| 1. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Davies, Neil, et al.
(författare)
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The founding charter of the Genomic Observatories Network
- 2014
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Ingår i: GigaScience. - 2047-217X. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
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| 3. |
- Parnell, John, et al.
(författare)
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Sulfur isotope signatures for rapid colonization of an impact crater by thermophilic microbes
- 2010
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Ingår i: Geology. - 0091-7613 .- 1943-2682. ; 38:3, s. 271-274
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Tidskriftsartikel (refereegranskat)abstract
- In the 23-km-diameter Haughton impact structure, Canadian High Arctic, in sulfate-rich bedrock, widespread hydrothermal sulfide mineralization occurred in breccias formed during the impact. The sulfides exhibit extreme sulfur isotopic fractionation relative to the original sulfate, requiring microbial sulfate reduction by thermophiles throughout the crater. This evidence of widespread microbial activity demonstrates that colonization could occur within the lifetime of a moderately sized, impact-induced hydrothermal system. The pyrite was subsequently oxidized to jarosite, which may also have been microbially mediated. The successful detection of evidence for microbial life suggests that it would be a valuable technique to deploy in sulfate-rich impact terrain on Mars.
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| 4. |
- Bowden, Stephen, et al.
(författare)
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The thermal alteration by pyrolysis of the organic component of small projectiles of mudrock during capture at hypervelocity
- 2008
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Ingår i: Journal of Analytical and Applied Pyrolysis. - : Elsevier BV. - 0165-2370. ; 82, s. 312-314
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Tidskriftsartikel (refereegranskat)abstract
- In a series of experiments the pyrolytic effects of the heating induced during the hypervelocity impact(HVI) of small projectiles of high TOC mudrock were observed. Impacts at these high speeds (km s-1)release sufficient energy to vaporise metal projectiles, and the temperatures created greatly exceed thepyrolysis temperatures typically employed during laboratory studies of the thermal alteration ofsedimentary organic matter. Despite this the organic geochemical analyses of projectiles of OrcadianLaminite impacted into targets of sand and water at hypervelocities provides evidence that the structuralbackbone of biomarkers has remained intact and that only a comparatively low degree of thermalalteration (pre-oil window) has occurred. While further studies are necessary, it appears that the organiccomponent of a projectile captured at hypervelocity will be a slightly thermally altered sample of itsprecursor.
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| 5. |
- Dredge, Ian, et al.
(författare)
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Elevated flux of cosmic spherules (micrometeorites) in Ordovician rocks of the Durness Group, NW Scotland
- 2010
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Ingår i: Scottish Journal of Geology. - : Geological Society of London. - 0036-9276 .- 2041-4951. ; 46, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Limestone samples from the Cambro-Ordovician Durness Group were crushed, acid-digested and searched for evidence of micrometeorites. Eleven melted micrometeorites were extracted from the magnetic fraction of samples from the Balnakeil and Croisaphuill formations near the top of the group. Other formations in the Durness Group did not yield micrometeorites. Only melted spherules with a distinctive dendroidal crystalline structure (I-type cosmic spherules) were accepted as definite micrometeorites. They represent a flux of micrometeorites one to two orders of magnitude greater than at present. The micrometeorite-bearing formations are of Arenig age, coincident with the onset of an enhanced flux of extraterrestrial material identified by the occurrence of fossil meteorites in Sweden.
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| 6. |
- Heap, Graham A., et al.
(författare)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 7. |
- Lindgren, Paula, et al.
(författare)
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A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting
- 2011
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Ingår i: Geochemical Transactions. - : Springer Science and Business Media LLC. - 1467-4866. ; 12, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200 degrees C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials.
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| 8. |
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| 9. |
- Lindgren, Paula, et al.
(författare)
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Concentration of organic matter in hydrothermal deposits
- 2008
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Organic matter with various origins is commonly associated with hydrothermal activity. Examples from the terrestrial record include hydrothermally produced petroleum (Simoneit 1988), the possible formation of abiotic organic molecules (Holm 1992), and present-day biological activity around hydrothermal vents and hot springs (Corliss et al. 1979; Reysenbach and Cady 2001). If the conditions for preservation of the organic matter are favourable, hydrothermal deposits could be suitable sites for the detection of extraterrestrial organic matter, for example on Mars (e.g. Simoneit et al. 1998).The study of hydrothermal deposits in the terrestrial record allows us to gain more knowledge of the distribution of organic matter in various fossil hydrothermal settings. We have investigated fossil hydrothermal deposits on the Isle of Skye in Scotland, where the heat from igneous intrusions (Paleogene dolerite sills) in wet carbon-rich shale (Jurassic) has caused localized hydrothermal activity with the mobilization of organic-rich fluids. Here, the organic matter is accumulated in hydrothermal deposits: It occurs as vesicular hydrocarbon, located in hydrothermal veins together with calcite, chlorite and quartz, and as a cm-dm thick sheet sandwiched between the shale and the intrusive body. Organic matter also occurs in hydrothermally precipitated calcite veins that cross-cuts the igneous intrusion, and in vesicles of the igneous rock.This is one example from the terrestrial record showing that where organic matter is available, it can be mobilised and concentrated as a result of hydrothermal activity. The same process of carbon concentration could have taken place in ancient martian hydrothermal systems, induced by igneous activity or bolide impacts.
