Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis

Claudia Figueroa-Romero, Junguk Hur, Diane E. Bender, Colin E. Delaney, Michael D. Cataldo, Andrea L. Smith, Raymond Yung, Douglas M. Ruden, Brian C. Callaghan, Eva L. Feldman

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a terminal disease involving the progressive degeneration of motor neurons within the motor cortex, brainstem and spinal cord. Most cases are sporadic (sALS) with unknown causes suggesting that the etiology of sALS may not be limited to the genotype of patients, but may be influenced by exposure to environmental factors. Alterations in epigenetic modifications are likely to play a role in disease onset and progression in ALS, as aberrant epigenetic patterns may be acquired throughout life. The aim of this study was to identify epigenetic marks associated with sALS. We hypothesize that epigenetic modifications may alter the expression of pathogenesis-related genes leading to the onset and progression of sALS. Using ELISA assays, we observed alterations in global methylation (5 mC) and hydroxymethylation (5 HmC) in postmortem sALS spinal cord but not in whole blood. Loci-specific differentially methylated and expressed genes in sALS spinal cord were identified by genome-wide 5mC and expression profiling using high-throughput microarrays. Concordant direction, hyper- or hypo-5mC with parallel changes in gene expression (under- or over-expression), was observed in 112 genes highly associated with biological functions related to immune and inflammation response. Furthermore, literature-based analysis identified potential associations among the epigenes. Integration of methylomics and transcriptomics data successfully revealed methylation changes in sALS spinal cord. This study represents an initial identification of epigenetic regulatory mechanisms in sALS which may improve our understanding of sALS pathogenesis for the identification of biomarkers and new therapeutic targets.

Original languageEnglish (US)
Article numbere52672
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 29 2012

Fingerprint

Epigenomics
epigenetics
spinal cord
Genes
Spinal Cord
Methylation
Amyotrophic Lateral Sclerosis
genes
methylation
pathogenesis
Biomarkers
Microarrays
Gene expression
Neurons
Environmental Exposure
Motor Cortex
Motor Neurons
brain stem
Assays
motor neurons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Figueroa-Romero, C., Hur, J., Bender, D. E., Delaney, C. E., Cataldo, M. D., Smith, A. L., ... Feldman, E. L. (2012). Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis. PloS one, 7(12), [e52672]. https://doi.org/10.1371/journal.pone.0052672

Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis. / Figueroa-Romero, Claudia; Hur, Junguk; Bender, Diane E.; Delaney, Colin E.; Cataldo, Michael D.; Smith, Andrea L.; Yung, Raymond; Ruden, Douglas M.; Callaghan, Brian C.; Feldman, Eva L.

In: PloS one, Vol. 7, No. 12, e52672, 29.12.2012.

Research output: Contribution to journalArticle

Figueroa-Romero, C, Hur, J, Bender, DE, Delaney, CE, Cataldo, MD, Smith, AL, Yung, R, Ruden, DM, Callaghan, BC & Feldman, EL 2012, 'Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis', PloS one, vol. 7, no. 12, e52672. https://doi.org/10.1371/journal.pone.0052672
Figueroa-Romero C, Hur J, Bender DE, Delaney CE, Cataldo MD, Smith AL et al. Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis. PloS one. 2012 Dec 29;7(12). e52672. https://doi.org/10.1371/journal.pone.0052672
Figueroa-Romero, Claudia ; Hur, Junguk ; Bender, Diane E. ; Delaney, Colin E. ; Cataldo, Michael D. ; Smith, Andrea L. ; Yung, Raymond ; Ruden, Douglas M. ; Callaghan, Brian C. ; Feldman, Eva L. / Identification of Epigenetically Altered Genes in Sporadic Amyotrophic Lateral Sclerosis. In: PloS one. 2012 ; Vol. 7, No. 12.
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