The rockefeller university

Event Details

Type

Center for Studies in Physics and Biology Seminars

Speaker(s)

Yufeng Shen, Ph.D., associate professor, Columbia University

Speaker bio(s)

Developmental disorders, including congenital anomalies and neurodevelopmental disorders (NDD), affect many newborns and children. They are major factors associated with mortality, mobility, and long-term health of children and surviving adults. Finding genetic causes is fundamentally important for improving health care of these individuals and advancing basic research in human developmental biology. Previous efforts, which largely focused on de novo variants and loss of function variants with large effect, discovered new risk genes and pathways and were able to identify genetic causes in about 20-40% of “complex” cases who have additional congenital anomalies or NDD. The same approach was much less successful for “isolated” cases who do not have additional anomalies or NDD. A major analytical gap in previous studies is about rare inherited variants, especially missense variants, due to uncertainty of their genetic consequence and overall low signal-to-noise ratio. We reason that a key to address this issue is to leverage the fact that early onset severe conditions are under strong negative selection, therefore, genetic causes with moderate to large effect are under discernable negative selection. In this talk, I will go through MisFit, a new machine method developed based on population genetics models for estimating selection coefficient of missense variants. I’ll then show new results in autism regarding rare inherited variants and implications for rare congenital anomalies.

Open to

Public

Phone

(212) 327-8636

Sponsor

Melanie Lee
(212) 327-8636
leem@rockefeller.edu