Mackiewicz M, Paigen B, Naidoo N, Pack A I
Department of Medicine, Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA 19104-3403, USA.
Physiol Genomics. 2008 Mar 14;33(1):91-9. doi: 10.1152/physiolgenomics.00189.2007. Epub 2008 Jan 2.
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.
0.5 - 4赫兹频率范围内的脑电图振荡是慢波睡眠（SWS）的特征，通常被称为δ振荡或δ功率。δ功率反映睡眠强度，并与对睡眠剥夺的稳态反应相关。一项已发表的对近交系小鼠的调查表明，δ功率积累的时间进程在近交系之间有所不同，并且在BxD重组近交系中δ功率反弹的分离确定了13号染色体上一个称为慢波睡眠中δ功率（或Dps1）的基因组区域。数量性状基因座（QTL）包含在睡眠剥夺后修饰δ功率积累的基因。在这里，我们使用区间特异性单倍型分析缩小了QTL范围，并通过序列比较对Dps1区域中剩余的基因进行了全面注释，以识别编码区和调控区内的多态性。我们确定了位于B6和D2亲本菌株睡眠和清醒状态下Dps1区间内选定基因的表达模式。综合起来，这些步骤减少了睡眠剥夺后可能是δ功率积累基础并解释Dps1 QTL的潜在候选基因数量。最强的候选基因是Homer1a，其得到睡眠和清醒状态之间表达差异以及上游调控区域中SNP多态性的支持。
