title: Genetic insights on sleep schedules: this time, it's PERsonal.
abstract: The study of circadian rhythms is emerging as a fruitful opportunity for understanding cellular mechanisms that govern human physiology and behavior, fueled by evidence directly linking sleep disorders to genetic mutations affecting circadian molecular pathways. Familial advanced sleep-phase disorder (FASPD) is the first recognized Mendelian circadian rhythm trait, and affected individuals exhibit exceptionally early sleep-wake onset due to altered post-translational regulation of period homolog 2 (PER2). Behavioral and cellular circadian rhythms are analogously affected because the circadian period length of behavior is reduced in the absence of environmental time cues, and cycle duration of the molecular clock is likewise shortened. In light of these findings, we review the PER2 dynamics in the context of circadian regulation to reveal the mechanism of sleep-schedule modulation. Understanding PER2 regulation and functionality may shed new light on how our genetic composition can influence our sleep-wake behaviors.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: S Y Christin
authors.initials: SY
authors.lastname: Chong
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ptáček
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Fu
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*; D014851:Wakefulness / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C539040:PER protein, Drosophila; C421902:PER2 protein, human; D056950:Period Circadian Proteins