<i>CACNA1D</i> is a circadian gene and causes familial advanced sleep phase
Abstract
Familial advanced sleep phase (FASP) is a heritable human sleep trait characterized by early sleep onset and offset times. We have identified five variants in five different families in the human voltage-gated calcium channel subunit alpha1 D ( CACNA1D ) that cosegregate with FASP. The variants in CACNA1D lead to altered channel dynamics in vitro. A mouse model of the E427K variant has a normal circadian period under constant darkness but displays altered phase shifts in response to light in the subjective night at circadian time (CT) 16 and CT22. Overall, these experiments establish CACNA1D as an FASP gene with altered entrainment, highlighting the ability of human genetics to uncover novel aspects of human circadian regulation.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (12)
John M. Webb
Department of Neurology, University of California San Francisco
Fayal Abderemane-Ali
Cardiovascular Research Institute, University of California
Liza Ashbrook
Department of Neurology, University of California San Francisco
Mingyang Ma
Department of Neurology, University of California San Francisco
Neha Nibber
Department of Neurology, University of California San Francisco
Xianlin Zou
Department of Neurology, University of California San Francisco
Maya Yamazaki
Department of Neurology, University of California San Francisco
Elizabeth Wohler
McKusick-Nathans Department of Genetic Medicine, Johns Hopkins Medicine
Nara Sobreira
McKusick-Nathans Department of Genetic Medicine, Johns Hopkins Medicine
Daniel L. Minor
Kavli Institute for Fundamental Neuroscience, University of California San Francisco
Ying-Hui Fu
Department of Neurology, University of California San Francisco
Louis J. Ptáček
Department of Neurology, University of California San Francisco