Reckoning the SIX1 mutation’s effects in branchio-oto-renal syndrome — A bioinformatics approach

B. Preethi, V. Shanthi, K. Ramanathan

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Front. Biol. ›› 2015, Vol. 10 ›› Issue (5) : 448-457. DOI: 10.1007/s11515-015-1370-2
RESEARCH ARTICLE
RESEARCH ARTICLE

Reckoning the SIX1 mutation’s effects in branchio-oto-renal syndrome — A bioinformatics approach

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Abstract

Branchio-oto-renal syndrome (BOR) is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstrating, missense mutations responsible in disease were located in SIX1, EYA1 and EYA2 genes. We try to uncover molecular biology of the syndrome with bioinformatics perspective, taking SIX1 and EYA2 protein interaction at center point. The study initiated with 23 natural mutations of SIX1 gene. They were first analyzed with prediction servers like SIFT, PolyPhen2, I Mutant, SNPs&GO, PHD-SNP and Panther, to identify their impact on their structural stability and function. Subsequently it narrowed down to seven consistent with our quest. They were analyzed on IUPred disorder prediction server. Later SIX1 and its all mutant proteins were docked with EYA2 protein using GRAMM-X server. The binding affinity of docked structures was analyzed using DFIRE2 algorithm. The results justify the earlier wet laboratory studies and indicate the reason behind them. Finally we summarize that the proven inactivity of all other mutants is due to the structural disorder created by mutations, hence usual molecular interaction is hindered; strangely protein interaction takes place at DNA binding site of SIX1 mutants.

Keywords

branchio-oto-renal syndrome (BOR) / hearing loss / damaging mutations / SIX1 / EYA2 / protein-protein interactions

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B. Preethi, V. Shanthi, K. Ramanathan. Reckoning the SIX1 mutation’s effects in branchio-oto-renal syndrome — A bioinformatics approach. Front. Biol., 2015, 10(5): 448‒457 https://doi.org/10.1007/s11515-015-1370-2

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Acknowledegment

The authors express a deep sense of gratitude to the management of Vellore Institute of Technology for all the support, assistance and constant encouragement to carry out this work.
Compliance with ethics guidelines
B. Preethi, V. Shanthi and K. Ramanathan declare that they do not have any conflicts of interest.This article does not contain any studies with human or animal subjects performed by any of the authors.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
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