Finding New Genes for Non-Syndromic Hearing Loss through an In Silico Prioritization Study

Accetturo, Matteo; Creanza, Teresa Maria; Santoro, Claudia; Tria, Giancarlo; Giordano, Antonio; Battagliero, Simone; Vaccina, Antonella; Scioscia, Gaetano; Leo, Pietro

doi:10.1371/journal.pone.0012742

Cited by 12 publications

(6 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This protein has been identified as a potential candidate autoantigen in autoimmune inner ear disease (Boulassel et al, 2000). Moreover, beta actin mutations altering depolymerization dynamics are associated with autosomal dominant deafness, and dystonia and with non‐syndromic hearing loss (Procaccio et al, 2006; Accetturo et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Proteomics in Ménière disease

Chiarella

Saccomanno

Scumaci

et al. 2011

Journal Cellular Physiology

View full text Add to dashboard Cite

Ménière's disease (MD) is a disorder of the inner ear characterized by an insidious onset and aspecific symptoms, such as dizziness, vertigo, tinnitus, and hearing loss, that may become very debilitating. The presence of endolymphatic hydrops is a common feature in MD patients, but the pathophysiology is still largely unknown. In this study, we have used a proteomics-driven approach to identify potential biomarkers of MD. To this end, plasma was obtained from whole blood of 16 individuals previously diagnosed as suffering from MD and compared to plasma from healthy donors. A depletion of the highly abundant proteins (i.e., albumin, IgG, transferrin, etc.) was performed in order to enhance the chance of detection of the less represented ones, therefore reducing the noise-background. Two-dimensional gel electrophoresis, followed by in-gel tryptic digestion of the selected spots and LC-MS/MS analysis, allowed us to identify a set of proteins whose expression appears to be differentially modulated in patients versus controls. In particular: complement factor H and B, fibrinogen alpha and gamma chains, beta-actin and pigment epithelium derived factor are over expressed; on the other hand, the levels of beta-2 glycoprotein-1, vitamin D binding protein and apolipoprotein-1 are significantly decreased in the plasma of MD-affected individuals. Even though preliminary and not necessarily linked directly to the molecular pathogenesis of the disease, our original findings suggest that a molecular signature, represented by the plasma protein profile previously described, might represent a potentially powerful, innovative and not invasive tool for early diagnosis and clinical management of MD patients. J. Cell. Physiol. 227: 308-312, 2012. © 2011 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomics in Ménière disease

Chiarella

Saccomanno

Scumaci

et al. 2011

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…To date, 144 loci and 63 genes are known to be involved in human nonsyndromic hearing loss (NSHL), where deafness occurs without other symptoms (http://hereditaryhearingloss.org; Accetturo et al. ; Yan and Liu ; Lenz and Avraham ). This includes recessive, dominant, X‐ and Y‐linked and mitochondrial mutations (Lenz and Avraham ).…”

Section: Introductionmentioning

confidence: 99%

A phylomedicine approach to understanding the evolution of auditory sensory perception and disease in mammals

Kirwan

Bekaert

Commins

et al. 2013

Evolutionary Applications

View full text Add to dashboard Cite

Hereditary deafness affects 0.1% of individuals globally and is considered as one of the most debilitating diseases of man. Despite recent advances, the molecular basis of normal auditory function is not fully understood and little is known about the contribution of single-nucleotide variations to the disease. Using crossspecies comparisons of 11 'deafness' genes (Myo15, Ush1 g, Strc, Tecta, Tectb, Otog, Col11a2, Gjb2, Cldn14, Kcnq4, Pou3f4) across 69 evolutionary and ecologically divergent mammals, we elucidated whether there was evidence for: (i) adaptive evolution acting on these genes across mammals with similar hearing capabilities; and, (ii) regions of long-term evolutionary conservation within which we predict disease-associated mutations should occur. We find evidence of adaptive evolution acting on the eutherian mammals in Myo15, Otog and Tecta. Examination of selection pressures in Tecta and Pou3f4 across a taxonomic sample that included a wide representation of auditory specialists, the bats, did not uncover any evidence for a role in echolocation. We generated 'conservation indices' based on selection estimates at nucleotide sites and found that known disease mutations fall within sites of high evolutionary conservation. We suggest that methods such as this, derived from estimates of evolutionary conservation using phylogenetically divergent taxa, will help to differentiate between deleterious and benign mutations.

show abstract

“…The molecular basis of mammalian hearing involves over 50 candidate genes identified via studies of mutagenesis and non-syndromic hearing loss (Accetturo et al, 2010;Dror and Avraham, 2010). The mammalian hearing apparatus has evolved into a wide range of auditory systems, the most specialised of which arguably occur in echolocating bats and cetaceans (Vater and Kossl, 2004).…”

Section: Introductionmentioning

confidence: 99%

Parallel signatures of sequence evolution among hearing genes in echolocating mammals: an emerging model of genetic convergence

et al. 2011

View full text Add to dashboard Cite

Recent findings of sequence convergence in the Prestin gene among some bats and cetaceans suggest that parallel adaptations for high-frequency hearing have taken place during the evolution of echolocation. To determine if this gene is an exception, or instead similar processes have occurred in other hearing genes, we have examined Tmc1 and Pjvk, both of which are associated with non-syndromic hearing loss in mammals. These genes were amplified and sequenced from a number of mammalian species, including echolocating and non-echolocating bats and whales, and were analysed together with published sequences. Sections of both genes showed phylogenetic signals that conflicted with accepted species relationships, with coding regions uniting laryngeal echolocating bats in a monophyletic clade. Bayesian estimates of posterior probabilities of convergent and divergent substitutions provided more direct evidence of sequence convergence between the two groups of laryngeal echolocating bats as well as between echolocating bats and dolphins. We found strong evidence of positive selection acting on some echolocating bat species and echolocating cetaceans, contrasting with purifying selection on non-echolocating bats. Signatures of sequence convergence and molecular adaptation in two additional hearing genes suggest that the acquisition of high-frequency hearing has involved multiple loci.

show abstract

Finding New Genes for Non-Syndromic Hearing Loss through an In Silico Prioritization Study

Cited by 12 publications

References 86 publications

Proteomics in Ménière disease

Proteomics in Ménière disease

A phylomedicine approach to understanding the evolution of auditory sensory perception and disease in mammals

Parallel signatures of sequence evolution among hearing genes in echolocating mammals: an emerging model of genetic convergence

Contact Info

Product

Resources

About