Identifying suppressor mutations of ATR-X and ADNP syndromes using a novel CRISPR-based screening method in mice


  • Dr Rebekah Tillotson

    University of Oxford

Project summary

Every cell in our bodies contains the same set of instructions in our DNA. Yet, in different cell types, different genes must be expressed at different levels controlled by ‘epigenetic’ proteins. Mutations in genes encoding epigenetic proteins have been found to be a frequent cause of intellectual disability. However, establishing a genetic diagnosis is only the first step towards a cure. The severity of the effect of the same disease-causing mutations is variable, potentially due to other mutations.

Inspired by the idea that two wrongs could make a right in genetics, I designed a screening method to find genes that reduce the severity of genetic diseases. I will test this method using mouse models of two disorders: alpha thalassemia X-linked intellectual disability (ATR-X) syndrome and activity dependent neuroprotective protein (ADNP) syndrome.

My findings will help us understand why patients develop neurological abnormalities and identify pathways that could be targeted with drugs to ameliorate symptoms.