Gabashvili Irene S, Sokolowski Bernd H A, Morton Cynthia C, Giersch Anne B S
Hewlett-Packard Labs, 1501 Page Mill Road, Palo Alto, CA 94304, USA.
J Assoc Res Otolaryngol. 2007 Sep;8(3):305-28. doi: 10.1007/s10162-007-0082-y. Epub 2007 Jun 1.
The ion channel genome is still being defined despite numerous publications on the subject. The ion channel transcriptome is even more difficult to assess. Using high-throughput computational tools, we surveyed all available inner ear cDNA libraries to identify genes coding for ion channels. We mapped over 100,000 expressed sequence tags (ESTs) derived from human cochlea, mouse organ of Corti, mouse and zebrafish inner ear, and rat vestibular end organs to Homo sapiens, Mus musculus, Danio rerio, and Rattus norvegicus genomes. A survey of EST data alone reveals that at least a third of the ion channel genome is expressed in the inner ear, with highest expression occurring in hair cell-enriched mouse organ of Corti and rat vestibule. Our data and comparisons with other experimental techniques that measure gene expression show that every method has its limitations and does not per se provide a complete coverage of the inner ear ion channelome. In addition, the data show that most genes produce alternative transcripts with the same spectrum across multiple organisms, no ion channel gene variants are unique to the inner ear, and many splice variants have yet to be annotated. Our high-throughput approach offers a qualitative computational and experimental analysis of ion channel genes in inner ear cDNA collections. A lack of data and incomplete gene annotations prevent both rigorous statistical analyses and comparisons of entire ion channelomes derived from different tissues and organisms.
尽管已有大量关于离子通道基因组的文献发表,但离子通道基因组仍有待明确。离子通道转录组的评估则更加困难。我们使用高通量计算工具,对所有可用的内耳cDNA文库进行了调查,以鉴定编码离子通道的基因。我们将来自人类耳蜗、小鼠柯蒂氏器、小鼠和斑马鱼内耳以及大鼠前庭终器的超过100,000个表达序列标签(EST)定位到人类、小鼠、斑马鱼和大鼠的基因组上。仅对EST数据的调查就显示,至少三分之一的离子通道基因组在内耳中表达,在富含毛细胞的小鼠柯蒂氏器和大鼠前庭中表达最高。我们的数据以及与其他测量基因表达的实验技术的比较表明,每种方法都有其局限性,本身并不能完全覆盖内耳离子通道组。此外,数据显示大多数基因在多种生物体中产生具有相同谱型但不同的转录本,没有离子通道基因变体是内耳特有的,并且许多剪接变体尚未得到注释。我们的高通量方法对内耳cDNA文库中的离子通道基因进行了定性的计算和实验分析。数据的缺乏和基因注释的不完整阻碍了对来自不同组织和生物体的整个离子通道组进行严格的统计分析和比较。