Approved Research

Leveraging large genome sequencing datasets to enhance the interpretation of rare genomic variants in developmental disorders

Lay summary

Up to 1 in 20 children are born with a "spelling change" in their genes which has a severe impact on their growth, health and development. These conditions are called "developmental disorders". Although each of them is rare, together they are a leading cause of death in young children.

New technology means we can now read all of the spelling changes in a person's genes. But although we can read them, we can't always understand them. This is a big problem for many children with developmental disorders. About half of children with these disorders don't get a diagnosis. Although we may think they have a genetic condition, often we don't know which of their spelling changes is the cause.

For example, the effect of spelling changes at the far end of genes can be unclear. This is because of the different way in which the far ends of the genes are read and processed in our cells. We want to look at these spelling changes at the far end of genes to find out what makes them different. Hopefully we will be able to find new diagnoses for patients with these conditions, and learn more about the biology of rare genetic diseases.

These discoveries can be the first step to understand how and why certain spelling changes cause developmental disorders. In turn, we hope this knowledge will help us find new treatments for these disorders.

The UK Biobank data is very helpful to this research. This might be surprising, because there are no people with severe developmental  disorders in the UK Biobank. Instead, we will look at genetic spelling changes found in people in the UK Biobank, and compare these to spelling changes in people with developmental disorders. This will help us to decide which changes are more likely, or less likely, to cause developmental disorders.

We hope that using the UK Biobank data will help us to find new diagnoses for sick children, and learn more about the biology of rare genetic diseases.