Black, Joshua CranstonSullivan, Kelly D
Summary
This project will test the transformative hypothesis that dysregulated DNA rereplication in response to cellular stress contributes to the development of Trisomy 21 (T21) and subsequent pathophysiology of Down syndrome (DS). This project arises from the observation the interferon receptor cluster encoded on chromosome 21 undergoes DNA rereplication and targeted transient site-specific gene amplification in response to viral infection in healthy cells; however, this process is impaired in T21 cells. To test our hypothesis, we will employ a combination of human and mouse culture models and a mouse in vitro fertilization model to define the extent of DNA rereplication dysregulation in T21 and how DNA rereplication could contribute to the development of T21 and comorbidities associated with DS.