RNA-Seq and microarray analysis of the Xenopus inner ear transcriptome discloses orthologous OMIM® genes for hereditary disorders of hearing and balance

Abstract

BackgroundAuditory and vestibular disorders are prevalent sensory disabilities caused by genetic and environmental (noise, trauma, chemicals) factors that often damage mechanosensory hair cells of the inner ear. Development of treatments for inner ear disorders of hearing and balance relies on the use of animal models such as fish, amphibians, reptiles, birds, and non-human mammals. Here, we aimed to augment the utility of the genus Xenopus for uncovering genetic mechanisms essential for the maintenance of inner ear structure and function.ResultsUsing Affymetrix GeneChip®X. laevis Genome 2.0 Arrays and Illumina-Solexa sequencing methods, we determined that the transcriptional profile of the Xenopuslaevis inner ear comprises hundreds of genes that are orthologous to OMIM® genes implicated in deafness and vestibular disorders in humans. Analysis of genes that mapped to both technologies demonstrated that, with our methods, a combination of microarray and RNA-Seq detected expression of more genes than either platform alone.ConclusionsAs part of this study we identified candidate scaffold regions of the Xenopus tropicalis genome that can be used to investigate hearing and balance using genetic and informatics procedures that are available through the National Xenopus Resource (NXR), and the open access data repository, Xenbase. The results and approaches presented here expand the viability of Xenopus as an animal model for inner ear research.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1485-1) contains supplementary material, which is available to authorized users.

Using Xenopus to understand human disease and developmental disorders

“…The use of Xenopus eggs and embryos for in vivo analyses of disease gene expression and function has exploded in recent years. This model has supported important advances in our understanding of: neurological disorders including autism, Alzheimer's disease, and depression (James et al, ; Park et al, ; Ramirez‐Vizcarrando, Hasan, Gu, Khakhalin, & Aizenman, ; Ullah, Demuro, Parker, & Pearson, ); cancers (Green, Kwon, & Christian, ; Haynes‐Gilmore et al, ; Van Nieuwenhuysen et al, ; Wei et al, ); congenital heart defects (Endicott, Basu, Khokha, & Brueckner, ; Silva et al, ; Torres‐Prioris, Smith, Mohun, Fernández, & Durán, ); craniofacial and auditory malformations (Dickinson, ; Griffin, Sondalle, Del Viso, Baserga, & Khokha, ; Moody, Neilson, Kenyon, Alfandari, & Pignoni, ; Ramírez‐Gordillo et al, ); diabetes (Kofent & Spagnoli, ; Pearl, Jarikji, & Horb, ; Salanga & Horb, ); kidney disease (Desgrange & Cereghini, ; Lienkamp, ; Stiburkova, Stekrova, Nakamura, & Ichida, ); Lennox–Gastaut syndrome (Hammer, Ebert, Jensen, & Jensen, ); and Zimmermann–Laband syndrome (Kortüm et al, ).…”

Time-resolved quantitative proteomic analysis of the developing Xenopus otic vesicle reveals putative congenital hearing loss candidates

“…To assess the depth of coverage, we compared our Xenopus dataset to previously published transcriptomic data from Xenopus inner ears as well as proteomic data from dissected postnatal mouse inner ear tissues. 4 , 18 From our dataset of ∼6000 proteins, 178 proteins were previously shown to be present in inner ear tissues (n = 164) and hair cells (n = 14) ( Figure 2 A), including proteins that play important roles in proper functioning of the inner ear such as alpha-tectorin (Tecta), a protein present in the tectorial membrane that connects the stereocilia bundles of hair cells ( Table S1 ). We also compared our Xenopus dataset to known human deafness genes reported on OMIM and matched >70 proteins to genes that are associated with syndromic CHL such as SIX1 (associated with BOR syndrome, OMIM entry 601205) and CHD7 (associated with CHARGE syndrome, OMIM entry 608892).…”

Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome, and Transcriptome in Health and Disease

“…Previous studies on the auditory transcriptome were performed using microarray technologies and bulk RNA-seq [116], providing significant knowledge and information on the differential gene expression in physiological and pathological conditions of the cochlea, with important implications for the development of new therapies [117,118]. Studies on the transcriptome have also given insights into the developmental processes of the inner ear [119], the transcriptional changes associated with ageing [120], and cochlear cell damage/degeneration [121].…”