A non-syndromic orofacial cleft risk locus links tRNA splicing defects to neural crest cell pathologies.

ABSTRACT: Orofacial clefts are the most common form of congenital craniofacial malformation worldwide. The etiology of these birth defects is multifactorial, involving genetic and environmental factors. However, in most cases, the underlying causes remain unexplained, precluding a molecular understanding of disease mechanisms. Here, we integrated genome-wide association data, targeted resequencing of case and control cohorts, tissue- and cell-type-specific epigenomic profiling, and genome architecture analyses to molecularly dissect a genomic locus associated with an increased risk of non-syndromic orofacial cleft. We found that common and rare risk variants associated with orofacial cleft intersect with an enhancer (e2p24.2) that is active in human embryonic craniofacial tissue. We mapped e2p24.2 l

SUBMITTER: Bartusel M 

PROVIDER: S-EPMC12120183 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature