Gene Expression Profiles of the Cochlea and Vestibular Endorgans

Abstract

Objectives: We sought to elucidate the gene expression profiles of the causative genes as well as the localization of the encoded proteins involved in hereditary hearing loss. Methods: Relevant articles (as of September 2014) were searched in PubMed databases, and the gene symbols of the genes reported to be associated with deafness were located on the Hereditary Hearing Loss Homepage using localization, expression, and distribution as keywords. Results: Our review of the literature allowed us to systematize the gene expression profiles for genetic deafness in the inner ear, clarifying the unique functions and specific expression patterns of these genes in the cochlea and vestibular endorgans. Conclusions:The coordinated actions of various encoded molecules are essential for the normal development and maintenance of auditory and vestibular function.

RefEx, a reference gene expression dataset as a web tool for the functional analysis of genes

“…The gene expression profile of noncardiac MRLC (myosin, light chain 12A, NM_006471) in RefEx was used to confirm the conclusions because noncardiac MRLC was expressed in the heart at the same level as that in the skeletal muscle while it was annotated as ‘non-cardiac’ 25 . Furthermore, in a review article, RefEx was used to list the gene expression profiles of all genes previously reported to cause deafness 26 . The data retrieved from RefEx strengthened the authors’ hypotheses without the need for further wet-lab experiments in all cases.…”

Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance

“…Damaging variants (those with phred-like CADD score > 10, predicted to be among the top 10% most likely damaging variants possible in the human genome) were examined. CADD scores were extracted for genes implicated in auditory neuropathy (not synaptopathy) or with an expression pattern and previously reported function in the spiral ganglion (Moser and Starr 2016; Nishio et al, 2015). The complete list of these neural genes is as follows: OPA1, DIAPH3, DFNB59, AIFM1, TBC1D24, MT-RNR1, and TMPRSS3 (Figure 1).…”

Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis

“…Other such genes included Cldn14, Tmprss3, Pcdh15 and Gjb2 (Table S4, sheet 1). To determine whether additional such genes, or those responsible for mouse hearing loss and/or cochlear development, were enriched in either the up-or downregulated genes, we conducted a gene set enrichment analysis (Subramanian et al, 2005) on all 16,232 genes detected in the Seq1 paired analysis using two partially overlapping gene lists: 95 human hereditary hearing loss genes identified by Nishio et al (2015; rank listed in Table S4, sheet 3) and 258 mouse genes involved in inner ear development or function collated by Ohlemiller et al (2016;rank listed in Table S4, sheet 4). Both gene sets were highly enriched in the upregulated Seq1 dataset (normalized enrichment score=2.09 for the human genes and 2.06 for the mouse genes; both nominal P-values <1×10 −3 ), but not in the downregulated set.…”

“…To identify significantly regulated pathways (P<0.05, Fisher's Exact Test), all differentially expressed genes were loaded into Ingenuity Pathway Analysis (Qiagen, https://www.qiagenbioinformatics.com/ products/ingenuity-pathway-analysis/). For gene set enrichment analysis (GSEA), two custom gene sets based on human hearing loss genes from Nishio et al (2015) and mouse inner ear genes from Ohlemiller et al (2016) were loaded into the Broad Institute GSEA website (Subramanian et al, 2005) and compared with ranked lists of otocyst genes sorted by fold-change from DESeq2.…”