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- 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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| 2. |
- Loos, Ruth J. F., et al.
(författare)
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Common variants near MC4R are associated with fat mass, weight and risk of obesity
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
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Tidskriftsartikel (refereegranskat)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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| 3. |
- van Stokkum, Ivo H. M., et al.
(författare)
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Inter-pigment interactions in the peridinin chlorophyll protein studied by global and target analysis of time resolved absorption spectra
- 2009
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Ingår i: Chemical Physics. - : Elsevier BV. - 0301-0104. ; 357:1-3, s. 70-78
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Tidskriftsartikel (refereegranskat)abstract
- Inter-pigment interactions define the functioning of light-harvesting protein complexes. To describe the particularly complex molecular dynamics and interactions of peridinin and chlorophyll in the peridinin chlorophyll protein of Amphidinium carterae, we applied global and target analysis to a series of ultrafast transient absorption experiments. We have created and validated a model that consistently describes and characterizes the interactions and evolution of excited and ground-state populations after excitation in all different experiments. The series of energy transfer steps that follow excitation are described by our model of cascading populations and numerous rate constants that correspond to intra-molecular thermal relaxation, fast and slow peridinin-to-chlorophyll energy transfer steps, and chlorophyll excited-state annihilation. By analyzing the spectral response of ground-state peridinins to excited chlorophylls we have identified which specific peridinin molecule is most closely coupled to the chlorophylls. No evidence was found that the intra-molecular charge transfer (ICT) state of peridinin, identified in studies of peridinin in solution, is a separate entity in the protein. The peridinin that exhibited slow peridinin-to-chlorophyll energy transfer was characterized by a difference spectrum free from ICT features, consistent with the importance of coupled ICT and S, states for energy transfer. (c) 2008 Elsevier B.V. All rights reserved.
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