| 1. |
- Sodergren, Erica, et al.
(author)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Journal article (peer-reviewed)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 2. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 4. |
- Anderson, Ian, et al.
(author)
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Shakra: tracking and sharing daily activity levels with unaugmented mobile phones
- 2007
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In: Mobile Networks and Applications. - : Springer Science and Business Media LLC. - 1383-469X .- 1572-8153. ; 12:2-3, s. 185-199
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Journal article (peer-reviewed)abstract
- This paper explores the potential for use of an unaugmented commodity technology—the mobile phone— as a health promotion tool. We describe a prototype application that tracks the daily exercise activities of people, using an Artificial Neural Network (ANN) to analyse GSM cell signal strength and visibility to estimate a user’s movement. In a short-term study of the prototype that shared activity information amongst groups of friends, we found that awareness encouraged reflection on, and increased motivation for, daily activity. The study raised concerns regarding the reliability of ANN-facilitated activity detection in the ‘real world’. We describe some of the details of the pilot study and introduce a promising new approach to activity detection that has been developed in response to some of the issues raised by the pilot study, involving Hidden Markov Models (HMM), task modelling and unsupervised calibration. We conclude with our intended plans to develop the system further in order to carry out a longer-term clinical trial.
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| 5. |
- Braun, Matthias, et al.
(author)
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Comparison of remote sensing derived glacier facies maps with distributed mass balance modelling at Engabreen, northern Norway
- 2007
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In: Glacier Mass Balance Changes and Meltwater Discharge. - Wallingford : IAHS. - 9781901502398 ; , s. 126-134:318, s. 126-134
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Conference paper (peer-reviewed)abstract
- Calibration and validation of glacier mass balance models typically rely on mass balance data derived from measurements at individual points, often along altitudinal gradients, thus neglecting much of the spatial variability of mass balance. Remote sensing data can provide useful additional spatially distributed information, e.g. on surface conditions such as bare ice area, firn cover extent, or snow. We developed a semi-automated procedure to derive glacier-facies maps from Landsat satellite images, and applied it to Engabreen, an outlet glacier from the Svartisen ice cap in northern Norway. These maps, discriminating between firn, snow and ice surfaces, are then used as a reference for mass balance modelling. Facies information shows a general agreement with the available few field observations and results obtained by distributed mass balance modelling. We conclude that Earth Observation products provide a powerful, although as yet poorly exploited tool, for calibration and validation of distributed mass balance models.
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| 6. |
- Brown, Ian, et al.
(author)
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Investigation of the spatial variations in Synthetic Aperture Radar backscatter in western Dronning Maud Land, Antarctica
- 2008
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In: Journal of Applied Remote Sensing. ; 2:023509
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Journal article (peer-reviewed)abstract
- C-band SAR observations show that backscatter varies significantly across small scales (tens of kilometers) in western Dronning Maud Land. Generally, backscatter was found to diminish with altitude reflecting lower accumulation and reduced ice inclusions in the firn of the percolation zone at higher elevations. Reference to (incomplete) mass balance data suggests an anticorrelation between backscatter and net balance, although more data are needed to confirm the trend. Even within the percolation zone, areas of low backscatter (<-12 dB) exist. These are uncorrelated with altitude above sea level. Using a Rayleigh backscatter model, we show that backscatter over such regions may represent differences in grain sizes. The application of a buried-layers model did not accurately estimate backscatter from these regions. We suggest that these regions occupy exposed positions subject to increased wind sublimation which, in turn, results in smaller grain sizes in the firn and therefore reduced backscatter. The Radarsat Antarctica Mapping Mission SAR mosaic indicates such regions occur in Coates Land, near the edge of the Antarctic Plateau, and on exposed promontories elsewhere in East Antarctica. More information regarding the structure of the firn and the mass balance of the region is needed before we can definitively explain controls on backscatter and understand the climatology of the low backscatter zones.
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| 7. |
- Butler, Geraldine, et al.
(author)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Journal article (peer-reviewed)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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| 8. |
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| 9. |
- Loos, Ruth J. F., et al.
(author)
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Common variants near MC4R are associated with fat mass, weight and risk of obesity
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
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Journal article (peer-reviewed)abstract
- To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
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| 10. |
- Margulies, Elliott H, et al.
(author)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Journal article (peer-reviewed)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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