Central and peripheral circadian clock genes, their statistical analysis for rhythms, and relationship to health and disease

Robert B. Sothern, T. Yamamoto, Germaine G Cornelissen-Guillaume, T. Takumi, F. Halberg

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Molecular clocks present in organs and individual cells throughout the body are central for the temporal coordination of rhythms in internal biological processes among themselves and with external environmental cycles; altered function of specific clock gene (CG) components can have significant impact relevant to health and disease. We herein review current knowledge pertaining to the presence and robustness of circadian rhythms in CGs in the suprachiasmatic nucleus and peripheral organs, and the importance of CGs to general health and the diagnosis and treatment of human disorders and disease. Also discussed are developmental aspects of rhythms in some CGs and tissues, time of day vs. circadian stage, using synchronized vs. constant conditions to monitor a rhythm, and subjective vs. objective interpretations of rhythms. To emphasize the latter, chronobiological statistics (ANOVA, single cosinor) are applied to published circadian CG mRNA expression data (which had been described subjectively) as an example of objectively determining rhythm probability and obtaining estimates for circadian amplitudes and acrophases. The data base consisted of 14 CGs (mPer1,2,3, mCry1,2, mBmal1, mC/C/1δ,ε, mClock, mDbp, mNpas2, mRev-erbα,β, mTim) in each of 7 mouse organs harvested every 4h for 24h from male Balb/c mice on day 3 in continuous darkness. Excluding the usually non-24h-rhythmic testis and CG mTim, rhythms significant at p≤0.05 were found in 81% (63/78) of CGs and when including borderline significant at p≤0.10, in 97% (76/78) of CGs. A statistically-determined circadian amplitude and acrophase for each CG in each tissue can be useful in making objective comparisons of rhythm parameters in CGs between various peripheral organs, species, and/or studies of different conditions (e.g., photoperiods, feeding schedules, aging, disease). Use of these parameters adds new endpoints for diagnoses and approaches for therapeutic interventions in conditions where disturbance of circadian CG expression is an important cause of morbidity associated with chronic illnesses and diseases with a strong circadian component, including cardiovascular disease, epilepsy, cancer, metabolic syndrome, and sleep-related disorders, among others, also reviewed herein.

Original languageEnglish (US)
Pages (from-to)133-163
Number of pages31
JournalScripta Medica Facultatis Medicae Universitatis Brunensis Masarykianae
Volume82
Issue number3
StatePublished - Oct 26 2009

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Circadian Clocks
Health
Chronic Disease
Genes
Gene Components
Biological Phenomena
Gene Expression
Suprachiasmatic Nucleus
Darkness
Photoperiod
Circadian Rhythm
Testis
Epilepsy
Analysis of Variance
Appointments and Schedules
Cardiovascular Diseases
Databases
Morbidity
Messenger RNA
Neoplasms

Keywords

  • Circadian
  • Clock gene
  • Cosinor
  • Peripheral organs
  • Rhythm

Cite this

Central and peripheral circadian clock genes, their statistical analysis for rhythms, and relationship to health and disease. / Sothern, Robert B.; Yamamoto, T.; Cornelissen-Guillaume, Germaine G; Takumi, T.; Halberg, F.

In: Scripta Medica Facultatis Medicae Universitatis Brunensis Masarykianae, Vol. 82, No. 3, 26.10.2009, p. 133-163.

Research output: Contribution to journalReview article

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