| 1. |
- Akimoto, Chizuru, et al.
(author)
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A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
- 2014
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:6, s. 419-424
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Journal article (peer-reviewed)abstract
- Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.
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| 2. |
- Larsson, Bengt, et al.
(author)
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Molecular oxygen in the rho Ophiuchi cloud
- 2007
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 466:3, s. 5-
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Journal article (peer-reviewed)abstract
- Context: Molecular oxygen, O2, has been expected historically to be an abundant component of the chemical species in molecular clouds and, as such, an important coolant of the dense interstellar medium. However, a number of attempts from both ground and from space have failed to detect O2 emission.Aims: The work described here uses heterodyne spectroscopy from space to search for molecular oxygen in the interstellar medium. Methods: The Odin satellite carries a 1.1 m sub-millimeter dish and a dedicated 119 GHz receiver for the ground state line of O2. Starting in 2002, the star forming molecular cloud core ρ Oph A was observed with Odin for 34 days during several observing runs.Results: We detect a spectral line at v_LSR =+3.5 km s-1 with Δ v_FWHM=1.5 km s-1, parameters which are also common to other species associated with ρ Oph A. This feature is identified as the O2 (NJ = 11 - 1_0) transition at 118 750.343 MHz.Conclusions: The abundance of molecular oxygen, relative to H{2} , is 5 × 10-8 averaged over the Odin beam. This abundance is consistently lower than previously reported upper limits.Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Étude Spatiale (CNES). The Swedish Space Corporation has been the industrial prime contractor and also is operating the satellite. Appendix A is only available in electronic form at http://www.aanda.org
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| 3. |
- van Doormaal, Perry T. C., et al.
(author)
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The role of de novo mutations in the development of amyotrophic lateral sclerosis
- 2017
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In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 38:11, s. 1534-1541
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Journal article (peer-reviewed)abstract
- The genetic basis combined with the sporadic occurrence of amyotrophic lateral sclerosis (ALS) suggests a role of de novo mutations in disease pathogenesis. Previous studies provided some evidence for this hypothesis; however, results were conflicting: no genes with recurrent occurring de novo mutations were identified and different pathways were postulated. In this study, we analyzed whole-exome data from 82 new patient-parents trios and combined it with the datasets of all previously published ALS trios (173 trios in total). The per patient de novo rate was not higher than expected based on the general population (P = 0.40). We showed that these mutations are not part of the previously postulated pathways, and gene-gene interaction analysis found no enrichment of interacting genes in this group (P = 0.57). Also, we were able to show that the de novo mutations in ALS patients are located in genes already prone for de novo mutations (P < 1 x 10(-15)). Although the individual effect of rare de novo mutations in specific genes could not be assessed, our results indicate that, in contrast to previous hypothesis, de novo mutations in general do not impose a major burden on ALS risk.
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| 4. |
- Wesson, R., et al.
(author)
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JWST observations of the Ring Nebula (NGC 6720): I. Imaging of the rings, globules, and arcs
- 2024
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In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 528:2, s. 3392-3416
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Journal article (peer-reviewed)abstract
- We present JWST images of the well-known planetary nebula NGC 6720 (the Ring Nebula), covering wavelengths from 1.6 to 25 m. The bright shell is strongly fragmented with some 20 000 dense globules, bright in H2, with a characteristic diameter of 0.2 arcsec and density nH ∼105-106 cm-3. The shell contains a narrow ring of polycyclic aromatic hydrocarbon (PAH) emission. H2 is found throughout the shell and also in the halo. H2 in the halo may be located on the swept-up walls of a biconal polar flow. The central cavity is filled with high-ionization gas and shows two linear structures which we suggest are the edges of a biconal flow, seen in projection against the cavity. The central star is located 2 arcsec from the emission centroid of the cavity and shell. Linear features ('spikes') extend outward from the ring, pointing away from the central star. Hydrodynamical simulations reproduce the clumping and possibly the spikes. Around 10 low-contrast, regularly spaced concentric arc-like features are present; they suggest orbital modulation by a low-mass companion with a period of about 280 yr. A previously known much wider companion is located at a projected separation of about 15 000 au; we show that it is an M2-M4 dwarf. NGC 6720 is therefore a triple star system. These features, including the multiplicity, are similar to those seen in the Southern Ring Nebula (NGC 3132) and may be a common aspect of such nebulae.
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