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 pro bably by gene-environment interactions. Among different approaches to the g enetics of sleep, analysis of quantitative traits (QTL) has the advantage o f being able to detect, along with major genes, minor and/or modifier genes influencing different quantitative aspects of sleep. We have used QTL anal ysis in two different sets of recombinant inbred (RI) strains and sought fo r confirmation of several localizations in eight histocompatibility congeni c strains. Several QTLs were identified which influenced the amount of vigi lance 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 t otal sleep. Among these, a single QTL on chromosome 5 was associated with a ll vigilance stales, suggesting the presence of a major gene influencing a basic aspect of sleep amount. Search for candidate genes around the identif ied QTLs indicated several immune related genes that have been implicated i n sleep regulation. Transgenic animals carrying loss-of-function and/or gai n-of-function mutations affecting these candidate genes should confirm thes e findings.