Molecular Characterization of Human Sleep Variants

Sleep disruption and duration has been shown to have significant impact on human health, quality of life, and life expectancy. Among humans, it is clear that the biological need for sleep varies dramatically. Natural short sleepers have a lifelong tendency to sleep only 4–5 hours per night and to awaken refreshed and energetic. Natural long sleepers biologically require 9–10 hours/night to feel well rested. The reason for these differences is not known and no genetic forms of either phenotype have been described. In contrast to sleep (where almost nothing is known), there is a wealth of information on the genetics of clock function across species. Sleep and circadian function are distinct processes that interact in living organisms. Although these two systems can operate independently, recent studies indicate a more intimate relationship. In addition to two familial advanced sleep phase syndrome mutations, we have identified a mutation which leads to a short sleep requirement phenotype in human. This represents a new possibility for us to begin probing the mechanisms of human sleep homeostasis. Understanding of human sleep regulation mechanism has the potential to produce an enormous impact on our understanding of many biological pathways including brain functions (vigilance, memory, executive function, math processing, cognitive speed, and spatial orientation), behavior, health, and longevity.