Gene expression profiling of Duchenne muscular dystrophy skeletal muscle

Judith N. Haslett, Despina Sanoudou, Alvin T. Kho, Mei Han, Richard R. Bennett, Isaac S. Kohane, Alan H. Beggs, Louis M. Kunkel

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The primary cause of Duchenne muscular dystrophy (DMD) is a mutation in the dystrophin gene, leading to absence of the corresponding protein, disruption of the dystrophin-associated protein complex, and substantial changes in skeletal muscle pathology. Although the primary defect is known and the histological pathology well documented, the underlying molecular pathways remain in question. To clarify these pathways, we used expression microarrays to compare individual gene expression profiles for skeletal muscle biopsies from DMD patients and unaffected controls. We have previously published expression data for the 12,500 known genes and full-length expressed sequence tags (ESTs) on the Affymetrix HG-U95Av2 chips. Here we present comparative expression analysis of the 50,000 EST clusters represented on the remainder of the Affymetrix HG-U95 set. Individual expression profiles were generated for biopsies from 10 DMD patients and 10 unaffected control patients. Two methods of statistical analysis were used to interpret the resulting data (t-test analysis to determine the statistical significance of differential expression and geometric fold change analysis to determine the extent of differential expression). These analyses identified 183 probe sets (59 of which represent known genes) that differ significantly in expression level between unaffected and disease muscle. This study adds to our knowledge of the molecular pathways that are altered in the dystrophic state. In particular, it suggests that signaling pathways might be substantially involved in the disease process. It also highlights a large number of unknown genes whose expression is altered and whose identity therefore becomes important in understanding the pathogenesis of muscular dystrophy.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalNeurogenetics
Volume4
Issue number4
DOIs
Publication statusPublished - 1 Aug 2003
Externally publishedYes

Fingerprint

Duchenne Muscular Dystrophy
Gene Expression Profiling
Skeletal Muscle
Expressed Sequence Tags
Dystrophin-Associated Protein Complex
Pathology
Genes
Biopsy
Dystrophin
Muscular Dystrophies
Transcriptome
Gene Expression
Muscles
Mutation
Proteins

Keywords

  • Duchenne muscular dystrophy
  • Expression oligonucleotide microarrays
  • Pathogenesis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

Haslett, J. N., Sanoudou, D., Kho, A. T., Han, M., Bennett, R. R., Kohane, I. S., ... Kunkel, L. M. (2003). Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. Neurogenetics, 4(4), 163-171. https://doi.org/10.1007/s10048-003-0148-x

Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. / Haslett, Judith N.; Sanoudou, Despina; Kho, Alvin T.; Han, Mei; Bennett, Richard R.; Kohane, Isaac S.; Beggs, Alan H.; Kunkel, Louis M.

In: Neurogenetics, Vol. 4, No. 4, 01.08.2003, p. 163-171.

Research output: Contribution to journalArticle

Haslett, JN, Sanoudou, D, Kho, AT, Han, M, Bennett, RR, Kohane, IS, Beggs, AH & Kunkel, LM 2003, 'Gene expression profiling of Duchenne muscular dystrophy skeletal muscle', Neurogenetics, vol. 4, no. 4, pp. 163-171. https://doi.org/10.1007/s10048-003-0148-x
Haslett JN, Sanoudou D, Kho AT, Han M, Bennett RR, Kohane IS et al. Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. Neurogenetics. 2003 Aug 1;4(4):163-171. https://doi.org/10.1007/s10048-003-0148-x
Haslett, Judith N. ; Sanoudou, Despina ; Kho, Alvin T. ; Han, Mei ; Bennett, Richard R. ; Kohane, Isaac S. ; Beggs, Alan H. ; Kunkel, Louis M. / Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. In: Neurogenetics. 2003 ; Vol. 4, No. 4. pp. 163-171.
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