Drs. Doug Fowler (left) and Lea Starita: 'Genomic information will continue to influence healthcare decisions that will build healthier futures for all people regardless of race, gender, or ethnicity.'
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.
The two-year project will enable BBI to make significant progress toward creating a comprehensive Atlas of Variant Effects (AVE), benefitting clinicians and individuals carrying rare genetic variants, which often have unknown or poorly understood effects.
“Understanding how a person’s genetic variants affect their health and risk of disease is a critical step towards CZI’s mission to cure, prevent, or manage all diseases by the end of the 21st Century,” said BBI’s Lea Starita, Ph.D., who with BBI’s Doug Fowler, Ph.D., is leading the project. “Working directly with patient organizations within the Rare-As-One Network is a unique opportunity.”
By revealing how disease-associated genetic variants perturb molecular and cellular function, the AVE will advance precision medicine and help enable research and development of new, individualized treatments. Moreover, variant effect data is necessary to build AI systems to predict whether and how genetic variants alter cell and human biology.
“At the Chan Zuckerberg Initiative, we are committed to bridging the gap between patient communities, scientists and clinicians to address some of the most complex and challenging questions in rare disease research,” said Garabet Yeretssian, Ph.D., Senior Program Manager, Cell Science at CZI. “Our partnership with the Brotman Baty Institute represents a significant step forward in systematically advancing functional characterization of genetic variants, unlocking critical insights into disease mechanisms, and paving the way for precision diagnostics and treatments that can improve outcomes for people living with rare disease.”
Fowler noted that “the powerful partnership between CZI and BBI combines BBI’s leadership in the development, scaling, and clinical translation of variant effects with the unique resources, focus, and networks of the CZI.”
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.
“This project with CZI and patient organizations within the Rare as One Project has the potential to be groundbreaking,” said Fowler. “Understanding which variants lead to an increased risk of disease is imperative to the practice of precision medicine. Increasingly, genomic information will continue to influence healthcare decisions that will build healthier futures for all people regardless of race, gender, or ethnicity.”
