From Genetic Variant Identification to Improved Diagnosis of Rare Diseases.
Variants of uncertain significance (VUS) identified through genomic sequencing are evaluated using bioluminescence assays to determine their functional impact. These data help improve variant classification and rare disease diagnosis.

Rare genetic diseases affect many children, yet numerous patients remain undiagnosed despite advances in genomic sequencing. A major challenge lies in interpreting variants of uncertain significance (VUS), as their effects on gene and protein function often remain unknown.

This project aims to develop a medium-throughput experimental platform to rapidly assess the biological consequences of variants identified in patients receiving care through the pediatric genomic medicine program at CHU Sainte-Justine. Using bioluminescence-based approaches—which enable the rapid, quantitative acquisition of functional data—we are investigating how these variants impact various cellular mechanisms, including RNA splicing, gene expression, protein stability, and molecular interactions.

The data generated will help better distinguish pathogenic variants from benign ones, thereby facilitating more accurate interpretation of genetic results and improving the molecular diagnosis of rare diseases. By directly linking variant identification to an understanding of their biological consequences, this project adopts a translational approach aimed at improving the management of patients with rare diseases. In the longer term, this platform could also facilitate the identification of new therapeutic targets and support the development of precision medicine strategies.

Name: Dao, Wendenmi Tiziana Manuella
Supervisor: Dr. Philippe Campeau
Recipient: 2026 Doctoral Scholarship (scholarship declined)