100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.

Background: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.

Functional Associations and Resilience in Microbial Communities.

Microbial communities have inherently high levels of metabolic flexibility and functional redundancy, yet the structure of microbial communities can change rapidly with environmental perturbation. To understand whether such changes observed at the taxonomic level translate into differences at the functional level, we analyzed the structure of taxonomic and functional gene distribution across Arctic and Antarctic locations. Taxonomic diversity (in terms of alpha diversity and species richness) differed significantly with location.

Transcriptome pyrosequencing of the Antarctic brittle star Ophionotus victoriae.

Brittle stars are included within a whole range of species, which contribute to knowledge in the medically important area of tissue regeneration. All brittle stars regenerate lose limbs, but the rate at which this occurs is highly variable and species-specific. One of the slowest rates of arm regeneration reported so far is that of the Antarctic Ophionotus victoriae.

Hypoxia impacts large adults first: consequences in a warming world.

Future oceans are predicted to contain less oxygen than at present. This is because oxygen is less soluble in warmer water and predicted stratification will reduce mixing. Hypoxia in marine environments is thus likely to become more widespread in marine environments and understanding species-responses is important to predicting future impacts on biodiversity.

Differential gene expression during the moult cycle of Antarctic krill (Euphausia superba).

Background: All crustaceans periodically moult to renew their exoskeleton. In krill this involves partial digestion and resorption of the old exoskeleton and synthesis of new cuticle. Molecular events that underlie the moult cycle are poorly understood in calcifying crustaceans and even less so in non-calcifying organisms such as krill.

Surviving the cold: molecular analyses of insect cryoprotective dehydration in the Arctic springtail Megaphorura arctica (Tullberg).

Background: Insects provide tractable models for enhancing our understanding of the physiological and cellular processes that enable survival at extreme low temperatures. They possess three main strategies to survive the cold: freeze tolerance, freeze avoidance or cryoprotective dehydration, of which the latter method is exploited by our model species, the Arctic springtail Megaphorura arctica, formerly Onychiurus arcticus (Tullberg 1876). The physiological mechanisms underlying cryoprotective dehydration have been well characterised in M.

Cold hardening processes in the Antarctic springtail, Cryptopygus antarcticus: clues from a microarray.

The physiology of the Antarctic microarthropod, Cryptopygus antarcticus, has been well studied, particularly with regard to its ability to withstand low winter temperatures. However, the molecular mechanisms underlying this phenomenon are still poorly understood. 1180 sequences (Expressed Sequence Tags or ESTs) were generated and analysed, from populations of C.

urg1: a uracil-regulatable promoter system for fission yeast with short induction and repression times.

Background: The fission yeast Schizosaccharomyces pombe is a popular genetic model organism with powerful experimental tools. The thiamine-regulatable nmt1 promoter and derivatives, which take >15 hours for full induction, are most commonly used for controlled expression of ectopic genes. Given the short cell cycle of fission yeast, however, a promoter system that can be rapidly regulated, similar to the GAL system for budding yeast, would provide a key advantage for many experiments.

Characterisation of the warm acclimated protein gene (wap65) in the Antarctic plunderfish (Harpagifer antarcticus).

Physiological adaptation to increased environmental temperatures has been studied experimentally in a number of fish species, with the up-regulation of several genes identified as being associated with the process, such as the warm-acclimated protein (wap65). This article describes the cloning and characterisation of the wap65-2 gene from the Antarctic plunderfish (Harpagifer antarcticus). The transcriptional expression of this gene in response to elevated seawater temperatures over a time course series is presented.

Global effects on gene expression in fission yeast by silencing and RNA interference machineries.

Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 histone deacetylases, the Clr4 methyltransferase, the zinc finger protein Clr1, and the RNAi proteins Dicer, RdRP, and Argonaute on the transcriptome of Schizosaccharomyces pombe (fission yeast).

Periodic gene expression program of the fission yeast cell cycle.

Cell-cycle control of transcription seems to be universal, but little is known about its global conservation and biological significance. We report on the genome-wide transcriptional program of the Schizosaccharomyces pombe cell cycle, identifying 407 periodically expressed genes of which 136 show high-amplitude changes. These genes cluster in four major waves of expression.

RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress.

Fission yeast Spc1 (Sty1), a stress-activated mitogen-activated protein kinase (MAPK) homologous to human p38, orchestrates global changes in gene expression in response to diverse forms of cytotoxic stress. This control is partly mediated through Atf1, a transcription factor homologous to human ATF2. How Spc1 controls Atf1, and how the cells tailor gene expression patterns to different forms of stress, are unknown.

Whole-genome microarrays of fission yeast: characteristics, accuracy, reproducibility, and processing of array data.

Background: The genome of the fission yeast Schizosaccharomyces pombe has recently been sequenced, setting the stage for the post-genomic era of this increasingly popular model organism. We have built fission yeast microarrays, optimised protocols to improve array performance, and carried out experiments to assess various characteristics of microarrays.

Results: We designed PCR primers to amplify specific probes (180-500 bp) for all known and predicted fission yeast genes, which are printed in duplicate onto separate regions of glass slides together with control elements (approximately 13,000 spots/slide).

Global transcriptional responses of fission yeast to environmental stress.

We explored transcriptional responses of the fission yeast Schizosaccharomyces pombe to various environmental stresses. DNA microarrays were used to characterize changes in expression profiles of all known and predicted genes in response to five stress conditions: oxidative stress caused by hydrogen peroxide, heavy metal stress caused by cadmium, heat shock caused by temperature increase to 39 degrees C, osmotic stress caused by sorbitol, and DNA damage caused by the alkylating agent methylmethane sulfonate. We define a core environmental stress response (CESR) common to all, or most, stresses.

The transcriptional program of meiosis and sporulation in fission yeast.

Sexual reproduction requires meiosis to produce haploid gametes, which in turn can fuse to regenerate a diploid organism. We have studied the transcriptional program that drives this developmental process in Schizosaccharomyces pombe using DNA microarrays. Here we show that hundreds of genes are regulated in successive waves of transcription that correlate with major biological events of meiosis and sporulation.