| 1. |
- Horikoshi, Momoko, et al.
(författare)
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Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.
- 2015
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.
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| 2. |
- Surakka, Ida, et al.
(författare)
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The impact of low-frequency and rare variants on lipid levels.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:6, s. 589-597
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Tidskriftsartikel (refereegranskat)abstract
- Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
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| 3. |
- Redaa, A., et al.
(författare)
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Testing Nano-Powder and Fused-Glass Mineral Reference Materials for In Situ Rb-Sr Dating of Glauconite, Phlogopite, Biotite and Feldspar via LA-ICP-MS/MS
- 2023
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Ingår i: Geostandards and Geoanalytical Research. - : Wiley. - 1639-4488 .- 1751-908X. ; 47:1, s. 23-48
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Tidskriftsartikel (refereegranskat)abstract
- Reference materials (RMs) with well-characterised composition are necessary for reliable quantification and quality control of isotopic analyses of geological samples. For in situ Rb-Sr analysis of silicate minerals via laser ablation inductively coupled plasma tandem mass spectrometry (LA-ICP-MS/MS) with a collision/reaction cell, there is a general lack of mineral-specific and matrix-matched RMs, which limits wider application of this new laser-based dating technique to certain minerals. In this work, pressed nano-powder pellets (NP) of four RMs, GL-O (glauconite), Mica-Mg (phlogopite), Mica-Fe (biotite) and FK-N (K-feldspar), were analysed and tested for in situ Rb-Sr dating, complemented by isotope dilution (ID) MC-ICP-MS Rb-Sr analyses of GL-O and Mica-Mg. In addition, we attempted to develop alternative flux-free and fused 'mineral glasses' from the above RMs for in situ Rb-Sr dating applications. Overall, the results of this study showed that among the above RMs only two NP (Mica-Mg-NP and GL-O-NP) were suitable and robust for in situ dating applications. These two nano-powder reference materials, Mica-Mg-NP and GL-O-NP, were thus used as primary RMs to normalise and determine Rb-Sr ages for three natural minerals: MDC phlogopite and GL-O glauconite grains, and also Mica-Fe-NP (biotite). Our in situ analyses of the above RMs yielded Rb-Sr ages that are in good agreement (within 8%) of published ages, which suggests that both Mica-Mg-NP and GL-O-NP are suitable RMs for in situ Rb-Sr dating of phlogopite, glauconite and biotite. However, using secondary RMs is recommended to monitor the quality of the obtained ages.
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| 4. |
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| 5. |
- Subarkah, D., et al.
(författare)
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Unraveling the histories of Proterozoic shales through in situ Rb-Sr dating and trace element laser ablation analysis
- 2022
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Ingår i: Geology. - : Geological Society of America. - 0091-7613 .- 1943-2682. ; 50:1, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- Authigenic components in marine sediments are important archives for past environment reconstructions. However, defining reliable age constraints and assessing the effects of post depositional overprints in Precambrian sequences are challenging. We demonstrate a new laser-based analytical approach that has the potential to rapidly and accurately evaluate the depositional and alteration histories of Proterozoic shales. Our study employs a novel application of in situ Rb-Sr dating coupled with simultaneous trace-element analysis using reaction-cell laser ablation-inductively coupled plasma-tandem mass spectrometry (LA-ICPMS/MS). We present results from shales sourced from two wells in the Proterozoic McArthur Basin, northern Australia. These rocks have been widely used by previous studies as a key section for ancient biogeochemical and paleo-redox reconstructions. Shales from well UR5 yielded initial Sr-87/Sr-86 ratios, Rb-Sr ages, and rare earth element plus yttrium (REEY) patterns similar to those of a dolerite sampled from the same core. We propose that the UR5 samples chronicle hydrothermal alteration instigated by the dolerite intrusion. In contrast, a correlative shale from well UR6 yielded an age consistent with the expected depositional age (1577 +/- 56 Ma) with REEY and initial Sr-87/Sr-86 ratios similar to ca. 1.5 Ga seawater. We suggest that this sample records the minimum depositional age and early marine diagenetic history for this unit. This new technique can date Proterozoic shales quickly, cheaply, and with minimum sample preparation. Importantly, ages are triaged to differentiate between those recording primary marine versus secondary processes. This novel approach provides a potentially powerful tool for dating and fingerprinting the vast array of ancient marine shales for further studies of Earth systems through deep time.
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| 6. |
- Winters, Mikael, 1976, et al.
(författare)
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Control of electron transfer in a conjugated porphyrin dimer by selective excitation of planar and perpendicular conformers
- 2007
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Ingår i: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 13:26, s. 7385-7394
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Tidskriftsartikel (refereegranskat)abstract
- A donor-acceptor system is presented in which the electron-transfer rates can be sensitively controlled by means of excitation wavelength and temperature. The electron donor is a butadiyne-linked zinc porphyrin dimer that is connected to a C-60 electron acceptor. The broad distribution of conformations allowed by the butadiyne linker makes it possible to selectively excite perpendicular or planar donor conformers and thereby prepare separate initial states with driving forces for electron transfer that differ by almost 0.2 eV This, as well as significant differences in electronic coupling, leads to distinctly different rate constants for electron transfer, which in consequence can be controlled by changing excitation wavelength. By extending the system with a secondary donor (ferrocene), a second, long-range charge-separated state can be formed. This system has been used to test the influence of conformational heterogeneity on electron transfer mediated by the porphyrin dimer in the ground state. It was found that if the dimer is forced to a planar conformation by means of a bidentate ligand, the charge recombination rate increased by an order of magnitude relative to the unconstrained system. This illustrates how control of conformation of a molecular wire can affect its behaviour.
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| 7. |
- Winters, Mikael, 1976, et al.
(författare)
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Probing the efficiency of electron transfer through porphyrin-based molecular wires
- 2007
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 129:14, s. 4291-4297
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Tidskriftsartikel (refereegranskat)abstract
- Electron transfer over long distances is important for many future applications in molecular electronics and solar energy harvesting. In these contexts, it is of great interest to find molecular systems that are able to efficiently mediate electrons in a controlled manner over nanometer distances, that is, structures that function as molecular wires. Here we investigate a series of butadiyne-linked porphyrin oligomers with ferrocene and fullerene (C-60) terminals separated by one, two, or four porphyrin units (P-n, n = 1, 2, or 4). When the porphyrin oligomer bridges are photoexcited, long-range charge separated states are formed through a series of electron-transfer steps and the rates of photoinduced charge separation and charge recombination in these systems were elucidated using time-resolved absorption and emission measurements. The rates of long-range charge recombination, through these conjugated porphyrin oligomers, are remarkably fast (k(CR2) = 15 - 1.3 x 10(8) s(-1)) and exhibit very weak distance dependence, particularly comparing the systems with n = 2 and n = 4. The observation that the porphyrin tetramer mediates fast long-range charge transfer, over 65 angstrom, is significant for the application of these structures as molecular wires.
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