Real time PCR.

<p>Real time PCR analysis of selected gene expression. All the pathological samples display alterations consistent with the gene chip expression level. Changes in transcript abundance are expressed as log2 ratio to control mean.</p

Multidimensional scaling of expression data.

<p>MDS of the expression profiles of ALS and controls shows the correct segregation of samples (see text for details). ALS samples are represented by spheres and controls by cubes.</p

Mitochondrial Network Genes in the Skeletal Muscle of Amyotrophic Lateral Sclerosis Patients

<div><p>Recent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal muscle, using microarray technology and gene regulatory network analysis. The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls. The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals. In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism. Overall, the analytical approach used in this study offer the possibility to observe higher levels of correlation (i.e. common expression trends) among genes, whose function seems to be aberrantly activated during the progression of muscle atrophy.</p> </div

Expression levels of single genes across samples.

<p>Co-regulation of functionally related genes: (A–F) members of complement system, (G–H) co-regulated and selective induction in T2-STIR + FSHD muscles can be observed for SFRP1 and its receptor FZD4 and (I–L) for adipose tissue genes and inflammatory adipokines.</p

Summary table of FSHD samples.

<p>+  =  mild increase, ++  =  moderate increase, +++  =  marked increase. * samples from the same patient.</p

Experimental design.

<p>The flowchart schematizes the experimental steps of the statistical analysis of microarray data.</p

Unsupervised hierarchical clustering of the validation experiment.

<p>Unsupervised hierarchical clustering of the validation experiment.</p

Functional categories and genes modulated in T2-STIR + FSHD with respect to IM.

<p>All of the cited genes were expressed to a higher extent in T2-STIR + FSHD muscles.</p

Differentially expressed genes list.

1<p>Ages of patients and controls are not significantly different (p: 0.2648).</p>2<p>Time from symptom onset to muscle biopsy.</p

DAVID functional analysis.

<p>DAVID functional analysis.</p