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- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Pastorello, A., et al.
(författare)
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SN 2009E : a faint clone of SN 1987A
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537
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Tidskriftsartikel (refereegranskat)abstract
- Context. 1987A-like events form a rare sub-group of hydrogen-rich core-collapse supernovae that are thought to originate from the explosion of blue supergiant stars. Although SN 1987A is the best known supernova, very few objects of this group have been discovered and, hence, studied. Aims. In this paper we investigate the properties of SN 2009E, which exploded in a relatively nearby spiral galaxy (NGC 4141) and that is probably the faintest 1987A-like supernova discovered so far. We also attempt to characterize this subgroup of core-collapse supernovae with the help of the literature and present new data for a few additional objects. Methods. The lack of early-time observations from professional telescopes is compensated by frequent follow-up observations performed by a number of amateur astronomers. This allows us to reconstruct a well-sampled light curve for SN 2009E. Spectroscopic observations which started about 2 months after the supernova explosion, highlight significant differences between SN 2009E and the prototypical SN 1987A. Modelling the data of SN 2009E allows us to constrain the explosion parameters and the properties of the progenitor star, and compare the inferred estimates with those available for the similar SNe 1987A and 1998A. Results. The light curve of SN 2009E is less luminous than that of SN 1987A and the other members of this class, and the maximum light curve peak is reached at a slightly later epoch than in SN 1987A. Late-time photometric observations suggest that SN 2009E ejected about 0.04 M-circle dot of Ni-56, which is the smallest Ni-56 mass in our sample of 1987A-like events. Modelling the observations with a radiation hydrodynamics code, we infer for SN 2009E a kinetic plus thermal energy of about 0.6 foe, an initial radius of similar to 7x10(12) cm and an ejected mass of similar to 19 M-circle dot. The photospheric spectra show a number of narrow (v approximate to 1800 km s(-1)) metal lines, with unusually strong Ba II lines. The nebular spectrum displays narrow emission lines of H, Na I, [Ca II] and [O I], with the [O I] feature being relatively strong compared to the [Ca II] doublet. The overall spectroscopic evolution is reminiscent of that of the faint Ni-56-poor type II-plateau supernovae. This suggests that SN 2009E belongs to the low-luminosity, low Ni-56 mass, low-energy tail in the distribution of the 1987A-like objects in the same manner as SN 1997D and similar events represent the faint tail in the distribution of physical properties for normal type II-plateau supernovae.
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