Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle

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

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

The primary cause of Duchenne muscular dystrophy (DMD) is a mutation in the dystrophin gene leading to the absence of the corresponding RNA transcript and protein. Absence of dystrophin leads to disruption of the dystrophin-associated protein complex and substantial changes in skeletal muscle pathology. Although the histological pathology of dystrophic tissue has been well documented, the underlying molecular pathways remain poorly understood. To examine the pathogenic pathways and identify new or modifying factors involved in muscular dystrophy, expression microarrays were used to compare individual gene expression profiles of skeletal muscle biopsies from 12 DMD patients and 12 unaffected control patients. Two separate statistical analysis methods 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 105 genes that differ significantly in expression level between unaffected and DMD muscle. Many of the differentially expressed genes reflect changes in histological pathology. For instance, immune response signals and extracellular matrix genes are overexpressed in DMD muscle, an indication of the infiltration of inflammatory cells and connective tissue. Significantly more genes are overexpressed than are underexpressed in dystrophic muscle, with dystrophin underexpressed, whereas other genes encoding muscle structure and regeneration processes are overexpressed, reflecting the regenerative nature of the disease.

Original languageEnglish
Pages (from-to)15000-15005
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number23
DOIs
Publication statusPublished - 12 Nov 2002
Externally publishedYes

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Duchenne Muscular Dystrophy
Skeletal Muscle
Biopsy
Gene Expression
Dystrophin
Genes
Muscles
Pathology
Dystrophin-Associated Protein Complex
Connective Tissue Cells
Muscular Dystrophies
Transcriptome
Extracellular Matrix
Regeneration
RNA
Mutation
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. / Haslett, Judith N.; Sanoudou, Despina; Kho, Alvin T.; Bennett, Richard R.; Greenberg, Steven A.; Kohane, Isaac S.; Beggs, Alan H.; Kunkel, Louis M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 23, 12.11.2002, p. 15000-15005.

Research output: Contribution to journalArticle

Haslett, Judith N. ; Sanoudou, Despina ; Kho, Alvin T. ; Bennett, Richard R. ; Greenberg, Steven A. ; Kohane, Isaac S. ; Beggs, Alan H. ; Kunkel, Louis M. / Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 23. pp. 15000-15005.
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