The two main goals of this project are to use advanced genetic analysis to identify specific genetic variants within the PWS region that impact brain structure in typically developing children, and to investigate how the 3D structure of DNA within the PWS region affects the activity of these genes during brain development.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Prader-Willi Syndrome (PWS) results from the loss of specific genetic instructions on the chromosome region 15q11-q13, which is critical for normal brain development. While we broadly understand which genes are involved, we still do not fully comprehend how variations within this genetic region affect brain structure and function. This project aims to identify precisely how common genetic differences in the PWS region impact brain development and to determine the specific genes and regulatory elements involved.
Our research has two main goals:
First, we will use advanced genetic analysis to identify specific genetic variants within the PWS region linked to variations in brain structure in typically developing children. We will integrate these genetic findings with data on gene expression to determine which genes these variants might influence.
Second, we will investigate how the 3D structure of DNA within the PWS region affects the activity of these genes during brain development. This involves mapping the physical interactions between DNA segments that regulate gene activity, helping us understand how genetic variants might disrupt these interactions and influence gene function. This research is significant because it bridges the gap between genetic variants and their direct biological impacts, providing a clear understanding of how subtle genetic differences may influence brain development and contribute to features of PWS. The methods we are using are innovative, combining genetics, neuroimaging, and advanced DNA interaction mapping techniques to reveal new insights into the mechanisms underlying PWS.
If successful, this study will significantly impact both immediate and long-term PWS research and care. In the short term (within 2–5 years), it could identify specific genetic markers useful for earlier diagnosis or risk assessment. In the longer term (over 5 years), our findings could lead directly to targeted treatments aimed at correcting disrupted gene regulation, potentially improving developmental outcomes for individuals with PWS. Ultimately, by establishing a detailed understanding of genetic and regulatory mechanisms in the PWS region, our project lays critical groundwork for developing precise, personalized therapeutic strategies, significantly advancing clinical care for those living with PWS.