RESUMEN
MicroRNAs are a class of important post-transcriptional regulators. Genetic and somatic mutations in miRNAs, especially those in the seed regions, have profound and broad impacts on gene expression and physiological and pathological processes. Over 500 SNPs were mapped to the miRNA seeds, which are located at position 2-8 of the mature miRNA sequences. We found that the central positions of the miRNA seeds contain fewer genetic variants and therefore are more evolutionary conserved than the peripheral positions in the seeds. We developed a knowledgebased method to analyse the functional impacts of mutations in miRNA seed regions. We computed the gene ontology-based similarity score GOSS and the GOSS percentile score for all 517 SNPs in miRNA seeds. In addition to the annotation of SNPs for their functional effects, in the present article we also present a detailed analysis pipeline for finding the key functional changes for seed SNPs. We performed a detailed gene ontology graph-based analysis of enriched functional categories for miRNA target gene sets. In the analysis of a SNP in the seed region of hsa-miR-96 we found that two key biological processes for progressive hearing loss 'Neurotrophin TRK receptor signaling pathway' and 'Epidermal growth factor receptor signaling pathway' were significantly and differentially enriched by the two sets of allele-specific target genes of miRNA hsa-miR-96.
Asunto(s)
Algoritmos , Receptores ErbB/genética , Pérdida Auditiva Funcional/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Receptor trkA/genética , Alelos , Receptores ErbB/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Pérdida Auditiva Funcional/metabolismo , Pérdida Auditiva Funcional/patología , Humanos , MicroARNs/metabolismo , Anotación de Secuencia Molecular , Mutación , Receptor trkA/metabolismo , Transducción de SeñalRESUMEN
Nonorganic hearing loss is a decrease in hearing that is unexplained by anatomic or physiologic abnormalities, or both. The term is synonymous with functional hearing loss and pseudohypacusis. The demographics and potential etiologies of nonorganic hearing loss are described. History and physical findings that indicate a functional hearing loss are also discussed. A review of the anatomy and physiology of the auditory system is provided as a background for the discussed objective tests of hearing thresholds. Finally, conditions that may mimic functional hearing loss are described in detail.