| Autor: |
Nascimento LRD; 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., Vieira-Silva GA; 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., Kitajima JPFW; Mendelics Genomic Analysis, São Paulo 02511-000, Brazil., Batissoco AC; 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., Lezirovitz K; 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. |
| Abstrakt: |
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 ( PLEK , CNRIP1 , and PPP3R1 '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 Cnrip1a, corroborated by zebrafish in situ hybridization and immunofluorescence. Mouse data also suggested Cnrip1 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. |
