Diversity of human clock genotypes and consequences

Abstract

The molecular clock consists of a number of genes that form transcriptional and posttranscriptional feedback loops, which function together to generate circadian oscillations that give rise to circadian rhythms of our behavioral and physiological processes. Genetic variations in these clock genes have been shown to be associated with phenotypic effects in a repertoire of biological processes, such as diurnal preference, sleep, metabolism, mood regulation, addiction, and fertility. Consistently, rodent models carrying mutations in clock genes also demonstrate similar phenotypes. Taken together, these studies suggest that human clock-gene variants contribute to the phenotypic differences observed in various behavioral and physiological processes, although to validate this requires further characterization of the molecular consequences of these polymorphisms. Investigating the diversity of human genotypes and the phenotypic effects of these genetic variations shall advance our understanding of the function of the circadian clock and how we can employ the clock to improve our overall health.

Keywords: Human circadian clock; Human sleep behaviors; Human sleep duration.

Figure 3.1

Free-running period of sleep/wake and body temperature cycles in a FASP subject. Sleep/wake (A) and body temperature (B) rhythms of a 69-year-old female monitored in time isolation for 18 days. The data are double plotted. (A) Filled bars indicate periods of sleep derived from polygraphically-recorded sleep scored using “standard” criteria. (B) Filled bars indicate periods when body temperature is below the daily mean. The free-running period of both variables are 23.3 h based on chi-squared periodogram. Adapted from Ref. 73.

Figure 3.2

Activity recording of a DEC2-P384R mutatiocarrier. Filled bars indicate periods of activity by wrist actigraphy. Extended periods of activity can be observed. Adapted from Ref. 125.