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Contribution of variants in non-protein coding regions of the genome to human health and disease

基因组非蛋白质编码区变异对人类健康和疾病的贡献

基本信息

批准号：
2776425
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2776425
关键词：
Contribution variants non protein coding

项目摘要

The aim of this project is to reveal the contribution of variants in the non-coding regions of the genome to human genetic disorders. Objectives and methods: 1. Understanding the landscape of variability of the regulome: The student will define 'regulomes' for a range of human tissues by integrating publicly available epigenomic, regulatory, and transcriptomic data. Then areas of the these regulomes that are most depleted for genetic variations in the humans will be ranked using population variant frequencies and integrated with evolutionary conservation data. We hypothesise that this will predict regions of the regulomes enriched for disease-causing variants in patients. 2. Identifying human disease-causing variants in the regulome: The student will interrogate whole genome databases from patients (e.g. the 100,000 Genomes project) to identify variants within the critical regions of the regulome curated in Objective 1. Correlations with clinical features, information from the segregation of the variants within families and the predicted/known functions of the regulatory region will be used to prioritise the variants that are highly likely to be responsible for the patients' diseases. 3. Studying the functional impact of disease-causing regulatory variants: Depending on the predicted impact of the variant, targeted (e.g. QPCR) or high-throughput (e.g. RNASeq, Hi-C, dropSeq) assays will be performed either using patient samples or cell lines. This will allow functional interrogation of the variants. Finally these results will be linked back with the clinical data. Outcome: We expect this project to make major contributions to our understanding of the role of variants in the non-coding genome on human health and disease. The project is expected to result in high-impact publication(s).

该项目的目的是揭示基因组非编码区变异对人类遗传疾病的贡献。目的与方法：1。了解规则组的可变性景观：学生将通过整合公开的表观基因组，监管和转录组数据来定义一系列人体组织的“规则组”。然后，将使用群体变异频率对人类遗传变异最耗尽的这些调节组的区域进行排名，并与进化保守数据相结合。我们假设这将预测患者中富含致病变异的调节组区域。2.识别调节组中的人类致病变体：学生将询问患者的全基因组数据库（例如100，000基因组项目），以识别目标1中策划的调节组关键区域内的变体。与临床特征的相关性、来自家族内变体分离的信息以及调控区的预测/已知功能将用于优先考虑极有可能导致患者疾病的变体。3.研究致病性调控变体的功能影响：根据变体的预测影响，将使用患者样本或细胞系进行靶向（例如QPCR）或高通量（例如RNASeq、Hi-C、dropSeq）测定。这将允许变体的功能询问。最后，这些结果将与临床数据联系起来。结果：我们希望这个项目能为我们理解非编码基因组中变异对人类健康和疾病的作用做出重大贡献。预计该项目将产生影响力大的出版物。