Genetic alterations in mesiodens as revealed by targeted NGS and gene co-occurrence network analysis

Abstract

Objective

Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next generation sequencing and bioinformatics are cost-effective for large samples and target sizes.

Materials and Methods

We describe the application of a targeted next generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients. Subjects were diagnosed on the basis of panoramic radiograph. 101 candidate genes which were captured custom gene were sequenced on the Illumina HiSeq2500. Multistep bioinformatics processing was performed including variant identification, base calling, and in silico analysis of putative disease-causing variants.

Results

Targeted capture identified 88 non-synonymous, rare, exonic variants involving 42 of the 101 candidate genes. Moreover, we investigated gene co-occurrence relationships between the genomic alterations and identified 88 significant relationships among 18 most recurrent driver alterations.

Conclusion

Our search for co-occurring genetic alterations revealed that such alterations interact cooperatively to drive mesiodens. We discovered a gene co-occurrence network in mesiodens patients with functionally enriched gene groups in the sonic hedgehog (SHH), bone morphogenetic proteins (BMP), and wingless integrated (WNT) signaling pathways.

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