Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice.

Sleep is a complex trait controlled by many genes, the environment, and probably by gene-environment interactions. Among different approaches to the genetics of sleep, analysis of quantitative traits (QTL) has the advantage of being able to detect, along with major genes, minor and/or modifier genes influencing different quantitative aspects of sleep. We have used QTL analysis in two different sets of recombinant inbred (RI) strains and sought for confirmation of several localizations in eight histocompatibility congenic strains. Several QTLs were identified which influenced the amount of vigilance states. In a first RI series (seven strains) the only QTLs identified were those affecting paradoxical sleep (PS), whereas analysis in a second RI series (25 strains) revealed QTLs influencing PS, slow-wave sleep, and total sleep. Among these, a single QTL on chromosome 5 was associated with all vigilance states, suggesting the presence of a major gene influencing a basic aspect of sleep amount. Search for candidate genes around the identified QTLs indicated several immune related genes that have been implicated in sleep regulation. Transgenic animals carrying loss-of-function and/or gain-of-function mutations affecting these candidate genes should confirm these findings.