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探究非洲爪蟾内耳转录组的生物学功能。

Probing the Xenopus laevis inner ear transcriptome for biological function.

机构信息

Biology Department, New Mexico State University, Las Cruces, USA.

出版信息

BMC Genomics. 2012 Jun 8;13:225. doi: 10.1186/1471-2164-13-225.

Abstract

BACKGROUND

The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.

RESULTS

Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip(®) Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization.

CONCLUSIONS

We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the impediment imposed by insufficient gene annotation. These findings heighten the relevance of Xenopus as a model organism for genetic investigations of inner ear organogenesis, morphogenesis, and regeneration.

摘要

背景

听觉和平衡感依赖于机械感受,这一过程始于内耳,且在各物种间具有相似特征。两栖动物被广泛用于研究感觉毛细胞的机械转导的生理学。相比之下,人们对内耳听觉和前庭功能在这一类动物中的遗传基础了解甚少。在两栖动物中,非洲爪蟾是一种具有良好特征的遗传和发育模型,由于其具有组织和器官再生的能力,为内耳研究提供了独特的机会。基于这些原因,我们采用功能基因组学方法,通过微阵列分析对内耳转录组进行大规模分析。

结果

微阵列分析揭示了与内耳功能相关的基因,以及与其他生物体内耳功能障碍相关的基因,从而支持将非洲爪蟾纳入内耳跨物种遗传研究。使用基因类别(内耳组织;耳聋;离子通道;离子转运蛋白;转录因子)有助于确定探针集标识符的功能意义。我们通过使用各种策展方法来增强我们的微阵列数据的生物学相关性,从而增加了 Affymetrix GeneChip®非洲爪蟾基因组阵列的注释。此外,注释分析显示,代表缺乏功能特征的探针集标识符的内耳转录本的普遍性。

结论

我们确定了大量的听觉和前庭功能遗传分析的靶标。具有已知内耳功能的人类基因的同源物和缺乏注释的高度表达的转录本是未来分析特别有趣的候选物。我们使用信息学方法为非洲爪蟾内耳转录组赋予生物学相关信息,从而解决了基因注释不足的障碍。这些发现提高了非洲爪蟾作为内耳器官发生、形态发生和再生遗传研究模型的相关性。

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