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Genetics of Circadian Rhythms and Sleep

Lee, Yin Yeng
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1668637624081914

Abstract Details

2022, PhD, University of Cincinnati, Medicine: Systems Biology and Physiology.
Circadian rhythm is the internal clock that drives daily rhythms and synchronizes the system with external day-night cycle. This clock is a pervasive mechanism that regulates the temporal expression of many genes and controls broad physiology, including sleep. More importantly, mis-regulation of the clock is associated with metabolic disorders, neurodegeneration, sleep-wake disorder, and incidence of cancer. Many works have been done in the past two decades to analyze clock control at the organism level. However, most studies have only characterized genomic profiles of independent condition(s), and mostly in mouse models. Sleep is the most prominent circadian behavior that follows the day-night cycle. Both the quality and duration of sleep can change in the short term and progressively as we age, which has complicated our efforts to understand the genetic contribution to sleep. To this end, little work has been done to use the wealth of genome-wide data available these days to study the genetics of sleep. The goal of this dissertation is to fully utilize the computational power and high throughput sequencing technique to advance the genetic and computational models available for studying the circadian rhythm and sleep. Most circadian studies at the molecular level are limited to mice, mainly due to the rich genetic resources available. To close this gap, we proposed a mapping-by-sequence approach to find causal mutation of a short circadian period in Syrian hamsters. The methods proposed here would be applicable for future mutagenesis studies using hamsters as the genetic model. Additionally, we applied statistical and machine learning models to integrate the large amount of genomic and proteomic profiling studies, to speed up the process of finding key regulators of sleep. Our model uncovers previously unappreciated pathways and genes in sleep regulation. Taken in sum, the work presented in this dissertation showed two use cases on how we can take advantages of the computational and technology available these days to help leverage the research of genetics in circadian rhythm and sleep.
John Hogenesch, Ph.D. (Committee Member)
Ying-Hui Fu, Ph.D. (Committee Member)
Tongli Zhang, Ph.D. (Committee Member)
Leah Claire Kottyan, Ph.D (Committee Member)
Christian Hong, Ph.D. (Committee Member)
107 p.
Genetics
system genetics; circadian rhythm; sleep; machine learning; syrian hamster genome; homozygosity mapping

Recommended Citations

Citations

  • Lee, Y. Y. (2022). Genetics of Circadian Rhythms and Sleep [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1668637624081914

    APA Style (7th edition)

  • Lee, Yin Yeng. Genetics of Circadian Rhythms and Sleep. 2022. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1668637624081914.

    MLA Style (8th edition)

  • Lee, Yin Yeng. "Genetics of Circadian Rhythms and Sleep." Doctoral dissertation, University of Cincinnati, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1668637624081914

    Chicago Manual of Style (17th edition)

ucin1668637624081914
72
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This open access ETD is published by University of Cincinnati and OhioLINK.