title: Mutation screening of the human Clock gene in circadian rhythm sleep disorders.
abstract: We tested whether the human Clock (hClock) gene, one of the essential components of the circadian oscillator, is implicated in the vulnerability to delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (N-24). Screening in the entire coding region of the hClock gene with PCR amplification revealed three polymorphisms, of which two predicted the amino acid substitutions R533Q and H542R. The frequencies of the R533Q and H542R alleles in patients with DSPS or N-24 were very low and not significantly different from those in control subjects. A T3111C polymorphism in the 3'-untranslated region of hClock, which had been reportedly associated with morning or evening preference for activity, was also investigated; the results showed that the 3111C allele frequency decreased in DSPS. Polymorphisms in the coding region of the hClock gene are unlikely to play an important role in the development of DSPS or N-24. The possible contribution of the T3111C polymorphism to DSPS susceptibility should be studied further.
authors.affiliation: Department of Neuropsychiatry, Saitama Medical School, 38 Morohongo, Moroyama-cho, Iruma-gun, 350-0495, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Iwase
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kajimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Ebisawa
authors.forename: Kimio
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Kayo
authors.initials: K
authors.lastname: Shibui
authors.forename: Keiko
authors.initials: K
authors.lastname: Kim
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kudo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Katoh
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Toru
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Mariko
authors.initials: M
authors.lastname: Sugishita
authors.forename: Toru
authors.initials: T
authors.lastname: Hori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Toyoshima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mishima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nomura
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Masako
authors.initials: M
authors.lastname: Okawa
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamauchi
mesh_terms: D000328:Adult; D000483:Alleles; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human