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

Authors
 Y Y Kim  ;  J Hwang  ;  H‐S Kim  ;  H J Kwon  ;  S Kim  ;  J H Lee  ;  J H Lee 
Citation
 Oral Diseases, Vol.23(7) : 966-972, 2017 
Journal Title
 Oral Diseases 
ISSN
 1354-523X 
Issue Date
2017
MeSH
Computational Biology ; DNA Mutational Analysis ; High-Throughput Nucleotide Sequencing* ; Humans ; Mutation ; Tooth, Supernumerary/diagnostic imaging ; Tooth, Supernumerary/genetics*
Keywords
bone morphogenetic proteins (BMP) ; gene co-occurrence network analysis ; mesiodens ; sonic hedgehog (SHH) ; targeted next generation sequencing ; wingless integrated (WNT)
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.
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1111/odi.12680
DOI
10.1111/odi.12680
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Prosthodontics (보철과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jae Hoon(이재훈) ORCID logo https://orcid.org/0000-0003-2281-8885
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161732
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