Measuring Consequences of Protein Misfolding and Cellular Stress Using OMICS Techniques - Protein Misfolding and Cellular Stress in Disease and Aging - page 120

to find the needles in the haystack. Initiatives like the 1,000
Genomes Project ( 15 ), which will perform full sequencing of
1,000 genomes will provide an important basic catalog of human
genome variation. Personal full genome sequencing will detect
both common and rare variations, whereas genome-wide associa-
tion studies are dependent on the informative quality of common
variants. In the context of misfolding diseases and cellular stress,
one may expect valuable information regarding modulating
genetic factors from full genome sequencing of individuals with
severe phenotypes versus those with mild ones who carry the
same primary mutations in monogenic disease genes.

3.Transcriptomics

Microarray analysis of the transcripts of cells or tissues is cur-
rently the most comprehensive, matured, and also affordable
OMICS technique available. With the knowledge of the sequences
of nearly all genes of humans and model organisms, it is possible
to cover almost all transcripts. Recently, analyses have been fur-
ther refined by the availability of so-called exon-arrays, which
also give information on alternatively spliced transcripts (see,
e.g., ( 16, 17 )). This has further added to the information con-
tent of such analyses. Microarray analysis has been developed
over the years and standardized, and, most importantly, microar-
ray data have been made publicly available in the Gene expres-
sion omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/ ) for
secondary analysis by researchers with similar interests. Great
efforts have been made to ensure that raw and analyzed data are
reported in a standardized manner (MIAME describes the
Minimum Information About a Microarray Experiment) thus giv-
ing the best possibility for researchers to cross-compare and inter-
pret data. Transcriptional changes are very sensitive markers for
gene expression changes; however, transcript levels appear not to
be very good indicators of protein levels ( 18 ).
A transcriptome study in connection with misfolding diseases
was performed by Mandel et al. ( 19 ) to study Parkinson's dis-
ease. RNA samples from substantia nigra from a group of spo-
radic Parkinson's disease patients were compared to controls and
a group of patients with familial Parkinsonism. This study revealed
that similar patterns of transcript changes were observed for the
sporadic and inherited patients, consistent with a convergent
pathogenesis in both groups. The study also identified certain
pathways, both formerly known ones like the proteasomal pro-
tein degradation pathway, whose expression was decreased, as
well as previously unsuspected cellular processes. It could thus

3.1. Microarray
Analysis