Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population: dHPLC reveals a new candidate mutation

<p>Abstract</p> <p>Background</p> <p>Variants of mitochondrial DNA (mtDNA) have been evaluated for their association with hearing loss. Although ethnic background affects the spectrum of mtDNA variants, systematic mutational analysis of mtDNA in Japanese patients with hearing loss has not been reported.</p> <p>Methods</p> <p>Using denaturing high-performance liquid chromatography combined with direct sequencing and cloning-sequencing, Japanese patients with prelingual (N = 54) or postlingual (N = 80) sensorineural hearing loss not having pathogenic mutations of m.1555A > G and m.3243A > G nor <it>GJB2 </it>were subjected to mutational analysis of mtDNA genes (<it>12S rRNA</it>, <it>tRNA</it>^{<it>Leu(UUR)</it>}, <it>tRNA</it>^{<it>Ser(UCN)</it>}, <it>tRNA</it>^<it>Lys</it>, <it>tRNA</it>^<it>His</it>, <it>tRNA</it>^{<it>Ser(AGY)</it>}, and <it>tRNA</it>^<it>Glu</it>).</p> <p>Results</p> <p>We discovered 15 variants in <it>12S rRNA </it>and one homoplasmic m.7501A > G variant in <it>tRNA</it>^{<it>Ser(UCN)</it>}; no variants were detected in the other genes. Two criteria, namely the low frequency in the controls and the high conservation among animals, selected the m.904C > T and the m.1105T > C variants in <it>12S rRNA </it>as candidate pathogenic mutations. Alterations in the secondary structures of the two variant transcripts as well as that of m.7501A > G in <it>tRNA</it>^{<it>Ser(UCN) </it>}were predicted.</p> <p>Conclusions</p> <p>The m.904C > T variant was found to be a new candidate mutation associated with hearing loss. The m.1105T > C variant is unlikely to be pathogenic. The pathogenicity of the homoplasmic m.7501T > A variant awaits further study.</p

Assessing Occurrence and Biological Consequences of Contaminants of Emerging Concern on Oceanic Islands

Freshwater streams on oceanic islands serve critical ecological and economic functions. However, these are underrepresented in assessments of pollution from contaminants of emerging concern (CEC). Furthermore, freshwater streams and their endemic fauna often have characteristics that are distinct from those of continental streams and model species, calling extrapolations from studies of such systems into question for island streams. In the current study, we assessed the presence of CEC across three sampling events and five freshwater streams on the Island of Hawai&rsquo;i. We also exposed juveniles of the native fish species Sicyopterus stimpsoni to a mixture of commonly co-occurring CEC for 96 h in static renewal experiments, testing for impacts of CEC in two ecologically relevant assays of functional performance. CEC from multiple sources were ubiquitous in Hawaiian streams, including human-use pharmaceuticals, agricultural herbicides, and industrial runoff. Concentrations of CEC were comparable to published studies from continental streams, exceeding total concentrations of 1000 ng/L for the eight quantified CEC in four samples, and approaching 2500 ng/L in one sample. Effects on exposed fish were subtle and limited to treatments with higher CEC concentrations but indicated potential impacts of CEC on locomotor performance. These results indicate that Hawaiian streams follow a global trend of widespread freshwater pollution by CEC that are accompanied by subtle effects on native fish species and highlight the need for the inclusion of endemic species and ecologically relevant assays when assessing the effects of contaminants in island habitats