Mutation of the human circadian clock gene CRY1 in familial delayed sleep phase disorder

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dc.citation.epage215en_US
dc.citation.issueNumber2en_US
dc.citation.spage203en_US
dc.citation.volumeNumber169en_US
dc.contributor.authorPatke, A.en_US
dc.contributor.authorMurphy, P. J.en_US
dc.contributor.authorOnat, O. E.en_US
dc.contributor.authorKrieger, A. C.en_US
dc.contributor.authorÖzçelik, T.en_US
dc.contributor.authorCampbell, S. S.en_US
dc.contributor.authorYoung, M. W.en_US
dc.date.accessioned2018-04-12T11:13:07Z
dc.date.available2018-04-12T11:13:07Z
dc.date.issued2017en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractPatterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1. This gain-of-function CRY1 variant causes reduced expression of key transcriptional targets and lengthens the period of circadian molecular rhythms, providing a mechanistic link to DSPD symptoms. The allele has a frequency of up to 0.6%, and reverse phenotyping of unrelated families corroborates late and/or fragmented sleep patterns in carriers, suggesting that it affects sleep behavior in a sizeable portion of the human population. © 2017 Elsevier Inc.en_US
dc.identifier.doi10.1016/j.cell.2017.03.027en_US
dc.identifier.issn0092-8674
dc.identifier.urihttp://hdl.handle.net/11693/37425
dc.language.isoEnglishen_US
dc.publisherCell Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2017.03.027en_US
dc.source.titleCellen_US
dc.subjectCircadian clocken_US
dc.subjectCircadian rhythmen_US
dc.subjectDSPDen_US
dc.subjectSleepen_US
dc.subjectComplementary DNAen_US
dc.subjectCryptochrome 1en_US
dc.subjectMelatoninen_US
dc.subjectMessenger RNAen_US
dc.subjectTranscription factor ARNTLen_US
dc.subjectTranscription factor CLOCKen_US
dc.titleMutation of the human circadian clock gene CRY1 in familial delayed sleep phase disorderen_US
dc.typeArticleen_US

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