Disease-associated variants at ARID5B

While the impact of mutations at genes can be directly predicted, sequence variants at non-genic part of our genome are much more difficult to identify and to understand. Yet, large genetic studies in the human population identified several mutations in the intergenic space, that are associated with disease. In this project, we focus on intergenic mutations at ARID5B, that are associated with high risk of developing childhood leukemia. Our hypothesis is that intergenic mutations result in reduction in the levels of ARID5B in the blood, and that low ARID5B levels make blood more vulnerable to leukemia. We will use genetic engineering tool to reproduce in the lab those mutations observed in patients. Next, we will use biochemical approaches to study how the protein ARID5B contributes to the development of leukemia. Finally, we will use mouse models lacking the gene ARID5B and observe how blood develops in the absence of that gene. These experiments will allow us to understand better how normal blood and leukemia develops and how mutations away from genes can affect these processes.