Similar Datasets
Project description:A large number of congenital hearing loss cases have an unknown genetic etiology. So far, transcriptomic approaches have successfully identified many candidate regulators of otic development, little is known about the abundance of their protein products during the development of the inner eat. Herein we used a multiplexed quantitative mass spectrometry-based proteomic approach to determine temporal trends in protein abundances during inner ear (otic) development in Xenopus. Wild type Xenopus embryos were cultured to larval stages and their otic tissues were manually dissected at five stages that represent that represent key transitions in otic morphology. The samples were processed using a bottom-up proteomic workflow and analyzed using LC-MS3.The analysis revealed dynamic expression of proteins related to cytoskeletal regulation, integrin signaling, and the extracellular matrix as inner ear structures developed. We correlated the dynamically regulated proteins in our dataset with previously published putative downstream targets of syndromic hearing loss genes SIX1 and CHD7 to identify novel candidate genes for congenital hearing loss.
2023-10-24 | PXD041991 | Pride
Project description:Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. In many cases, congenital hearing loss is ultimately attributed to viral infection, most often by cytomegalovirus (CMV), but also in Congenital Zika Syndrome (CZS). The mechanisms by which CMV and ZIKV virus cause these cranial developmental defects have not been elucidated. Inner ear development has been particularly difficult to study, given the inaccessibility and scarcity of the tissue in animal models or on human autopsy; however, it is now possible to culture stem-cell derived otic progenitor cells (OPCs). Here we describe successful in-vitro infection of OPCs with either CMV or ZIKV. We find that ZIKV infection rapidly and strongly induces the expression of type I IFN and inflammatory genes, while simultaneously decreasing otic cell viability in culture that is at least in part attributable to apoptosis. In contrast, CMV infection did not appear to elicit either of these effects and instead demonstrated a clear dysregulation of the expression of many key genes and pathways associated with inner ear development and function, including Cochlin, NGFR, SOX11 and TGF-β signaling. These findings suggest that ZIKV and CMV infections cause congenital hearing loss through very different pathways; that is, by killing progenitor cells in the case of ZIKV infection, and via disruption of critical developmental pathways in the case of CMV infection. In addition to demonstrating differential hCMV and ZIKV pathogenesis mechanisms in OPCs, this study highlights the advantages of otic progenitor cell models for the study of congenital hearing loss induced by viral infection.
2024-01-18 | GSE234062 | GEO
Project description:This study investigates how lead exposure triggers cochlear synaptopathy and hearing loss in mice. Young-adult CBA/J mice were given lead acetate in drinking water for 28 days. We assessed hearing thresholds, outer hair cell activity, and synaptic changes in the cochlea. Lead exposure raises hearing thresholds, indicating cochlear synaptopathy. Notably affects synapses in the basal turn without impacting outer hair cells. In addition to this, lead altered the abundance of 352 synaptic proteins, with the synaptic vesicle cycle pathway prominently affected. Lead-induced cochlear synaptopathy targets basal cochlear regions, implicating synaptic vesicle cycle signaling in hearing loss. Revealing specific mechanisms behind lead-induced hearing deficits enhances targeted interventions and preventive strategies, advancing our understanding of lead induced hearing loss.
2024-10-17 | PXD050415 | Pride
Project description:Objectives: Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss. This pilot study underpins a larger effort that involves the stage-wise analysis of hearing loss patients, many of whom have advanced to high-throughput sequencing analysis. Data description: Our data originate from Infinium HumanOmni1-Quad v1.0 SNP-microarrays (Illumina) that provide useful markers for genome-wide association studies and copy number variation analysis. This dataset comprises a cohort of 108 individuals (99 with hearing loss, 9 normal hearing family members) for the purpose of understanding the genetic contribution of copy number variations to hereditary hearing loss.
2018-03-06 | GSE111131 | GEO
Project description:Background The genetic diversity of loci and mutations underlying hereditary hearing loss is an active area of investigation. To identify loci associated with predominantly non-syndromic sensorineural hearing loss, we performed exome sequencing of families and of single probands, as well as copy number variation (CNV) mapping in a case-control cohort. Results Analysis of three distinct families revealed several candidate loci in two families and a single strong candidate gene, MYH7B, for hearing loss in one family. MYH7B encodes a Type II myosin, consistent with a role for cytoskeletal proteins in hearing. High-resolution genome-wide CNV analysis of 150 cases and 157 controls revealed deletions in genes known to be involved in hearing (e.g. GJB6, OTOA, and STRC, encoding connexin 30, otoancorin, and stereocilin, respectively), supporting CNV contributions to hearing loss phenotypes. Additionally, a novel region on chromosome 16 containing part of the PDXDC1 gene was found to be frequently deleted in hearing loss patients (OR = 3.91, 95% CI: 1.62-9.40, p = 1.45 x 10-7). Conclusions We conclude that many known as well as novel loci and distinct types of mutations not typically tested in clinical settings can contribute to the etiology of hearing loss. Our study also demonstrates the challenges of exome sequencing and genome-wide CNV mapping for direct clinical application, and illustrates the need for functional and clinical follow-up as well as curated open-access databases. Single replicates of 151 non-syndromic hereditary hearing loss cases and 157 controls with normal hearing were analyzed.
2014-12-19 | E-GEOD-64088 | biostudies-arrayexpress
Project description:Background The genetic diversity of loci and mutations underlying hereditary hearing loss is an active area of investigation. To identify loci associated with predominantly non-syndromic sensorineural hearing loss, we performed exome sequencing of families and of single probands, as well as copy number variation (CNV) mapping in a case-control cohort. Results Analysis of three distinct families revealed several candidate loci in two families and a single strong candidate gene, MYH7B, for hearing loss in one family. MYH7B encodes a Type II myosin, consistent with a role for cytoskeletal proteins in hearing. High-resolution genome-wide CNV analysis of 150 cases and 157 controls revealed deletions in genes known to be involved in hearing (e.g. GJB6, OTOA, and STRC, encoding connexin 30, otoancorin, and stereocilin, respectively), supporting CNV contributions to hearing loss phenotypes. Additionally, a novel region on chromosome 16 containing part of the PDXDC1 gene was found to be frequently deleted in hearing loss patients (OR = 3.91, 95% CI: 1.62-9.40, p = 1.45 x 10-7). Conclusions We conclude that many known as well as novel loci and distinct types of mutations not typically tested in clinical settings can contribute to the etiology of hearing loss. Our study also demonstrates the challenges of exome sequencing and genome-wide CNV mapping for direct clinical application, and illustrates the need for functional and clinical follow-up as well as curated open-access databases.
2014-12-19 | GSE64088 | GEO
Project description:Progressive Hearing Loss
| EGAD00001000197 | EGA