Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish.

Fei Liu,Jiongjiong Hu,Shaoyang Sun,Jin Zhang,Yingzhi Wang,Huijun Wang,Nan Jiang,Duan Ma,Xu Wang,Wenjun Xia,Fan Yang,Weidong Tian,Berta Alsina

doi:10.1371/journal.pone.0136832

Fei Liu, Jiongjiong Hu + Show 11 more

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https://doi.org/10.1371/journal.pone.0136832

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Abstract

Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by-association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL) genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO), and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment.

Highlights

Hearing impairment is one of the most common losses of meaningful function in humans, and it poses a persistent threat to worldwide public health
77 reported deafness genes were classified according to their biological characteristics, and the categorization system was combined with 2,455 gene ontology (GO) terms
More than 300 deafness candidate genes were predicted according to the features of 16 gene types and 6 class interaction relationships among different genes based on analysis and simulations using the Funckenstein algorithm

Summary

Introduction

Hearing impairment is one of the most common losses of meaningful function in humans, and it poses a persistent threat to worldwide public health. 10% of people worldwide have mild or moderate hearing impairment [1]. Genetic factors are important to the pathogenesis of deafness, and 80% of genetic deafness is non-syndromic hearing impairment (NSHI). Most deafness-causing genes have been identified in inherited deafness pedigrees by linkage analysis, but similar pedigrees have been difficult to find in modern society.

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