12 research outputs found
Friedrich Gottlieb Welckers Einleitung zu Vorträgen über die deutsche Geschichte (1815) : neu herausgegeben und erläutert von robert Fritzsche Dr. phil.
Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington’s disease
Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington’s disease
Top-Down Proteomics and Direct Surface Sampling of Neonatal Dried Blood Spots: Diagnosis of Unknown Hemoglobin Variants
MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies
The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset
Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) =11.13, P =2 × 10 -5] and in the HD MAPS cohort [F(2, 688) =38.27, P = 2 × 10 -16]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range. © 2006 The Authors Journal compilation © 2006 University College London.link_to_subscribed_fulltex