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Clock Gene Polymorphisms in Human Subjects with Defined Circadian Phenotypes.

Robilliard, Donna L. (2003) Clock Gene Polymorphisms in Human Subjects with Defined Circadian Phenotypes. Doctoral thesis, University of Surrey (United Kingdom)..

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This work represents part of an investigation testing the hypothesis that polymorphisms in circadian genes are associated with variation in circadian phenotype. Clock was selected as a suitable gene to investigate since previous studies showed that a splice site mutation in mice altered circadian period (tau) and sleep. In humans, a polymorphism had been linked with diurnal preference. By screening genetic databases (Genbank), three potential coding polymorphisms were identified. Two of these (a single nucleotide polymorphism causing substitution of glutamate for a lysine codon (exon 13) and insertion of a glutamine codon (exon 20)) were assessed in: 1) Blind subjects (free running rhythms, previously characterised tau values) 2) Clinically diagnosed delayed sleep phase syndrome patients 3) Control subjects The polymorphisms were not observed in these populations. The third polymorphism identified was a single nucleotide polymorphism that altered the amino acid residue present in exon 14. To assess if novel Clock polymorphisms were associated with variation in tau, regions of Clock were amplified from subject DNA (population 1 above) and sequenced. No polymorphisms were identified suggesting that the variation in tau observed was not linked to polymorphisms in the regions of Clock investigated. Since the Clock gene polymorphism at the 3111 locus in the 3’ untranslated region was reported to be associated with diurnal preference, it was assessed to investigate whether it was associated with tau and/ or delayed sleep phase syndrome. Simultaneously, a functional assay was developed to investigate a possible role for this polymorphism in mRNA stability/translatability. However, no association was observed between this polymorphism and either tau or delayed sleep phase syndrome. In addition, no differences were observed in the functional assay between the two alleles. Finally, this polymorphism was assessed in subjects with extreme diurnal preferences (characterised as part of this thesis). No association was observed suggesting that the conclusions made in the previous investigation were invalid.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Robilliard, Donna L.
Date : 2003
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2003.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:37
Last Modified : 06 May 2020 14:44

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