Format

Send to

Choose Destination
Oral Dis. 2017 Oct;23(7):966-972. doi: 10.1111/odi.12680. Epub 2017 May 16.

Genetic alterations in mesiodens as revealed by targeted next-generation sequencing and gene co-occurrence network analysis.

Author information

1
Institute of Oral Science, Apple Tree Dental Hospital, Ilsansuh-gu, Goyang, Korea.
2
Department of IT Convergence and Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
3
Department of Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
4
Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine, Dongdaemoon-gu, Seoul, Korea.
5
Department of Prosthodontics, Yonsei University College of Dentistry, Seodaemoon-gu, Seoul, Korea.

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. A total of 101 candidate genes which were captured custom genes were sequenced on the Illumina HiSeq 2500. 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.

KEYWORDS:

bone morphogenetic proteins (BMP); gene co-occurrence network analysis; mesiodens; sonic hedgehog (SHH); targeted next generation sequencing; wingless integrated (WNT)

PMID:
28415132
DOI:
10.1111/odi.12680
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center