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- 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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| 4. |
- Chan, Yang-Hsiang, et al.
(författare)
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Reversible Photoswitching of Spiropyran-Conjugated Semiconducting Polymer Dots
- 2012
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 84:21, s. 9431-9438
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Tidskriftsartikel (refereegranskat)abstract
- Semiconducting polymer dots (Pdots) recently have emerged as a new class of ultrabright fluorescent probes with promising applications in biological detection and imaging. We developed photoswitchable Pdots by conjugating photochromic spiropyran molecules onto poly[9,9-dioctylfluorenyl-2,7-diyl)-co-1,4-benzo-{2,1′-3}-thiadiazole)] (PFBT). The modulation of fluorescence was achieved by ultraviolet irradiation, which converted spiropyran into its visible-absorbing merocyanine form. The merocyanine efficiently quenched the fluorescence of PFBT via Förster resonance energy transfer (FRET). We then reversed the quenching by subsequent irradiation with visible light to get back the fluorescence of PFBT. This FRET-based photomodulation of Pdot fluorescence could be repeated multiple times. We next conjugated biomolecules onto the surface of these photoswitchable Pdots and demonstrated their specific cellular and subcellular labeling to different types of cells without any noticeable nonspecific binding. We anticipate these photoswitchable and biocompatible Pdots will be useful in developing bioimaging techniques in the future.
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| 5. |
- Rong, Yu, et al.
(författare)
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Multicolor Fluorescent Semiconducting Polymer Dots with Narrow Emissions and High Brightness
- 2013
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 7:1, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescent semiconducting polymer dots (Pdots) have attracted great interest because of their superior characteristics as fluorescent probes, such as high fluorescence brightness, fast radiative rates, and excellent photostability. However, currently available Pdots generally exhibit broad emission spectra, which significantly limit their usefulness in many biological applications Involving multiplex detections. Here, we describe the design and development of multicolor narrow emissive Pdots based on different boron dipyrromethene (BODIPY) units. BODIPY-containing semiconducting polymers emitting at multiple wavelengths were synthesized and used as precursors for preparing the Pdots, where intraparticle energy transfer led to highly bright, narrow emissions. The emission full width at half-maximum of the resulting Pdots varies from 40 to 55 nm, which is 15-2 times narrower than those of conventional semiconducting polymer dots. BODIPY 520 Pdots were about an order of magnitude brighter than commercial Qdot 525 under identical laser excitation conditions. Fluorescence imaging and flow cytometry experiments indicate that the narrow emissions from these bright Pdots are promising for multiplexed biological detections.
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| 6. |
- Ye, Fangmao, et al.
(författare)
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Ratiometric temperature sensing with semiconducting polymer dots
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 133:21, s. 8146-8149
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Tidskriftsartikel (refereegranskat)abstract
- This communication describes ultrabright single-nanoparticle ratiometric temperature sensors based on semiconducting polymer dots (Pdots). We attached the temperature sensitive dye—Rhodamine B (RhB), whose emission intensity decreases with increasing temperature—within the matrix of Pdots. The as-prepared Pdot-RhB nanoparticle showed excellent temperature sensitivity and high brightness because it took advantage of the light harvesting and amplified energy transfer capability of Pdots. More importantly, the Pdot-RhB nanoparticle showed ratiometric temperature sensing under a single wavelength excitation and has a linear temperature sensing range that matches well with the physiologically relevant temperatures. We employed Pdot-RhB for measuring intracellular temperatures in a live-cell imaging mode. The exceptional brightness of Pdot-RhB allows this nanoscale temperature sensor to be used also as a fluorescent probe for cellular imaging.
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