Clarifying Genomic Variants of Uncertain Significance and Supporting Personalized Medicine

The Initiative on Rare and Undiagnosed Diseases (IRUD), driven by AMED (Japan Agency for Medical Research and Developmtne), leverages genomic medicine to diagnose patients with rare and previously undiagnosed diseases. This approach has been made possible by recent rapid advancements in genetic analysis technology, yet it introduces new challenges. A primary challenge is the rise in Variants of Uncertain Significance (VUS) – genetic mutations with unclear roles in disease processes. Clarifying the pathological significance of these VUS requires validation of their effects both in vitro and in vivo. However, such analyses, especially in mouse models, are often not time and cost-effective without definitive evidence of their impact. To overcome this bottleneck, we utilize fruit flies for their rapid and cost-effective genetic analysis capabilities, enabling us to efficiently identify the pathological effects of disease-causing gene mutations. In partnership with clinical researchers, we are committed to elucidating as many VUS as possible. While merely identifying the pathological relevance does not equate to curing the disease, understanding the underlying causes can significantly aid in formulating treatment strategies, thereby offering reassurance to patients who have previously faced uncertainty. We are deeply motivated to contribute to this area, as echoed by the insights we have gained from numerous medical professionals.