Genetic Analysis of Daily Activity in Humans and Mice
Abstract
Virtually all organisms express circadian oscillations of physiology, biochemistry, or behavior that reflect their need to anticipate the 24 hour periodicity of night and day. Genetic heterogeneity underlies many phenotypic variations observed in circadian rhythmicity. In order to identify genetic loci that underlie this complex behavior, we have carried out a genome-wide complex trait analysis in (C57BL/6J x BALB/cJ)F2 hybrid mice. We have characterized variation in five circadian phenotypes: free-running circadian period, phase angle of entrainment, amplitude of the circadian rhythm, circadian activity level, and dissociation of rhythmicity. Quantitative trait locus analysis of these phenotypes has led to the identification of 13 loci having significant effects on this behavior. Although single gene mutations can affect circadian rhythms, the analysis of interstrain variants demonstrates that significant genetic complexity underlies this behavior. Importantly, the large majority of the loci that we have detected by these methods map to locations that differ from the nine known clock genes, indicating the presence of additional clock-relevant genes in the mammalian circadian system. These data demonstrate the analytical value of quantitative trait locus analysis in understanding complex phenotypes, and point to promising approaches for genetic analysis of such phenotypes in other mammals, including humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 30, 1999
- Accession Number
- ADA387567
Entities
People
- Joseph S. Takahashi
Organizations
- Northwestern University