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| 10. |
- Lindgren, Paula, et al.
(författare)
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Organic geochemistry of the Haughton Impact Structure
- 2008
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Konferensbidrag (populärvet., debatt m.m.)abstract
- The Haughton Impact Structure (HIS) formed 39 Ma ago. The target rocks include Lower Palaeozoic aged limestone that contain small quantities of solvent extractable organic matter. The target bedrock, hydrothermal deposits and limestone clasts within impact melt breccias all yield fossil organic matter that has been thermally matured to varying degrees. But unusually for a terrestrial impact crater, molecular biomarkers survive. While many other impact structures on Earth (e.g. Gardnos) possess lithologies with associated organic carbon, thermal maturation prior or subsequent to the impact has destroyed any biomarkers that were present (note that this is not necessarily due to the impact itself). In other instances the biomarkers present are found in hydrocarbon accumulations and have migrated through the structure (e.g. Siljan). The HIS is unique in not experiencing subsequent regional metamorphism, furthermore the sedimentary organic matter is mostly present within the target rocks as inclusions of organic matter and not a free continuous petroleum phase (it has not migrated).The extraction and analysis of biomarkers from impactites from the HIS radically alters how an organic geochemist, looking to detect ancient molecular evidence of life, views the surface of a planetary body. For craters of a certain diameter (23 km), impact cratering, far from being an agent that obliterates the biomarker fossil record, can be shown to be a geological process more akin to tectonic activity: it has the potential to exhume geological formations that would otherwise be buried – albeit at the cost of a relatively minor increase in thermal maturity.
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| 11. |
- Lindgren, Paula, 1977-, et al.
(författare)
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Pyrite as a template for carbon fixation
- 2009
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Ingår i: Origins of Life and Evolution of the Biospheres. - Dordrecht : Springer. ; , s. 370-371
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Konferensbidrag (populärvet., debatt m.m.)abstract
- An important process in the evolution of life is the precipitation and concentration of organic species. There are several examples of minerals acting as templates for the accumulation and concentration of organic matter. These include for instance clays (e.g. Cairns-Smith and Hartman, 1986), radioactive minerals (e.g. Rasmussen, et al. 1993), zeolites and feldspars (e.g. Smith, et al. 1999) and the sulphide mineral pyrite (FeS2) (e.g. Wächtershäuser, 1988). Wächtershäuser (1988) suggested that prebiotic chemistry and eventually life itself could have started on the surface of pyrite. Pyrite carries a slight positive electrical charge, and can attract negatively charged organic molecules, bringing them close enough to interact. Pyrite is also oil-wet in some circumstances (Yusupova, 2002). This means that if the mineral is exposed to a mix of oil and water, the oil will preferentially adhere to the surface of pyrite. We have studied migrated organic matter in the Irish Carboniferous, including in sulphide deposits, to assess whether sulphides in fact do act as templates for organics. Here, pyrite was found acting as a template for carbon fixation in hydrothermal calcite veins, cutting through limestone. The pyrite crystals are ca. 1 mm in diameter and scattered throughout the vein matrix. The organic matter is migrated bitumen, and appears as smooth and rounded solid droplets, concentrated around the pyrite crystals. Scanning electron microscope analyses show the organics occurring as a ca. 150 µm thick and even coating around the pyrite crystals. Sulphide templates could be important for carbon fixation on Mars. There is widespread evidence of that sulphur species are prominent in Martian surface environments, assumed to have been introduced to the surface through volcanic activity. Currently, the Martian surface is highly oxidizing and therefore sulphates predominate, but early in the planet’s history reducing conditions pertained. Accordingly it has been suggested that sulphides occurs on Mars (Burns and Fisher, 1990), now preserved at depth. Sulphides are also known to be present on Mars from Martian meteorites (e.g. Greenwood, et al. 2000). Sulphides are sources of fuel for micro-organisms that oxidize sulphides on Earth, and the same could have been the case on Mars (Bishop, et al. 2004). The carbon coated pyrite in this study, is one example from the geological record showing that terrestrial sulphides can have a high potential for the preservation of organic materials. This could also be possible on Mars, and therefore Martian sulphides are good targets for seeking evidence of putative Martian life.
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| 12. |
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| 13. |
- Parnell, John, et al.
(författare)
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Survival of reactive carbon through meteorite impact melting
- 2006
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Ingår i: Geology. - 0091-7613. ; 34:12, s. 1029-1032
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Tidskriftsartikel (refereegranskat)abstract
- Melt fragments in melt breccias from the Gardnos impact crater, Norway, contain abundant carbon. A high proportion of the carbon present in the original melt was preserved. The stripping of hydrogen from carbon during melting prevents later hydrocarbon formation, hence the carbon is fixed in place rather than volatilized. Underlying lithic breccias that were not melted record hydrocarbon generation as a response to less extreme heating. Despite the high-temperature history of the melt, the carbon from the Gardnos impact crater is highly disordered, rather than ordered crystalline graphite, and in this respect, it is comparable with carbon in chondrite chondrules. Disordered carbon bears functional groups upon weathering, and, therefore, carbon preserved through impact or other melting may be available for reworking into biologically relevant organic molecules.
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| 15. |
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