Mapping the rules of translation initiation and the pathogenicity of start-site variants

Summary

This project will help us to better understand how the fundamental biological process, translation initiation, is impacted by changes to the underlying genetic sequence, called start-site variants.

How are we doing it?

Using human cell-lines in the laboratory, we will add in start-site variants to carefully selected genes which cause monogenic disease. We will then assess the impact on translation initiation by measuring how much resultant protein is made, relative to the expected control level.

What happens next?

We will be able to better predict which genes are able to tolerate start-site variants and which are not, which is important for diagnostic variant classification. The outputs of this project will be used to inform further research to inform diagnostic interpretation of other predicted loss-of-function variants linked with disease.

Funding

NIHR Exeter BRC / PARADIGM Wellcome Discovery award.

People Involved

Prof. Caroline Wright, Prof. Ben Housden, Dr. Megan Stevens.