Developing a resource for investigations into the penetrance of disease-causing genomic variants

“我的病会发展到多严重？”“我的视力还能维持多久？”“我的哥哥和父亲在20岁时失明了，我也会吗？”“基因检测已经彻底改变了患有罕见和遗传性疾病的人的诊断和管理方式，但是这些重要的问题经常被世界各地的眼科基因诊所的患者提出，随着基因检测的可用性和可及性的增加，这些问题将变得更加频繁。”然而，作为一个科学界，我们几乎没有强有力的答案来解释为什么尽管在他们的DNA中遗传了同样的导致疾病的拼写错误——突变——儿子/女儿患疾病的程度可能比他们的父亲轻，或者在某些情况下根本没有。通过与Sano Genetics的合作，我们将开发丰富的临床信息和生物样本资源，以帮助我们在这方面的研究。我们预计这项工作将加速我们了解额外的基因变化影响疾病表现和严重程度的方式，并开发对遗传性眼病患者的临床管理立即有用的信息。该项目将为跨不同临床专业提出这些类型的复杂科学问题所需的资源开发一个框架。

'How severely will my disease develop?''How long will I have my sight for?''My brother and father lost their sight at 20, will I as well?'Genetic testing has revolutionised the way that individuals with rare and inherited diseases can be diagnosed and managed, but these important questions are frequently asked by patients in eye genetic clinics across the world and will become more frequent as the availability and accessibility to genetic testing increases. However, as a scientific community we have very few robust answers as to why despite inheriting the same disease-causing spelling mistakes in their DNA - mutations - a son/daughter may develop disease less severely than their father, or in some cases not at all. Through partnership with Sano Genetics, we will develop a resource which is rich in appropriate clinical information and biological samples to help our investigations in this regard. We anticipate that this work will accelerate our knowledge of the way that additional genetic changes impact the presentation and severity of disease, and develop information which is immediately useful for the clinical management of individuals with genetic eye conditions. The project will develop a framework for the resources required to ask these types of complex scientific questions across different clinical specialities.