This emphasizes the importance of hybridizing all samples together when microarrays are used to look for biological differences in the large-scale organization of gene expression levels.
We use data from the MicroArray Quality Control Project (MAQC) to demonstrate that our method is robust and that it reliably detects biological differences in the large-scale organization of gene expression levels.
Despite the presence of effects of hybridization, we also showed using the MAQC data set that biologically related differences in the large-scale organization of gene expression levels are consistently and reproducibly detected.
We found in multiple microarray experiments that differences in the large-scale organization of gene expression levels in the hippocampus, rather than specific differences in gene expression levels, were associated with individual variability in hippocampus-related behaviors.
Similarly we found even in the presence of technical effects of RNA processing method that biologically related differences in the large-scale organization of gene expression levels associated with postnatal handling were detected using either method of RNA processing.
Because the authors examined gene expression in both the hippocampus and the amygdala, we were also able to address the question of regional specificity of differences in the large-scale organization of gene expression levels that are associated with behavioral variability.
In order to quantify possible cumulative differences in the large-scale organisation of the heterochromatin of chromosome 1 in ICF B-cells and controls, we measured the intra-nuclear areas occupied by the juxtacentromeric heterochromatic regions, as defined by hybridisation on 2D-fixed interphase nuclei with the corresponding classical satellite DNA probe (Fig. 2).
The use of behaviorally naïve mice rules out the possibility that was not addressed in our experiments that effects of behavioral testing on levels of gene expression might account for differences in the large-scale organization of gene expression levels that we found between groups.
Using the Microarray Quality Control (MAQC) data set, we demonstrated that our method reliably detects biologically mediated differences in the large-scale organization of gene expression levels, but that it is also sensitive to technical factors such as hybridization batch and RNA processing method.
Having established the existence of consistent and quantifiable differences in the large-scale organisation of the juxtacentromeric heterochromatin in ICF, we proceeded to investigate possible changes in the intranuclear positioning of this genomic region in this syndrome, using as a spatial reference the extreme periphery.
The asymmetry shown by the position of the barycenter reveals a north south hemispheric difference in the large-scale ionospheric variations and provides evidence for NSA based on geomagnetic coordinates.
