Elucidating the genetic architecture of cystic kidney disease using whole-genome sequencing

囊性肾脏疾病，包括多囊肾疾病，在英国肾衰竭中占很大比例，通常在家族中发生，通常是由于基因的变化(生物体用来建立和维持健康功能的指令)。然而，并不是每个患有囊性肾病的人都会患上肾衰竭，这种差异性的原因目前还不太清楚。这个项目将使用1200多个囊性肾病家庭的整个基因组(即所有基因)测序的数据，以及详细的临床信息，如哪些其他器官受到影响，以及是否以及何时发生肾衰竭。在300多个家庭中，将获得关于识别基因变化是否以及如何影响临床管理的详细信息。这将揭示基因组测序在诊断患者囊性肾脏疾病原因方面的效用和好处，并将为每种类型的基因变化的后果和严重性提供新的见解。先前的研究表明，在患有多囊肾病的家庭中，大约10%的家庭无法确定与此相关的基因。通过使用与大量没有肾脏疾病的人的基因组序列的比较，该项目处于独特的地位，可以识别以前不被认为与囊性肾脏疾病有关的基因变化，为肾囊肿的形成和发展提供新的见解，可能导致新的治疗方法。

Cystic kidney diseases, including polycystic kidney disease, account for a significant proportion of kidney failure in the UK, often run in families and usually result from a change in a gene (instructions that organisms use to establish and maintain healthy function). However, not everyone with cystic kidney disease will develop kidney failure and the reasons for this variability are poorly understood.This project will use data from sequencing the whole genomes (i.e. all the genes) of over 1200 families with cystic kidney disease along with detailed clinical information, such as which other organs are affected and whether and when kidney failure developed. In over 300 of the families, detailed information will be available on whether and how identifying the genetic change influenced clinical management. This will reveal the utility and benefits of genome sequencing to diagnose the cause of cystic kidney disease in patients and will provide new insights into the consequences and severity of each type of gene change. Previous studies have shown that in around 10% of families with polycystic kidney disease the gene responsible cannot be identified. By using comparisons with genome sequences from large numbers of people without kidney disease, this project is uniquely placed to identify changes in genes not previously thought to be involved in cystic kidney disease, providing new insights into how kidney cysts form and develop, potentially leading to new treatments.