DNA methylome study of human cerebellar tissues identified genes and pathways possibly involved in essential tremor
Open Access
- 8 December 2019
- journal article
- research article
- Published by Oxford University Press (OUP) in Precision Clinical Medicine
- Vol. 2 (4), 221-234
- https://doi.org/10.1093/pcmedi/pbz028
Abstract
Essential tremor (ET) is a neurological syndrome of unknown origin with poorly understood etiology and pathogenesis. It is suggested that the cerebellum and its tracts may be involved in the pathophysiology of ET. DNA methylome interrogation of cerebellar tissue may help shine some light on the understanding of the mechanism of the development of ET. Our study used postmortem human cerebellum tissue samples collected from 12 ET patients and 11 matched non-ET controls for DNA methylome study to identify differentially methylated genes in ET. Using Nugen’s Ovation reduced representation bisulfite sequencing (RRBS), we identified 753 genes encompassing 938 CpG sites with significant differences in DNA methylation between the ET and the control group. Identified genes were further analyzed with Ingenuity Pathway Analysis (IPA) by which we identified certain significant pathways, upstream regulators, diseases and functions, and networks associated with ET. Our study provides evidence that there are significant differences in DNA methylation patterns between the ET and control samples, suggesting that the methylation alteration of certain genes in the cerebellum may be associated with ET pathogenesis. The identified genes allude to the GABAergic hypothesis which supports the notation that ET is a neurodegenerative disease, particularly involving the cerebellum.Keywords
Funding Information
- National Institutes of Health (S10OD019960)
- National Institute of Neurological Disorders and Stroke (U24 NS072026)
- National Institute on Aging (P30 AG19610)
- Arizona Department of Health Services (211002)
- Arizona Biomedical Research Commission (4001, 1001, 0011, 05-901)
- Michael J. Fox Foundation for Parkinson's Research
- Ardmore Institute of Health (2150141)
This publication has 40 references indexed in Scilit:
- The Pathophysiology of Essential Tremor and Parkinson’s TremorCurrent Neurology and Neuroscience Reports, 2013
- Predicting Age of Onset in Familial Essential Tremor: How Much Does Age of Onset Run in FamiliesNeuroepidemiology, 2013
- Essential Tremor is Not a Neurodegenerative DiseaseNeurodegenerative Disease Management, 2012
- methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profilesGenome Biology, 2012
- Quantitative gait analysis in essential tremor reveals impairments that are maintained into advanced ageGait & Posture, 2011
- Estimating annual rate of decline: prospective, longitudinal data on arm tremor severity in two groups of essential tremor casesJournal of Neurology, Neurosurgery & Psychiatry, 2011
- Purkinje cell survival in organotypic cultures: Implication of Rho and its downstream effector ROCKJournal of Neuroscience Research, 2007
- Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formationProceedings of the National Academy of Sciences, 2006
- Red nuclear and cerebellar but no olivary activation associated with essential tremor: A positron emission tomoraphic studyAnnals of Neurology, 1994
- Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.The Journal of cell biology, 1991