Identification of functional non-coding variants associated with orofacial cleft.

ABSTRACT: Oral facial cleft (OFC) comprises cleft lip with or without cleft palate (CL/P) or cleft palate only. Genome wide association studies (GWAS) of isolated OFC have identified common single nucleotide polymorphisms (SNPs) in many genomic loci where the presumed effector gene (for example, IRF6 in the 1q32 locus) is expressed in embryonic oral epithelium. To identify candidates for functional SNPs at eight such loci we conduct a massively parallel reporter assay in a fetal oral epithelial cell line, revealing SNPs with allele-specific effects on enhancer activity. We filter these SNPs against chromatin-mark evidence of enhancers and test a subset in traditional reporter assays, which support the candidacy of SNPs at loci containing FOXE1, IRF6,  MAFB, TFAP2A, and TP63. For two SNPs near IRF6 a

SUBMITTER: Kumari P 

PROVIDER: S-EPMC12267437 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature