Origins and impacts of regulatory mutations

我们基于对大型DNA测序数据集的新计算分析，研究了DNA突变是如何导致出生缺陷和癌症的。总体而言，挑战是在许多影响基因功能并导致疾病的突变中找到一小部分突变。精子、卵子或早期胚胎的突变可能会导致儿童一系列罕见的遗传疾病，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，找到少数真正重要的突变，并帮助临床医生诊断病例。一个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组合是如何合作推动癌症生长的。这有助于将癌症患者与最有效的治疗方法相匹配，并可能建议对研究不足的肿瘤类型进行新的治疗。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关于人类疾病的基本新知识，但也为当前的医疗实践开辟了新的可能性。

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.