Uncovering the Pathogenesis of Orofacial Clefts Using Bioinformatics Analysis.

ABSTRACT

OBJECTIVE: Many genes have been found to be associated with the occurrence of the orofacial clefts (OFC). The links between these pathogenic genes are rarely studied. In this study, bioinformatics analysis were performed in order to find associations between OFC- related genes and provide new ideas for etiology study of OFCs. METHODS: Orofacial clefts-related genes were searched and identified from the Online Mendelian Inheritance of Man (OMIM.org). These genes were then analyzed by bioinformatics methods, including protein-protein interaction network, functional enrichment analysis, module analysis, and hub genes analysis. RESULTS: After searching the database of OMIM.org and removing duplicate results, 279 genes were finally obtained. These genes were involved to 369 pathways in biological process, 56 in cell component, 64 in molecular function, and 45 in the Kyoto Encyclopedia of Genes and Genomes. Most identified genes were significantly enriched in embryonic appendage morphogenesis (29.17%), embryonic limb morphogenesis (6.06%), and limb development (4.33%) for biological process ( Fig. 5A ); ciliary tip (42.86%), MKS complex (28.57%), ciliary basal body (14.29%), and ciliary membrane (14.29%) for cell component. The top 10 hub genes were identified, including SHH, GLI2, PTCH1, SMAD4, FGFR1, BMP4, SOX9, SOX2, RUNX2 , and CDH1. CONCLUSIONS: Bioinformatics methods were used to analyze OFC- related genes in this study, including hub gene identifying and analysis, protein - protein interaction network construction, and functional enrichment analysis. Several potential mechanisms related to occurrence of OFCs were also discussed. These results may be helpful for further studies of the etiology of OFC.