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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Sun, Q., et al.
(författare)
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Prevalence and cardiovascular risk factors of asymptomatic intracranial arterial stenosis : the Kongcun Town Study in Shandong, China
- 2020
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 27:4, s. 729-735
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose This study was to investigate the prevalence and cardiovascular risk factors (CRFs) of asymptomatic intracranial atherosclerotic stenosis (aICAS) amongst middle-aged and older adults living in rural communities in China. Methods This population-based study included 2019 subjects (aged >= 40 years, 52.3% women) who were free of stroke and living in rural communities in China. From October 2017 to May 2018, data on demographics, CRFs and health conditions were collected through face-to-face interviews, physical examination and laboratory tests. Asymptomatic ICAS was detected through a two-phase procedure: a screening phase with transcranial Doppler ultrasound, followed by a diagnostic phase with magnetic resonance angiography examination. Multivariable logistic regression models were used to analyse CRFs associated with aICAS. Results Of the 2019 participants, aICAS was detected in 153 persons. The overall prevalence of aICAS was 7.6%, and the prevalence of moderate-to-severe aICAS was 5.0%. The multi-adjusted odds ratio (95% confidence interval) of aICAS associated with CRFs was 2.40 (1.56-3.69) for hypertension, 1.91 (1.32-2.76) for high hypersensitive C-reactive protein, 1.68 (1.14-2.49) for diabetes and 1.61 (1.08-2.41) for overweight or obesity. When these four CRFs were aggregated, compared with participants without any of these factors, the multi-adjusted odds ratios (95% confidence interval) of aICAS for persons concurrently having one, two and three or more of these factors were 1.14 (0.52-2.48), 2.91 (1.42-5.99) and 5.51 (2.64-11.50), respectively (P for linear trend <0.001). Conclusions Asymptomatic ICAS is common amongst rural-dwelling middle-aged and older Chinese people. Hypertension, diabetes, overweight or obesity and high hypersensitive C-reactive protein, especially when coexisting, are strongly associated with aICAS.
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- Wortman, J. R., et al.
(författare)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Tidskriftsartikel (refereegranskat)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 8. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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- Zhou, Y., et al.
(författare)
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Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity
- 2015
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 287:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. (C) 2015 Elsevier Inc. All rights reserved.
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