Diversity of Human Clock Genotypes and Consequences - Progress in Molecular Biology and Translational Science - page 51

CHAPTER THREE

Diversity of Human Clock
Genotypes and Consequences

Luoying Zhang * , Louis J. Ptá č ek * , † , Ying-Hui Fu *
* Department of Neurology, University of California, San Francisco, California, USA
† Howard Hughes Medical Institute, University of California, San Francisco, California, USA

Contents
1. Introduction 52

2. BMAL1 53

3. CLOCK 54

4. NPAS2 57

5. PER1 58

6. PER2 58

7. PER3 62

8. CRY1 64

9. CRY2 64

10. REV-ERBa 65

11. CK1e 65

12. CK1d 66

13. CUL1 67

14. b-TrCP 67

15. DEC1 68

16. DEC2 68

17. TIMELESS 70

18. Concluding Remarks 70

References 74

Abstract
The molecular clock consists of a number of genes that form transcriptional and post-
transcriptional feedback loops, which function together to generate circadian oscilla-
tions that give rise to circadian rhythms of our behavioral and physiological
processes. Genetic variations in these clock genes have been shown to be associated
with phenotypic effects in a repertoire of biological processes, such as diurnal prefer-
ence, sleep, metabolism, mood regulation, addiction, and fertility. Consistently, rodent
models carrying mutations in clock genes also demonstrate similar phenotypes. Taken
together, these studies suggest that human clock-gene variants contribute to the phe-
notypic differences observed in various behavioral and physiological processes,