| 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. |
- Fischer, Debra A., et al.
(författare)
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M2K. II. A Triple-Planet System Orbiting Hip 57274
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 745:1, s. 21-
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Tidskriftsartikel (refereegranskat)abstract
- Doppler observations from Keck Observatory have revealed a triple-planet system orbiting the nearby K4V star, HIP 57274. The inner planet, HIP 57274b, is a super-Earth with M sin i = 11.6 M-circle plus (0.036 M-Jup), an orbital period of 8.135 +/- 0.004 days, and slightly eccentric orbit e = 0.19 +/- 0.1. We calculate a transit probability of 6.5% for the inner planet. The second planet has M sin i = 0.4 M-Jup with an orbital period of 32.0 +/- 0.02 days in a nearly circular orbit (e = 0.05 +/- 0.03). The third planet has M sin i = 0.53 M-Jup with an orbital period of 432 +/- 8 days (1.18 years) and an eccentricity e = 0.23 +/- 0.03. This discovery adds to the number of super-Earth mass planets with M sin i < 12 M-circle plus that have been detected with Doppler surveys. We find that 56% +/- 18% of super-Earths are members of multi-planet systems. This is certainly a lower limit because of observational detectability limits, yet significantly higher than the fraction of Jupiter mass exoplanets, 20% +/- 8%, that are members of Doppler-detected, multi-planet systems.
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| 3. |
- Howard, Andrew W., et al.
(författare)
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The California planet survey. I. four new giant exoplanets
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 721:2, s. 1467-1481
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Tidskriftsartikel (refereegranskat)abstract
- We present precise Doppler measurements of four stars obtained during the past decade at Keck Observatory by the California Planet Survey (CPS). These stars, namely, HD 34445, HD 126614, HD 13931, and Gl 179, all show evidence for a single planet in Keplerian motion. We also present Doppler measurements from the Hobby-Eberly Telescope (HET) for two of the stars, HD 34445 and Gl 179, that confirm the Keck detections and significantly refine the orbital parameters. These planets add to the statistical properties of giant planets orbiting near or beyond the ice line, and merit follow-up by astrometry, imaging, and space-borne spectroscopy. Their orbital parameters span wide ranges of planetary minimum mass (M sin i = 0.38-1.9 M-Jup), orbital period (P = 2.87-11.5 yr), semimajor axis (a = 2.1-5.2 AU), and eccentricity (e = 0.02-0.41). HD 34445 b (P = 2.87 yr, M sin i = 0.79 MJup, e = 0.27) is a massive planet orbiting an old, G-type star. We announce a planet, HD 126614 Ab, and an M dwarf, HD 126614 B, orbiting the metal-rich star HD 126614 (which we now refer to as HD 126614 A). The planet, HD 126614 Ab, has minimum mass M sin i = 0.38 MJup and orbits the stellar primary with period P = 3.41 yr and orbital separation a = 2.3 AU. The faint M dwarf companion, HD 126614 B, is separated from the stellar primary by 489 mas (33 AU) and was discovered with direct observations using adaptive optics and the PHARO camera at Palomar Observatory. The stellar primary in this new system, HD 126614 A, has the highest measured metallicity ([ Fe/ H] = + 0.56) of any known planet-bearing star. HD 13931 b (P = 11.5 yr, M sin i = 1.88 MJup, e = 0.02) is a Jupiter analog orbiting a near solar twin. Gl 179 b (P = 6.3 yr, M sin i = 0.82 M-Jup, e = 0.21) is a massive planet orbiting a faint M dwarf. The high metallicity of Gl 179 is consistent with the planet-metallicity correlation among M dwarfs, as documented recently by Johnson & Apps.
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| 4. |
- Howard, Andrew W., et al.
(författare)
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The NASA-UC Eia-earth program. II. a planet orbiting HD 156668 with a minimum mass of four earth masses
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 726:2, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of HD 156668 b, an extrasolar planet with a minimum mass of M-P sin i = 4.15 M-circle plus. This planet was discovered through Keplerian modeling of precise radial velocities from Keck-HIRES and is the second super-Earth to emerge from the NASA-UC Eta-Earth Survey. The best-fit orbit is consistent with circular and has a period of P = 4.6455 days. The Doppler semi-amplitude of this planet, K = 1.89 m s(-1), is among the lowest ever detected, on par with the detection of GJ 581 e using HARPS. A longer period (P approximate to 2.3 years), low-amplitude signal of unknown origin was also detected in the radial velocities and was filtered out of the data while fitting the short-period planet. Additional data are required to determine if the long-period signal is due to a second planet, stellar activity, or another source. Photometric observations using the Automated Photometric Telescopes at Fairborn Observatory show that HD 156668 (an old, quiet K3 dwarf) is photometrically constant over the radial velocity period to 0.1 mmag, supporting the existence of the planet. No transits were detected down to a photometric limit of similar to 3 mmag, ruling out transiting planets dominated by extremely bloated atmospheres, but not precluding a transiting solid/liquid planet with a modest atmosphere.
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| 5. |
- Howard, Andrew W., et al.
(författare)
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THE NASA-UC ETA-EARTH PROGRAM. III. A SUPER-EARTH ORBITING HD 97658 AND A NEPTUNE-MASS PLANET ORBITING G1 785
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 730:1, s. 10-
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of planets orbiting two bright, nearby early K dwarf stars, HD 97658 and G1 785. These planets were detected by Keplerian modeling of radial velocities measured with Keck-HIRES for the NASA-UC Eta-Earth Survey. HD 97658 b is a close-in super-Earth with minimum mass M sin i = 8.2 +/- 1.2 M-circle plus, orbital period P = 9.494 +/- 0.005 days, and an orbit that is consistent with circular. G1 785 b is a Neptune-mass planet with M sin i = 21.6 +/- 2.0 M-circle plus, P = 74.39 +/- 0.12 days, and orbital eccentricity e = 0.30 +/- 0.09. Photometric observations with the T12 0.8 m automatic photometric telescope at Fairborn Observatory show that HD 97658 is photometrically constant at the radial velocity period to 0.09 mmag, supporting the existence of the planet.
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| 6. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 7. |
- Buchhave, Lars A., et al.
(författare)
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An abundance of small exoplanets around stars with a wide range of metallicities
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7403, s. 375-377
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Tidskriftsartikel (refereegranskat)abstract
- The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets(1-4), supporting the model that planets form by accumulation of dust and ice particles(5). Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets(4,6-9). However, how the relationship between size and metallicity extends into the regime of terrestrial-sized exoplanets is unknown. Here we report spectroscopic metallicities of the host stars of 226 small exoplanet candidates discovered by NASA's Kepler mission(10), including objects that are comparable in size to the terrestrial planets in the Solar System. We find that planets with radii less than four Earth radii form around host stars with a wide range of metallicities (but on average a metallicity close to that of the Sun), whereas large planets preferentially form around stars with higher metallicities. This observation suggests that terrestrial planets may be widespread in the disk of the Galaxy, with no special requirement of enhanced metallicity for their formation.
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| 8. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 9. |
- Green, Richard E., et al.
(författare)
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Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
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Tidskriftsartikel (refereegranskat)abstract
- To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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| 10. |
- Jarvis, Erich D., et al.
(författare)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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