Mit Biologists Discover Genetic Link to Cleft Lip and Palate Development

MIT biologists have discovered a genetic variant linked to cleft lip and palate development. The study, published in *The American Journal of Human Genetics*, reveals how this variant disrupts transfer RNA (tRNA) production. This disruption impairs protein synthesis in embryonic face cells, preventing proper fusion and leading to malformations. The research team, led by Michaela Bartusel and Eliezer Calo, found that the genetic variant affects the *DDX1* gene. *DDX1* is crucial for splicing tRNA molecules, which transport amino acids needed for protein synthesis. Without functional *DDX1*, certain tRNAs can't deliver amino acids, stalling ribosomes and hindering protein production. Genome-wide association studies (GWAS) previously identified genetic variants in a non-coding DNA region associated with orofacial clefts. The MIT team found these variants in an enhancer region called e2p24.2, near the *DDX1* gene. Further research will explore which proteins are most affected by tRNA loss and the impact of ribosome stalling on cells. Previous studies have linked ribosome formation and tRNA synthesis disruptions to similar developmental issues. Researchers will also investigate how environmental factors, like oxidative stress from ethanol exposure or gestational diabetes, impact tRNA function. This could lead to preventative measures for orofacial clefts.