Next-generation RNA genotype-phenotype mapping

The first human genome sequence was published in 2000 and thousands of genomes have been analysed since that time. We need to be able to predict the effects of mutations on molecules to fully use the information contained in these genomes, cells and organisms. To make these predictions, we first need to measure the effects of many mutations on each outcome.

We will develop methods that can be used to study the effects of thousands of mutations in parallel. We will apply these methods to study the mutations in a model yeast gene and try to understand how the different effects of mutations are related to each other – for example, whether we can predict the effects of mutations on yeast growth from their effects on molecular interactions of the model gene. We will then study a class of mutations that were long thought to have no effect in humans – the so-called ‘synonymous mutations’.

We have already shown that synonymous mutations influence gene expression and we will use our data to uncover the mechanisms underlying these effects.