Analysis of the QTL for sleep homeostasis in mice: Homer1a is a likely candidate

• Published in: Physiological genomics Vol. 33; no. 1; pp. 91 - 99
• Main Authors: Mackiewicz, M, Paigen, B, Naidoo, N, Pack, A. I
• Format: Journal Article
• Language: English
• Published: United States Am Physiological Soc 14-03-2008
• Subjects: Algorithms; Animals; Base Sequence; Carrier Proteins - genetics; Carrier Proteins - physiology; Chromosome Mapping; Computational Biology; DNA Mutational Analysis; Haplotypes; Homeostasis - genetics; Homer Scaffolding Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Molecular Sequence Data; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Regulatory Sequences, Nucleic Acid; Sequence Homology, Nucleic Acid; Sleep - genetics; Sleep Deprivation - genetics; Wakefulness - genetics
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00189.2007

1 Division of Sleep Medicine/Department of Medicine and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, Pennsylvania
2 The Jackson Laboratory, Bar Harbor, Maine
Electroencephalographic oscillations in the frequency range of 0.5–4 Hz, characteristic of slow-wave sleep (SWS), are often referred to as the delta oscillation or delta power. Delta power reflects sleep intensity and correlates with the homeostatic response to sleep loss. A published survey of inbred strains of mice demonstrated that the time course of accumulation of delta power varied among inbred strains, and the segregation of the rebound of delta power in BxD recombinant inbred strains identified a genomic region on chromosome 13 referred to as the delta power in SWS (or Dps1 ). The quantitative trait locus (QTL) contains genes that modify the accumulation of delta power after sleep deprivation. Here, we narrow the QTL using interval-specific haplotype analysis and present a comprehensive annotation of the remaining genes in the Dps1 region with sequence comparisons to identify polymorphisms within the coding and regulatory regions. We established the expression pattern of selected genes located in the Dps1 interval in sleep and wakefulness in B6 and D2 parental strains. Taken together, these steps reduced the number of potential candidate genes that may underlie the accumulation of delta power after sleep deprivation and explain the Dps1 QTL. The strongest candidate gene is Homer1a , which is supported by expression differences between sleep and wakefulness and the SNP polymorphism in the upstream regulatory regions.
Homer1a ; sleep; quantitative trait locus; haplotype; gene expression