Federal Grant Award Summary

The University of Washington received a $698,290 Project Grant from the National Institute of Child Health and Human Development under the Child Health and Human Development Extramural Research program (CFDA 93.865) to conduct functional studies of non-coding DNA variants associated with orofacial cleft risk. The award, which commenced June 1, 2026, and concludes February 28, 2031, focuses on identifying and characterizing the pathogenic mechanisms underlying orofacial cleft (OFC), a relatively common structural birth defect with both environmental and genetic contributions.

The research deliverables include three integrated aims: (1) statistical identification of de novo non-coding mutations likely to be functional; (2) functional characterization of orofacial cleft-associated single nucleotide polymorphisms (SNPs) through in vitro reporter assays and induced pluripotent stem cell-based models engineered to express specific alleles and differentiated into embryonic oral epithelium; and (3) generation of genetically engineered mouse strains homozygous for proven functional risk or non-risk alleles to assess penetrance and expressivity of cleft phenotypes. The expected outcome is identification of the molecular mechanisms by which genetic risk variants cause this common birth defect, advancing understanding of disease etiology and potentially informing prevention and intervention strategies.