Avraham Karen B, Khalaily Lama, Noy Yael, Kamal Lara, Koffler-Brill Tal, Taiber Shahar
Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel.
Hum Genet. 2022 Apr;141(3-4):323-333. doi: 10.1007/s00439-021-02359-z. Epub 2021 Sep 7.
The age of sequencing has provided unprecedented insights into the human genome. The coding region of the genome comprises nearly 20,000 genes, of which approximately 4000 are associated with human disease. Beyond the protein-coding genome, which accounts for only 3% of the genome, lies a vast pool of regulatory elements in the form of promoters, enhancers, RNA species, and other intricate elements. These features undoubtably influence human health and disease, and as a result, a great deal of effort is currently being invested in deciphering their identity and mechanism. While a paucity of material has caused a lag in identifying these elements in the inner ear, the emergence of technologies for dealing with a minimal number of cells now has the field working overtime to catch up. Studies on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), methylation, histone modifications, and more are ongoing. A number of microRNAs and other noncoding elements are known to be associated with hearing impairment and there is promise that regulatory elements will serve as future tools and targets of therapeutics and diagnostics. This review covers the current state of the field and considers future directions for the noncoding genome and implications for hearing loss.
测序时代为人类基因组带来了前所未有的见解。基因组的编码区域包含近20000个基因,其中约4000个与人类疾病相关。在仅占基因组3%的蛋白质编码基因组之外,存在着大量以启动子、增强子、RNA种类及其他复杂元件形式存在的调控元件。这些特征无疑会影响人类健康和疾病,因此,目前人们投入了大量精力来破译它们的身份和机制。尽管内耳中材料的匮乏导致在识别这些元件方面有所滞后,但现在能够处理极少量细胞的技术的出现,使得该领域正在加班加点地追赶。关于微小RNA(miRNA)、长链非编码RNA(lncRNA)、甲基化、组蛋白修饰等的研究正在进行。已知一些微小RNA和其他非编码元件与听力障碍有关,并且有望作为未来治疗和诊断的工具及靶点。本综述涵盖了该领域的当前状况,并探讨了非编码基因组的未来方向以及对听力损失的影响。