Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Inhibition of Mitochondrial Division Attenuates Cisplatin-Induced Toxicity in the Neuromast Hair Cells

Cisplatin and other related platinum antineoplastic drugs are commonly used in the treatment of a variety of cancers in both adults and children but are often associated with severe side effects, including hearing loss. Cisplatin’s ototoxic effects are multifaceted, culminating in irreversible damage to the mechanosensory hair cells in the inner ear. Platinum drugs act on cancerous cells by forming nuclear DNA adducts, which may initiate signaling leading to cell cycle arrest or apoptosis. Moreover, it was reported that cisplatin may induce mitochondrial DNA damage in non-cancerous cells. Therefore, protecting mitochondria may alleviate cisplatin-induced insult to non-proliferating cells. Thus, it is important to identify agents that shield the mitochondria from cisplatin-induced insult without compromising the anti-tumor actions of the platinum-based drugs. In this study we tested the protective properties of mitochondrial division inhibitor, mdivi-1, a derivative of quinazolinone and a regulator of mitochondrial fission. Interestingly, it has been reported that mdivi-1 increases the apoptosis of cells that are resistant to cisplatin. The ability of mdivi-1 to protect hair cells against cisplatin-induced toxicity was evaluated in a fish model. Wild-type (Tübingen strain), cdh23 mutant, and transgenic pvalb3b::GFP zebrafish stably expressing GFP in the hair cells were used in this study. Larvae at 5–6 days post fertilization were placed in varying concentrations of cisplatin (50–200 μM) and/or mdivi-1 (1–10 μM) for 16 h. To evaluate hair cell’s viability the number of hair bundles per neuromast were counted. To assess hair cell function, we used the FM1-43 uptake assay and recordings of neuromast microphonic potentials. The results showed that mdivi-1 protected hair cells of lateral line neuromasts when they were challenged by 50 μM of cisplatin: viability of hair cells increased almost twice from 19% ± 1.8% to 36% ± 2.0% (p < 0.001). No protection was observed when higher concentrations of cisplatin were used. In addition, our data were in accord with previously reported results that functional mechanotransduction strongly potentiates cisplatin-induced hair cell toxicity. Together, our results suggest that mitochondrial protection may prevent cisplatin-induced damage to hair cells

COS Ambassadors

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