：
John P Svaren
金额：
$ 18.11万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10581647
关键词：
Affect Binding Binding Sites Bioinformatics Cell Differentiation process ChIP-seq Charcot-Marie-Tooth Disease Code Collaborations Complex Computer Models Data Data Set Development Disease EGR2 gene Enhancers Gene Expression Regulation Gene Mutation Genes Genetic Genetic Transcription Genotype-Tissue Expression Project Goals Hereditary Disease Heritability Homeostasis Human Human Genome Individual Laboratories Link Maintenance Minority Modeling Molecular Mutation Myelin Myelin Sheath NR4A1 gene Nerve Nervous System Neural Crest Neuropathy Pathway interactions Patients Peripheral Nerves Peripheral Nervous System Peripheral Nervous System Diseases Peripheral nerve injury Predictive Value Process Publishing Regulatory Element Resolution Resources Role Schwann Cells Signal Transduction Site Testing Untranslated RNA Variant cell type computational pipelines epigenomics gene regulatory network genetic disorder diagnosis genetic variant genome sequencing improved in vivo loss of function myelination nervous system development nervous system disorder network models programs tool transcription factor transcription regulatory network whole genome

项目摘要

Abstract. The peripheral neuropathy known as Charcot-Marie-Tooth Disease (CMT1A) is one of the most common heritable disorders in the nervous system, affecting 1 in 2500 individuals. Tremendous progress has been made in identifying structural and coding variants that cause this disease, with over 100 genes having mutations associated with CMT. However, a substantial number of individuals do not have a definitive genetic diagnosis. The goal of this project is to develop a comprehensive Schwann cell gene regulatory network model incorporating experimental data on peripheral nerve with ChIP-seq analyses of TF binding as well as epigenomic annotations from human peripheral nerve that have recently become available. The model will incorporate data showing the dynamics of Schwann cell enhancers that have been shown to become dynamically regulated after peripheral nerve injury. Moreover, the model will be validated in its ability to identify key regulatory elements using eQTL analysis. Development of a Schwann cell network model with sufficient resolution to determine effects on individual enhancers and TF binding sites will be developed for eventual application to WGS analysis of patient data with peripheral neuropathy, including not only CMT but also other disorders affecting the peripheral nervous system.

抽象的。外周神经病称为charcot-marie-tooth病（CMT1A）是神经系统中最常见的可遗传障碍之一，影响1 2500个人。在识别结构和导致这种疾病的编码变体，超过100个具有突变的基因与CMT相关。但是，大量个人没有确定的遗传诊断。该项目的目标是开发一个全面的 Schwann细胞基因调节网络模型，结合了实验数据 TF结合以及表观基因组的CHIP-seq分析的周围神经最近可用的人类外周神经注释。这模型将合并数据，显示具有Schwann细胞增强器的动力学被证明是在周围神经损伤后动态调节的。而且，该模型将通过其使用EQTL识别关键调节元素的能力进行验证分析。开发具有足够解决的Schwann细胞网络模型确定对单个增强剂和TF结合位点的影响最终应用于周围神经病的患者数据的WGS分析，不仅包括CMT，还包括影响周围神经系统的其他疾病。