| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Chen, Daru, et al.
(författare)
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Single-longitudinal-mode erbium-doped fiber laser based on a fiber Bragg grating Fabry-Perot filter
- 2007
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Ingår i: Laser physics. - 1054-660X .- 1555-6611. ; 17:10, s. 1246-1248
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Tidskriftsartikel (refereegranskat)abstract
- A novel single-longitudinal-mode (SLM) erbium-doped fiber laser with a simple linear cavity based on a fiber Bragg grating Fabry-Perot filter (FBG-FPF) and a narrowband (similar to 0.06 nm) FBG is proposed and demonstrated experimentally. Two uniform FBGs form the FBG-FPF, which has two ultranarrow transmission bands with a bandwidth of 0.12 pm and a wavelength spacing of 0.095 nm. By slightly tuning the central wavelength of the narrowband FBG, SLM lasing at 1549.658 or 1549.563 nm (corresponding to the two transmission peaks of the FBG-FPF) is achieved with a laser output power of similar to 4 mW, when the pump power is similar to 75 mW.
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| 4. |
- Feng, Ruizhi, et al.
(författare)
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Mutations in TUBB8 and Human Oocyte Meiotic Arrest.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 374:3, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).
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| 5. |
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| 6. |
- Gao, S., et al.
(författare)
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Microwave frequency up/downconversion based on dual-wavelength fibre laser
- 2009
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Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 45:18, s. 932-933
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Tidskriftsartikel (refereegranskat)abstract
- A novel method of microwave frequency up/downconversion is proposed for microwave/millimetre-wave-based radio-over-fibre (RoF) systems. The uplink and downlink are both based on dual-wavelength single-longitudinal-mode fibre laser modulation and heterodyning, which provides the possibility to realise bidirectional RoF transmissions.
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| 7. |
- Hao, Qian, et al.
(författare)
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Holocene carbon accumulation in lakes of the current east Asian monsoonal margin: Implications under a changing climate
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 737, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Carbon (C) present in lake sediments is an important global sink for CO2; however, an in-depth understanding of the impact of climate variability and the associated changes in vegetation on sediment C dynamics is still lacking. A total of 13 lakes were studied to quantify the influence of climate and vegetation on the reconstructed Holocene C accumulation rate (CAR) in lake sediments of the modern East Asian monsoonal margin. The corresponding paleoclimate information was assessed, including the temperature (30–90°N in the Northern Hemisphere) and precipitation (indicated by the δ18O of the Sanbao, Dongge, and Hulu caves). The Holocene vegetation conditions were inferred by pollen records, including arboreal pollen/non-arboreal pollen and pollen percentages. The results showed that the peak CAR occurred during the mid-Holocene, coinciding with the strongest period of the East Asian summer monsoon and expansion of forests. Lakes in the temperate steppe (TS) regions had a mean CAR of 13.41 ± 0.88 g C m−2 yr−1, which was significantly greater than the CARs of temperate desert (TD) and highland meadow/steppe (HMS; 6.76 ± 0.29 and 7.39 ± 0.73 g C m−2 yr−1, respectively). The major influencing factor for the TS sub-region was vegetation dynamics, especially the proportion of arboreal vegetation, while temperature and vegetation coverage were more important for the HMS. These findings indicate that C accumulation in lake sediments is linked with climate and vegetation changes over long timescales; however, there was notable spatial heterogeneity in the CARs, such as opposing temporal changes and different major influencing factors among the three sub-regions during the mid-Holocene. Aridification and forest loss would decrease C storage. However, prediction of C accumulation remains difficult because of the spatial heterogeneity in CARs and the interaction between the CAR and various factors under future climate change conditions.
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| 8. |
- Li, Furong, et al.
(författare)
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Towards quantification of Holocene anthropogenic land-cover change in temperate China : A review in the light of pollen-based REVEALS reconstructions of regional plant cover
- 2020
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Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 203, s. 1-25
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Forskningsöversikt (refereegranskat)abstract
- In an attempt to quantify Holocene anthropogenic land-cover change in temperate China, we 1) applied the REVEALS model to estimate plant-cover change using 94 pollen records and relative pollen productivity for 27 plant taxa, 2) reviewed earlier interpretation of pollen studies in terms of climate- and human-induced vegetation change, and 3) reviewed information on past land use from archaeological studies. REVEALS achieved a more realistic reconstruction of plant-cover change than pollen percentages in terms of openland versus woodland. The study suggests successive human-induced changes in vegetation cover. The first signs of human-induced land-cover change (crop cultivation, otherwise specified) are found c. 7 ka BP in the temperate deciduous forest, and S and NE Tibetan Plateau (mainly grazing, possibly crop cultivation), 6.5-6 ka BP in the temperate steppe and temperate desert (grazing, uncertain), and 5.5-5 ka BP in the coniferous-deciduous mixed forest, NE subtropical region, and NW Tibetan Plateau (grazing). Further intensification of anthropogenic land-cover change is indicated 5-4.5 ka BP in the E temperate steppe, and S and NE Tibetan Plateau (grazing, cultivation uncertain), 3.5-3 ka BP in S and NE Tibetan Plateau, W temperate steppe, temperate desert (grazing), and NW Tibetan Plateau (probably grazing), and 2.5-2 ka BP in the temperate deciduous forest, N subtropical region, and temperate desert (grazing). These changes generally agree with increased human activity as documented by archaeological studies. REVEALS reconstructions have a stronger potential than biomization to evaluate scenarios of anthropogenic land-cover change such as HYDE, given they are combined with information from archaeological studies.
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| 9. |
- Ma, Zhuo, et al.
(författare)
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Deciphering early human pancreas development at the single-cell level
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity. Here, the authors revealed molecular heterogeneity, developmental trajectory and regulatory network of early human pancreas development, and depict the whole progression of pancreatic organogenesis during the first trimester at the single-cell level.
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| 10. |
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