期刊
SLEEP
卷 37, 期 8, 页码 1327-U127出版社
OXFORD UNIV PRESS INC
DOI: 10.5665/sleep.3924
关键词
BHLHE41; delta power; genetics; sleep; sleep deprivation; sleep loss
资金
- NIH [P01 HL094307, NR004281]
- Institutional Development Fund from the Center for Applied Genomics at The Children's Hospital of Philadelphia
- National Space Biomedical Research Institute through NASA [NCC 9-58]
- CTRC [UL1RR024134]
- Department of the Navy, Office of Naval Research [N00014-11-1-0361]
- Pulsar Informatics
- Boeing Company
- Battelle Center for Human Performance Safety
- Institutes for Behavior Resources
- FedEx Express
Study Objectives: Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loop-helix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Design: Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. Results: We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. Conclusions: There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据