Project description:Oral facial cleft (OFC) is a multifactorial disorder that can present as a cleft lip with or without cleft palate (CL/P) or a cleft palate only. Genome wide association studies (GWAS) of isolated OFC have identified common single nucleotide polymorphisms (SNPs) at the 1q32/IRF6 locus and many other loci where, like IRF6, the gene presumed to be relevant to OFC risk is expressed in embryonic oral epithelium. To identify the functional subset of SNPs at eight such loci we conducted a massively parallel reporter assay in a cell line derived from fetal oral epithelium, revealing SNPs with allele-specific effects on enhancer activity.
Project description:Oral facial cleft (OFC) is a multifactorial disorder that can present as a cleft lip with or without cleft palate (CL/P) or a cleft palate only. Genome wide association studies (GWAS) of isolated OFC have identified common single nucleotide polymorphisms (SNPs) at the 1q32/IRF6 locus and many other loci where, like IRF6, the gene presumed to be relevant to OFC risk is expressed in embryonic oral epithelium. To identify the functional subset of SNPs at eight such loci we conducted a massively parallel reporter assay in a cell line derived from fetal oral epithelium, revealing SNPs with allele-specific effects on enhancer activity.
Project description:We sought to identify Hedgehog-regulated genes in the frontonasal process (FNP) and ventral prosencephalon at GD9.25 in mice, during the initial pathogenesis of cleft lip with or without cleft palate.
Project description:Genome-wide DNA methylation profilinf from 67 non syndromic cleft lip and palate samples and controls using whole-blood DNA and Illumina Infinium Human Methylation 450K Bead array, in which over 485000 CpGs sites were analysed per sample
Project description:ARHGAP29 is implicated in nonsyndromic cleft lip with or without cleft palate, but its role in human palatal mesenchymal cells remains incompletely understood. Human embryonic palatal mesenchymal (HEPM) cells were transfected with ARHGAP29-targeting siRNA or a non-targeting negative-control siRNA. Total RNA sequencing was performed for three independent biological replicates per group. The study was designed to identify transcriptional changes associated with ARHGAP29 depletion. Differential expression and functional enrichment analyses indicated changes in developmental and stress-responsive gene programs, including p53- and Notch-related pathways.
