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

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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.