In a paper published in this week's PNAS Early Edition, investigators at the University of Iowa describe their use of target enrichment sequencing to screen for causative mutations associated with hereditary hearing loss in six individuals. The Iowa team identified a purportedly pathogenic mutation in five of the six idiopathic samples they sequenced using "solid-phase (NimbleGen) or solution-based (SureSelect) sequence capture, followed by 454 or Illumina sequencing, respectively," the authors write, adding that these technologies "provide sensitivity, specificity, and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss."
Ohio State University's Carlo Croce and his colleagues show in PNAS this week that miR-21 "targets and down-regulates the core mismatch repair recognition protein complex, human mutS homolog 2 and 6" and that over-expression of the non-coding RNA is associated with "significantly reduced 5-fluorouracil-induced G2/M damage arrest and apoptosis that is characteristic of defects in the core MMR component." In xenograft studies, the team also found that "miR-21 overexpression dramatically reduces the therapeutic efficacy of 5-FU." Croce et al. propose that the down-regulation of the miR-21-associated MMR mutator gene could be an indicator of 5-fluorouracil therapeutic efficacy of in the clinic.
Using comparative genomics approaches, an international research team characterizes the genomes of the Vibrio mimicus clinical isolate MB451 and environmental isolate VM223, relatives of the cholera-causing bacteria. The team identified "extensive genomic rearrangement in C-II," which they say implicates it as a "hot spot for evolution and genesis of speciation for the genus Vibrio." The team also found "no notable difference in potential virulence genes" between the isolates they investigated.
Researchers at Princeton University, along with their colleagues, discuss "RNA-mediated epigenetic regulation of DNA copy number" in PNAS this week. In the ciliate Oxytricha, the team writes, "RNA molecules present in parental cells during sexual reproduction can regulate chromosome copy number in the developing nucleus." By inducing changes in RNA abundance, the team was able to both "increase and decrease the levels of corresponding DNA molecules in progeny," which they say demonstrates a way in which chromosome copy number can be inherited epigenetically.
And statisticians and systems biologists at Harvard and their collaborators suggest that the editorial staff at PNAS ought to "reconceptualize the organization of papers" it publishes. Using machine-learning techniques, the researchers found, among other things, that "the number of articles that are listed under multiple categories is only a small fraction of what it should be."