Genetic Studies in the Sleep Disorder Narcolepsy

  1. Hiroshi Kadotani1,
  2. Juliette Faraco1, and
  3. Emmanuel Mignot1,2
  1. 1Center for Narcolepsy, Stanford University School of Medicine, Stanford, California 94305 USA

Abstract

Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness and abnormal manifestations of REM sleep including cataplexy, sleep paralysis, and hypnagogic hallucinations. Narcolepsy is both a significant medical problem and a unique disease model for the study of sleep. Research in human narcolepsy has led to the identification of specific HLA alleles (DQB1*0602 andDQA1*0102) that predispose to the disorder. This has suggested the possibility that narcolepsy may be an autoimmune disorder, a hypothesis that has not been confirmed to date. Genetic factors other than HLA are also likely to be involved. In a canine model of narcolepsy, the disorder is transmitted as a non-MHC single autosomal recessive trait with full penetrance (canarc-1). A tightly linked marker for canarc-1 has been identified, and positional cloning studies are under way to isolate canarc-1 from a newly developed canine genomic BAC library. The molecular cloning of this gene may lead to a better understanding of sleep mechanisms, as has been the case for circadian rhythms following the cloning of frq, per, and Clock.

Footnotes

  • 2 Corresponding author.

  • E-MAIL mignot{at}leland.stanford.edu; FAX (650) 498-7761.

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