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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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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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- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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- Gemmell, Neil J., et al.
(författare)
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The tuatara genome reveals ancient features of amniote evolution
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 584:7821, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- The tuatara (Sphenodon punctatus)—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2—is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes2,4. Here we analyse the genome of the tuatara, which—at approximately 5 Gb—is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.
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- Kallitsis, Evangelos, et al.
(författare)
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Think global act local: The dependency of global lithium-ion battery emissions on production location and material sources
- 2024
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Ingår i: Journal of Cleaner Production. - 0959-6526. ; 449
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Tidskriftsartikel (refereegranskat)abstract
- The pursuit of low-carbon transport has significantly increased demand for lithium-ion batteries. However, the rapid increase in battery manufacturing, without adequate consideration of the carbon emissions associated with their production and material demands, poses the threat of shifting the bulk of emissions upstream. In this article, a life cycle assessment (LCA) model is developed to account for the cradle-to-gate carbon footprint of lithium-ion batteries across 26 Chinese provinces, 20 North American locations and 19 countries in Europe and Asia. Analysis of published LCA data reveals significant uncertainty associated with the carbon emissions of key battery materials; their overall contribution to the carbon footprint of a LIB varies by a factor of ca. 4 depending on production route and source. The links between production location and the gate-to-gate carbon footprint of battery manufacturing are explored, with predicted median values ranging between 0.1 and 69.5 kg CO2-eq kWh−1. Leading western-world battery manufacturing locations in the US and Europe, such as Kentucky and Poland are found to have comparable carbon emissions to Chinese rivals, even exceeding the carbon emissions of battery manufacturing in several Chinese provinces. Such resolution on material and energy contributions to the carbon footprint of LIBs is essential to inform policy- and decision-making to minimise the carbon emissions of the battery value chain. Given the current status quo, the global carbon footprint of the lithium-ion battery industry is projected to reach up to 1.0 Gt CO2-eq per year within the next decade. With material supply chain decarbonisation and energy savings in battery manufacturing, a lower estimate of 0.5 Gt CO2-eq per year is possible.
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