Deafness mutation mining using regular expression based pattern matching

<p>Abstract</p> <p>Background</p> <p>While keyword based queries of databases such as Pubmed are frequently of great utility, the ability to use regular expressions in place of a keyword can often improve the results output by such databases. Regular expressions can allow for the identification of element types that cannot be readily specified by a single keyword and can allow for different words with similar character sequences to be distinguished.</p> <p>Results</p> <p>A Perl based utility was developed to allow the use of regular expressions in Pubmed searches, thereby improving the accuracy of the searches.</p> <p>Conclusion</p> <p>This utility was then utilized to create a comprehensive listing of all DFN deafness mutations discussed in Pubmed records containing the keywords "human ear".</p

Myosin Light-Chain Kinase Is Necessary for Membrane Homeostasis in Cochlear Inner Hair Cells

The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a significant decrease in the amplitude of the ABR waves. The mutant inner hair cells produced several ball-like structures around the hair bundles in vivo, indicating impaired membrane stability. Inner hair cells isolated from the knockout mice consistently displayed less resistance to hypoosmotic solution and less membrane F-actin. Myosin light-chain phosphorylation was also reduced in the mutated inner hair cells. Our results suggest that MLCK is necessary for maintaining the membrane stability of inner hair cells

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

At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL), but the knowledge of 121 NSHL-linked chromosomal regions brings to the hypothesis that a number of disease genes have still to be uncovered. To help scientists to find new NSHL genes, we built a gene-scoring system, integrating Gene Ontology, NCBI Gene and Map Viewer databases, which prioritizes the candidate genes according to their probability to cause NSHL. We defined a set of candidates and measured their functional similarity with respect to the disease gene set, computing a score () that relies on the assumption that functionally related genes might contribute to the same (disease) phenotype. A Kolmogorov-Smirnov test, comparing the pair-wise distribution on the disease gene set with the distribution on the remaining human genes, provided a statistical assessment of this assumption. We found at a p-value that the former pair-wise is greater than the latter, justifying a prioritization strategy based on the functional similarity of candidate genes respect to the disease gene set. A cross-validation test measured to what extent the ranking for NSHL is different from a random ordering: adding 15% of the disease genes to the candidate gene set, the ranking of the disease genes in the first eight positions resulted statistically different from a hypergeometric distribution with a p-value and a power. The twenty top-scored genes were finally examined to evaluate their possible involvement in NSHL. We found that half of them are known to be expressed in human inner ear or cochlea and are mainly involved in remodeling and organization of actin formation and maintenance of the cilia and the endocochlear potential. These findings strongly indicate that our metric was able to suggest excellent NSHL candidates to be screened in patients and controls for causative mutations

Isolation and distribution of 1-methyl-5-thiol-L-histidine disulfide and a related metabolite in eggs from echinoderms

Unfertilized eggs of Paracentrotus lividus contained, in addn. to glutathione, large amts. of 1-methyl-5-thiol-L-histidine disulfide. The same amino acid was also isolated from eggs of the sea urchin Arbacia lixula, the holothuroid Holothuria tubulosa, and the asteroids Marthasterias glacialis and Astropecten aurantiacus. Unfertilized eggs of Sphaerechinus granularis contained a related metabolite identified as Nα,Nα,1-trimethyl-5-thiol-L-histidine disulfide on the basis of its spectral and chem. properties

Isolation and distribution of 1-methyl-5-thiol-L-histidine disulfide and a related metabolite in eggs from echinoderms

Unfertilized eggs of Paracentrotus lividus contained, in addn. to glutathione, large amts. of 1-methyl-5-thiol-L-histidine disulfide. The same amino acid was also isolated from eggs of the sea urchin Arbacia lixula, the holothuroid Holothuria tubulosa, and the asteroids Marthasterias glacialis and Astropecten aurantiacus. Unfertilized eggs of Sphaerechinus granularis contained a related metabolite identified as N\u3b1,N\u3b1,1-trimethyl-5-thiol-L-histidine disulfide on the basis of its spectral and chem. properties

Identification of a novel mutation in the myosin VIIA motor domain in a family with autosomal dominant hearing loss (DFNA11)

We ascertained a large Italian family with an autosomal dominant form of non-syndromic sensorineural hearing loss with vestibular involvement. A genome-wide scan found linkage to locus DFNA11. Sequencing of the MYO7A gene in the linked region identified a new missense mutation resulting in an Ala230Val change in the motor domain of the myosin VIIA. Myosin VIIA has already been implicated in several forms of deafness, but this is the third mutation causing a dominant form of deafness, located in the myosin VIIA motor domain in a region never involved in hearing loss until now. A modelled protein structure of myosin VII motor domain provides evidence for a significant functional effect of this missense mutation. Copyright (C) 2006 S. Karger AG, Basel