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Supplemental Web Site for
Expression Profiling Reveals
Altered Satellite Cell Numbers and Glycolytic Enzyme Transcription
in Nemaline Myopathy Muscle.
Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg
SA, Lidov HGW, Kohane IS, Kunkel LM, Beggs AH. PNAS
2003; 100(8):4666-4671.
PMID:
12677001 [PubMed - indexed for MEDLINE]
Genetics Division and Genomics Program, Neurology Department,
Children's Hospital Boston and Harvard Medical School, Boston,
MA, 02115, USA.
Abstract
The nemaline myopathies (NMs) are a clinically and genetically
heterogeneous group of disorders characterized by nemaline
rods and skeletal muscle weakness. Mutations in five sarcomeric
thin filament genes have been identified. However, the molecular
consequences of these mutations are unknown. Using Affymetrix
oligonucleotide microarrays, we have analyzed the expression
patterns of >21,000 genes and expressed sequence tags in
skeletal muscles of 12 NM patients and 21 controls.
Multiple complementary approaches were used for data analysis,
including geometric fold analysis, two-tailed unequal variance
t test, hierarchical clustering, relevance network, and nearest-neighbor
analysis. We report the identification of high satellite cell
populations in NM and the significant down-regulation of transcripts
for key enzymes of glucose and glycogen metabolism as well
as a possible regulator of fatty acid metabolism, UCP3. Interestingly,
transcript level changes of multiple genes suggest possible
changes in Ca2+ homeostasis. The increased expression of multiple
structural proteins was consistent with increased fibrosis.
This comprehensive study of downstream molecular consequences
of NM gene mutations provides insights in the cellular events
leading to the NM phenotype.
Nearest Neighbors
Nearest neighbors: Nearest neighbor analysis of 206 reliably
changed probe sets against the 25,115 U95Av2 and U95B probe
sets, across 34 NM and normal skeletal muscle specimens. For
each of the 206 probe sets the 50 nearest neighbors with a
proximity of at least 0.6 (using correlation coefficient as
dissimilarity measure) are presented. The unnormalized expression
values for each nearest neighbor are also available. Links
provide the correlation coefficient graph for each pairwise
comparison. More information regarding all probe sets can
be obtained at http://www.affymetrix.com
Browse
nearest neighbors data
Supplemental Data
Supplemental
Tables
The following Supporting Information is available for this
article:
Table
1
Supporting
Text
Table
2
Table
3
Table
4
Supplemental
Figures
RelNet
1
RelNet
2
Figure
5
Figure 5: Relevance network from analysis of 206 reliably
changed probe sets indicates coordinate regulation of glycolytic
enzyme and other transcripts in NM muscles. The largest relevance
network (no. 17) generated by the analysis of 13 NM samples
at correlation coefficient cutoff ©¯80% consists
of 36 probe sets (Upper). Each box represents a probe set
and indicates the gene name (or GenBank accession number).
Probe sets representative of molecular pathways of particular
interest are highlighted according to the color key on the
upper left corner. Lines connect probe sets with expression
patterns correlating by >80%. Increased line thickness
indicates higher correlation, and red indicates negative correlation.
(Lower) The equivalent relevance networks from the analysis
of 21 normal samples.
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