Next-generation profiling to identify the molecular etiology of Parkinson dementia

Adrienne Henderson-Smith, Jason J. Corneveaux, Matthew De Both, Lori Cuyugan, Winnie S. Liang, Matthew Huentelman, Charles Howard Adler, Erika M Driver-Dunckley, Thomas G. Beach, Travis L. Dunckley

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: We sought to determine the underlying cortical gene expression changes associated with Parkinson dementia using a next-generation RNA sequencing approach. Methods: In this study, we used RNA sequencing to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex from neurologically normal control patients, patients with Parkinson disease, and patients with Parkinson disease with dementia. Results: Genes overexpressed in both disease states were involved with an immune response, whereas shared underexpressed genes functioned in signal transduction or as components of the cytoskeleton. Alternative splicing analysis produced a pattern of immune and RNA-processing disturbances. Conclusions: Genes with the greatest degree of differential expression did not overlap with genes exhibiting significant alternative splicing activity. Such variation indicates the importance of broadening expression studies to include exon-level changes because there can be significant differential splicing activity with potential structural consequences, a subtlety that is not detected when examining differential gene expression alone, or is underrepresented with probe-limited array technology.

Original languageEnglish (US)
Article numbere75
JournalNeurology: Genetics
Volume2
Issue number3
DOIs
StatePublished - Jun 1 2016

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Dementia
Alternative Splicing
RNA Sequence Analysis
Gene Expression
Genes
Parkinson Disease
Gyrus Cinguli
Cytoskeleton
Exons
Signal Transduction
Technology

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)

Cite this

Henderson-Smith, A., Corneveaux, J. J., De Both, M., Cuyugan, L., Liang, W. S., Huentelman, M., ... Dunckley, T. L. (2016). Next-generation profiling to identify the molecular etiology of Parkinson dementia. Neurology: Genetics, 2(3), [e75]. https://doi.org/10.1212/NXG.0000000000000075

Next-generation profiling to identify the molecular etiology of Parkinson dementia. / Henderson-Smith, Adrienne; Corneveaux, Jason J.; De Both, Matthew; Cuyugan, Lori; Liang, Winnie S.; Huentelman, Matthew; Adler, Charles Howard; Driver-Dunckley, Erika M; Beach, Thomas G.; Dunckley, Travis L.

In: Neurology: Genetics, Vol. 2, No. 3, e75, 01.06.2016.

Research output: Contribution to journalArticle

Henderson-Smith, A, Corneveaux, JJ, De Both, M, Cuyugan, L, Liang, WS, Huentelman, M, Adler, CH, Driver-Dunckley, EM, Beach, TG & Dunckley, TL 2016, 'Next-generation profiling to identify the molecular etiology of Parkinson dementia', Neurology: Genetics, vol. 2, no. 3, e75. https://doi.org/10.1212/NXG.0000000000000075
Henderson-Smith A, Corneveaux JJ, De Both M, Cuyugan L, Liang WS, Huentelman M et al. Next-generation profiling to identify the molecular etiology of Parkinson dementia. Neurology: Genetics. 2016 Jun 1;2(3). e75. https://doi.org/10.1212/NXG.0000000000000075
Henderson-Smith, Adrienne ; Corneveaux, Jason J. ; De Both, Matthew ; Cuyugan, Lori ; Liang, Winnie S. ; Huentelman, Matthew ; Adler, Charles Howard ; Driver-Dunckley, Erika M ; Beach, Thomas G. ; Dunckley, Travis L. / Next-generation profiling to identify the molecular etiology of Parkinson dementia. In: Neurology: Genetics. 2016 ; Vol. 2, No. 3.
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