| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Birney, Ewan, et al.
(författare)
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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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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)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. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 4. |
- Fynbo, H. O. U., et al.
(författare)
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Revised rates for the stellar triple-alpha process from measurement of C-12 nuclear resonances
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687 .- 1476-4679. ; 433:7022, s. 136-139
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Tidskriftsartikel (refereegranskat)abstract
- In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form C-12 because of a resonant reaction leading to a nuclear excited state(1). (Stars with masses greater than similar to0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.) Although the reaction rate is of critical significance for determining elemental abundances in the Universe(1), and for determining the size of the iron core of a star just before it goes supernova(2), it has hitherto been insufficiently determined(2). Here we report a measurement of the inverse process, where a C-12 nucleus decays to three alpha-particles. We find a dominant resonance at an energy of similar to11 MeV, but do not confirm the presence of a resonance at 9.1 MeV (ref. 3). We show that interference between two resonances has important effects on our measured spectrum. Using these data, we calculate the triple-a rate for temperatures from 10(7) K to 10(10) K and find significant deviations from the standard rates(3). Our rate below similar to5 x 10(7) K is higher than the previous standard, implying that the critical amounts of carbon that catalysed hydrogen burning in the first stars are produced twice as fast as previously believed(4). At temperatures above 10(9) K, our rate is much less, which modifies predicted nucleosynthesis in supernovae(5,6).
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| 5. |
- Alcorta, M., et al.
(författare)
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Nuclear Structure of C-12 from Break-up Studies in Complete Kinematics
- 2009
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Ingår i: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. - 9780735407022 ; 1165, s. 27-30 461
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Konferensbidrag (refereegranskat)abstract
- A complete kinematics study of the B-10(He-3,p alpha alpha alpha) and B-11(He-3,d alpha alpha alpha) reactions has been performed to study the multi-particle break-up of C-12 resonances above the triple-alpha threshold. Four-particle coincidence detection gives us complete information on the direction and energy of the individual alpha particles from the decay of C-12, allowing us to extract new information on the structure of C-12 which we shall present in this contribution. We have observed gamma de-excitation of the T=1 15.11 MeV resonance using charged particle detectors, and have constructed Dalitz plots of the individual resonances in C-12 using the complete kinematics information of the alpha particles which come from their break-up.
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| 6. |
- Diget, C. A., et al.
(författare)
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Properties of the C-12 10 MeV state determined through beta-decay
- 2005
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 760:1-2, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- The beta-delayed triple-alpha particle decay of B-12 has been measured with a setup that favours coincidence detection. A broad state in C-12, previously reported around 10 MeV, has been seen and its properties determined through R-matrix analysis of the excitation spectrum. The spin and parity are 0(+). Interference between this state and the Hoyle state at 7.654 MeV has a marked influence on the spectrum. The coupling between the two states makes it difficult to determine the resonance energy. (c) 2005 Elsevier B.V. All rights reserved.
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| 7. |
- Hyldegaard, S., et al.
(författare)
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Branching ratios in the beta decays of N-12 and B-12
- 2009
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 80:4
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Tidskriftsartikel (refereegranskat)abstract
- Absolute branching ratios to unbound states in C-12 populated in the beta decays of N-12 and B-12 are reported. Clean sources of N-12 and B-12 were obtained using the isotope separation on-line (ISOL) method. The relative branching ratios to the different populated states were extracted using single-alpha as well as complete kinematics triple-alpha spectra. These two largely independent methods give consistent results. Absolute normalization is achieved via the precisely known absolute branching ratio to the bound 4.44 MeV state in C-12. The extracted branching ratios to the unbound states are a factor of three more precise than previous measurements. Branching ratios in the decay of Na-20 are also extracted and used to check the results.
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| 8. |
- Kirsebom, O. S., et al.
(författare)
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Observation of gamma-delayed 3 alpha breakup of the 15.11 and 12.71 MeV states in C-12
- 2009
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 680:1, s. 44-49
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Tidskriftsartikel (refereegranskat)abstract
- The reactions B-10(He-3, p alpha alpha alpha) at 4.9 MeV and B-11(He-3, d alpha alpha alpha) at 8.5 MeV have been used to investigate the gamma decay of states in C-12. By measuring the four-body final state in complete kinematics we are able to detect gamma transitions indirectly. We find gamma transitions from the 15.11 MeV state in C-12 to the 12.71, 11.83, 10.3 and 7.65 MeV states followed by their breakup into three alpha particles. The relative gamma-ray branching ratios obtained are (1.2 +/- 0.3), (0.32 +/- 0.12), (1.4 +/- 0.2) and (4.4 +/- 0.8)%, respectively, with the remaining (92.7 +/- 1.0)% of the gamma decays going to the bound states. We obtain Gamma(alpha)/Gamma = (2.8 +/- 1.2)% for the isospinforbidden alpha decay of the 15.11 MeV state. From the 12.71 MeV state we find gamma transitions to the 10.3 and 7.65 MeV states. The relative gamma-ray branching ratios are (0.9(-0.5)(+0.6)) and (2.6(-1.2)(+1.6))%, respectively, with the remaining (96.6(-1.3)(+1.7))% of the gamma decays going to the bound states. Finally. we discuss the relation between the beta decay of N-12 and B-12 to states in C-12 and the gamma decay of the 15.11 MeV analog in C-12 to the same states. (C) 2009 Elsevier B.V. All rights reserved.
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| 9. |
- Knudsen, H. H., et al.
(författare)
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Beta-decay of 13O
- 2005
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 72:4, s. 044312-
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Tidskriftsartikel (refereegranskat)abstract
- The beta decay of O-13 has been studied at the IGISOL facility of the Jyvaskyla accelerator centre (Finland). By developing a low-energy isotope-separated beam of O-13 and using a modern segmented charged-particle detector array an improved measurement of the delayed proton spectrum was possible. Protons with energy up to more than 12 MeV are measured and the corresponding log(ft) values extracted. A revised decay scheme is constructed. The connection to molecular states and the shell model is discussed.
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| 10. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)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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