Origins and impacts of regulatory mutations

监管突变的起源和影响

• 批准号: MC_UU_00035/1
• 负责人: Colin Semple
• 金额: $ 307.59万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00035%2F1
• 关键词: Origins; impacts; regulatory; mutations

We study how alterations to DNA called mutations cause birth defects and cancers, based upon new computational analyses of large DNA sequencing datasets. Overall, the challenge is to find the small minority of mutations among many that affect gene functions and cause disease.Mutations in sperm, eggs or the early embryo can cause a huge range of rare genetic disorders in children, but the mutations underlying most cases are unknown. We aim to understand the processes that lead to these mutations as parents age, to find the few mutations that really matter, and help clinicians to diagnose cases.A tumour can accumulate many thousands of mutations in complex overlapping patterns, and we work to understand how combinations of mutations cooperate to drive cancer growth. This helps to match cancer patients to the most effective treatments, and may suggest new treatments in under-studied tumour types.Our work links diverse researchers, NHS clinical staff and industry in multidisciplinary research that generates important new data as well as extracting new insights from existing data. Our projects are designed to reveal fundamental new knowledge about human disease, but also to open new possibilities in current medical practice.

我们研究DNA的改变（称为突变）如何导致出生缺陷和癌症，基于对大型DNA测序数据集的新计算分析。总的来说，挑战在于在众多影响基因功能并导致疾病的突变中，找到那一小部分。精子、卵子或早期胚胎中的突变可能会导致儿童出现大量罕见的遗传疾病，但大多数病例背后的突变尚不清楚。我们的目标是了解随着父母年龄的增长导致这些突变的过程，找到真正重要的少数突变，并帮助临床医生诊断病例。肿瘤可以以复杂的重叠模式积累数千个突变，我们致力于了解突变的组合如何协同驱动癌症生长。这有助于为癌症患者匹配最有效的治疗方法，并可能为研究不足的肿瘤类型提供新的治疗方法。我们的工作将不同的研究人员、NHS临床工作人员和行业联系在一起，进行多学科研究，产生重要的新数据，并从现有数据中提取新的见解。我们的项目旨在揭示有关人类疾病的基本新知识，同时也为当前的医疗实践开辟新的可能性。

项目成果

Divergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer

结构多样性的不同轨迹影响高级别浆液性卵巢癌患者的生存

• DOI: 10.1101/2024.01.12.575376
• 发表时间: 2024
• 作者: Ewing A