Rare Variant Exploration Hub
Critical step toward CZI’s mission to cure, prevent, or manage diseases by end of 21st Century
The Chan Zuckerberg Initiative (CZI) has awarded the Brotman Baty Institute $4.5 million to advance its work on genetic variants, including partnering with patient organizations within CZI’s “Rare As One” Project.
BBI researchers have developed and implemented technologies to generate a large volume of variant effect data that will immediately benefit rare disease patient communities. They optimize and scale three assays: Saturation Genome Editing, Variant Abundance by Massively Parallel Sequencing, and Multiplexed Surface Tethering for Extracellular Proteins. These assays have been used to measure the effects of every possible single nucleotide variant in several genes. The funding is also earmarked for development of new technologies.
The resulting variant effect data can transform the diagnosis of rare diseases, empowering clinicians to accurately identify individuals with the disease, discover patients with atypical or moderate phenotypes, and chart courses of treatment. Moreover, such data can reveal the mechanism by which each variant acts on the molecular and cellular level, thereby opening new doors for therapeutic development.
Goals
Our goal is to generate variant effect data in support of the rare disease community. Specifically, we aim to:
- Identify and grow partnerships with rare-disease organizations, clinicians and researchers interested in having comprehensive variant effect data
- Generate comprehensive variant effect data for genes associated with these diseases
- Use the variant effect data we generate to reinterpret variants of uncertain significance as either pathogenic or benign
- Combine the variant effect data with natural history and biometric data to understand how molecular and cellular defects caused by genetic variants alter patient outcomes
- Collaborate with experts in the disease-associated genes to understand the mechanisms by which genetic variants cause disease
- Collaborate with therapeutic developers to guide the development of antisense oligonucleotides (ASOs) or gene/protein therapies