In Silico Analyses of Mouse Inner-Ear Transcripts

Abstract

The development and function of the inner ear is complex requiring the correct and coordinated expression of many genes. The recent progress in the analyses of the human and other genomes has provided tools for identification of genes involved in hearing. As more and more nucleotide sequence information accumulates, experimental methods of molecular biology are rapidly being supplemented, and partially supplanted, by computational methods. In this study we present comprehensive in silico analyses of a cDNA library representing almost 1600 transcripts isolated from mouse inner ear. By mining the public databases we were able to rapidly and efficiently identify numerous transcripts likely to have a specific role in the auditory or vestibular function of the inner ear. Analyses revealed about 600 known genes and almost 100 inner-ear specific transcripts. Almost 50 of these are candidate genes for hearing impairment based on their chromosomal localization and inner-ear expression pattern. We describe a powerful approach to identify novel genes associated with hearing and vestibular function, further increasing our understanding of the molecular biology of the inner ear.

Gene expression profiling analysis of the inner ear

“…Since the inner ear is composed of dozens of highly specialized cell types, a large amount of important data is lost when this type of approach is adopted, as the unique characteristics of individual cell types do not form part of the analysis. For example, in the study by Klockars et al (2003), oncomodulin and prestin were not identified as inner ear transcripts, yet they are reported to be expressed selectively in outer hair cells (Zheng et al, 2000(Zheng et al, , 2002. A likely explanation for this result is that despite the high expression of the prestin and oncomodulin transcripts in outer hair cells, their overall expression in the mixture of inner ear cells is relatively low.…”

“…The Soares NMIE library was derived from the pooled inner ear tissue of 170 mice (http://image.llnl.gov/ image/bin/libinfo; Table 1(4)). Of the 1536 clones in the library, 147 displayed preferential in silico expression in the inner ear and only 13 of these clones represented known genes (Klockars et al, 2003). Interestingly, 91 of the 147 clones appeared to be inner ear specific, representing only approximately 6% of the clones in this library (Klockars et al, 2003).…”

“…Whilst a number of genes preferentially expressed in the inner ear have been shown to be important for auditory or vestibular function, it now appears that only a relatively small proportion of transcripts are specifically expressed in the inner ear Klockars et al, 2003). A comprehensive in silico analysis of the Soares NMIE cDNA library by Klockars et al (2003) identified transcripts with potential roles in auditory and vestibular function.…”

“…The screening of cDNA libraries is increasingly being used to identify genes involved in inner ear function (Table 1) (Asamura et al, 2005;Beisel et al, 2004;Chen and Corey, 2002a;Crozet et al, 1997;Hildebrand et al, 2004Hildebrand et al, , 2005aKlockars et al, 2003;Luijendijk et al, 2003;Morris et al, 2005;Robertson et al, 1994Robertson et al, , 1998. These studies have generally focused on identifying genes that are preferentially expressed in the inner ear relative to their expression in other tissues.…”

“…A comprehensive in silico analysis of the Soares NMIE cDNA library by Klockars et al (2003) identified transcripts with potential roles in auditory and vestibular function. The Soares NMIE library was derived from the pooled inner ear tissue of 170 mice (http://image.llnl.gov/ image/bin/libinfo; Table 1(4)).…”