| 11. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 12. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 13. |
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| 14. |
- Segal-Raz, Hava, et al.
(författare)
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ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
- 2011
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Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 12:7, s. 713-719
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Tidskriftsartikel (refereegranskat)abstract
- The cellular response to double-strand breaks (DSBs) in DNA is a complex signalling network, mobilized by the nuclear protein kinase ataxia-telangiectasia mutated (ATM), which phosphorylates many factors in the various branches of this network. A main question is how ATM regulates DSB repair. Here, we identify the DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) as an ATM target. PNKP phosphorylates 5'-OH and dephosphorylates 3'-phosphate DNA ends that are formed at DSB termini caused by DNA-damaging agents, thereby regenerating legitimate ends for further processing. We establish that the ATM phosphorylation targets on human PNKP-Ser 114 and Ser 126-are crucial for cellular survival following DSB induction and for effective DSB repair, being essential for damage-induced enhancement of the activity of PNKP and its proper accumulation at the sites of DNA damage. These findings show a direct functional link between ATM and the DSB-repair machinery.
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| 15. |
- Yang Lin, Shih, 1979-, et al.
(författare)
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Poster : Adaptive Wavelength Adjustment (AWLA) for Cooperative Speed Harmonization
- 2014
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Ingår i: 2014 IEEE Vehicular Networking Conference (VNC). - Piscataway, NJ : IEEE Press. - 9781479976607 ; , s. 113-114, s. 113-114
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Konferensbidrag (refereegranskat)abstract
- Traffic merge on express-ways creates bottlenecks for traffic flow that potentially lead to traffic jams, especially in dense traffic. Cooperative speed harmonization (CSH), where vehicles are grouped and associated to virtual speed waves for group-wise joining at intersections, is proven to be efficient for on-ramp traffic merge. Based on CSH and considering variations of traffic density from joining roads, an adaptive wavelength adjustment (AWLA) mechanism is proposed in this paper. AWLA extends CSH by dynamically adjusting the length of segments in virtual waves according to the traffic densities of the joining roads. Therefore, roads with denser traffic may have larger segments to carry more vehicles through the intersection, which may improve the overall performance. Simulation results have shown that AWLA can achieve lower CO2 emissions and shorter travel time compared to CSH with static segment settings.
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| 16. |
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| 17. |
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