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Computational Approach Towards Detection Of Functional Pathogenic Mutations In Dlx-1 Gene And Its Possible Association With Tooth Morphogenesis.
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| Author:
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R.BHARATHI , A.S.SMILINE GIRIJA, A.PARAMASIVAM, J.VIJAYASHREE PRIYADARSHINI
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| Abstract:
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Tooth morphogenesis is regulated by complex interplay between the genetic components. Dlx-1 is a homeobox gene encoding a transcription factor with functions linked to the craniofacial, limb and bone development. The Dlx-1 gene plays a vital role in the initiation of the tooth development process. The rationale of the present study was to elucidate the functional role of Dlx-1 mutations in the development of teeth using the in silico tools. In this study, the list of missense mutations in the Dlx-1 gene was retrieved from Ensembl database. Further, the deleterious effect of missense mutations was assessed using a variety of prediction tools such as SIFT, PolyPhen-2 and PROVEAN. Protein stability analysis and pathogenicity of the predicted variants was carried out using the I-Mutant Suite and MutPred tool respectively. The transcript of Dlx-1 gene analyzed was found to harbour 130 missense mutations. Among these mutations, 12 missense mutations were identified as damaging as assessed by three tools, viz., SIFT, PolyPhen and PROVEAN. Out of 12 damaging variants, 10 were found to decrease the stability of the protein, whereas 2 were found to increase the stability. Further, four variants with decreased stability were categorized as highly pathogenic (>0.800) depending on the MutPred Score. The association between these variants and their role in tooth development was verified using a text-mining process. Pathogenic mutations identified in the Dlx-1 gene provide a novel insight into the genotyping approach which could provide substantial information about the crucial mutations and their association with the developmental process. The mutations identified in the present study should be validated using population based experiments so as to derive an association between the Dlx-1 mutations and disorders related to tooth morphogenesis.
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| Keyword:
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Dlx-1 gene, tooth morphogenesis, single nucleotide polymorphism, pathogenic mutations, homeobox gene, patterning.
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2020.12.04.454
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| Download:
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