Laboratório de Otorrinolaringologia/LIM 32, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil.
Otorhinolaryngology Department, Faculdade de Medicina da Universidade de São Paulo, São Paulo 05508-060, Brazil.
Genes (Basel). 2022 Dec 2;13(12):2274. doi: 10.3390/genes13122274.
Hearing loss is the most common sensory deficit, affecting 466 million people worldwide. The vast and diverse genes involved reflect the complexity of auditory physiology, which requires the use of animal models in order to gain a fuller understanding. Among the loci with a yet-to-be validated gene is the DFNA58, in which ~200 Kb genomic duplication, including three protein-coding genes (, , and 's exon1), was found to segregate with autosomal dominant hearing loss. Through whole genome sequencing, the duplication was found to be in tandem and inserted in an intergenic region, without the disruption of the topological domains. Reanalysis of transcriptomes data studies (zebrafish and mouse), and RT-qPCR analysis of adult zebrafish target organs, in order to access their orthologues expression, highlighted promising results with corroborated by zebrafish in situ hybridization and immunofluorescence. Mouse data also suggested as the best candidate for a relevant role in auditory physiology, and its importance in hearing seems to have remained conserved but the cell type exerting its function might have changed, from hair cells to spiral ganglion neurons.
听力损失是最常见的感觉缺陷，影响全球 4.66 亿人。涉及的大量和多样化的基因反映了听觉生理学的复杂性，这需要使用动物模型才能更全面地理解。尚未验证基因的位点之一是 DFNA58，其中发现约 200kb 的基因组重复，包括三个编码蛋白的基因（、和 's exon1），与常染色体显性遗传性听力损失分离。通过全基因组测序，发现重复是串联的，并插入一个基因间区域，没有破坏拓扑结构域。对转录组数据研究（斑马鱼和小鼠）的重新分析，以及对成年斑马鱼靶器官的 RT-qPCR 分析，以确定其同源物的表达，突出了有希望的结果，这些结果通过斑马鱼原位杂交和免疫荧光得到了证实。小鼠数据还表明 可能是听觉生理学中一个相关作用的最佳候选基因，其在听力中的重要性似乎仍然保守，但发挥其功能的细胞类型可能已经发生了变化，从毛细胞到螺旋神经节神经元。
