Genetic analysis of sleep

Abstract

Almost 20 years ago, the gene underlying fatal familial insomnia was discovered, and first suggested the concept that a single gene can regulate sleep. In the two decades since, there have been many advances in the field of behavioral genetics, but it is only in the past 10 years that the genetic analysis of sleep has emerged as an important discipline. Major findings include the discovery of a single gene underlying the sleep disorder narcolepsy, and identification of loci that make quantitative contributions to sleep characteristics. The sleep field has also expanded its focus from mammalian model organisms to Drosophila, zebrafish, and worms, which is allowing the application of novel genetic approaches. Researchers have undertaken large-scale screens to identify new genes that regulate sleep, and are also probing questions of sleep circuitry and sleep function on a molecular level. As genetic tools continue to be refined in each model organism, the genes that support a specific function in sleep will become more apparent. Thus, while our understanding of sleep still remains rudimentary, rapid progress is expected from these recently initiated studies.

Figure 1.

Brain regions in the fly important for sleep–wake regulation. Many of the major neurotransmitter systems within the fly have been analyzed for their role in sleep. In the biogenic amine category, only octopamine has been localized to a specific cell group relevant for its role in sleep–wake behavior (purple). Dopamine and serotonin play a role in the regulation of sleep, but the specific subgroups of cells have not been mapped, and thus the major cell groups that produce these transmitters are shown in this figure (black and yellow). PDF-producing large ventral lateral neurons (LNv) are important for promoting arousal in response to light and are shown in blue. Despite not knowing where the neurotransmitter signals originate, areas that receive these signals have been identified (PI neurons or mushroom body). Manipulation of intracellular signaling pathways has also implicated these areas (PI neurons and mushroom body).