@article{GrassmannFritscheKeilhaueretal.2012,
  author    = {Grassmann, Felix and Fritsche, Lars G. and Keilhauer, Claudia N. and Heid, Iris M. and Weber, Bernhard H. F.},
  title     = {Modelling the Genetic Risk in Age-Related Macular Degeneration},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {5},
  doi       = {10.1371/journal.pone.0037979},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131315},
  pages     = {e37979},
  year      = {2012},
  abstract  = {Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95\% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95\% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95\% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5\% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2\% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9\% and a specificity of 99.9\% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4\% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2\% of individuals in the two lowest GRS categories which represent almost 50\% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.},
  language  = {en}
}
@article{GassenBrechtefeldSchandryetal.2012,
  author    = {Gassen, Alwine and Brechtefeld, Doris and Schandry, Niklas and Arteaga-Salas, J. Manuel and Israel, Lars and Imhof, Axel and Janzen, Christian J.},
  title     = {DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei},
  series = {Nucleic Acids Research},
  volume    = {40},
  journal   = {Nucleic Acids Research},
  number    = {20},
  doi       = {10.1093/nar/gks801},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131449},
  pages     = {10302 - 10311},
  year      = {2012},
  abstract  = {Cell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. Although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite Trypanosoma brucei, novel regulatory mechanisms seem to have evolved. Here, we analyse the function of the histone methyltransferase DOT1A during cell-cycle progression. Over-expression of DOT1A generates a population of cells with aneuploid nuclei as well as enucleated cells. Detailed analysis shows that DOT1A over-expression causes continuous replication of the nuclear DNA. In contrast, depletion of DOT1A by RNAi abolishes replication but does not prevent karyokinesis. As histone H3K76 methylation has never been associated with replication control in eukaryotes before, we have discovered a novel function of DOT1 enzymes, which might not be unique to trypanosomes.},
  language  = {en}
}