A Genomic Definition of Centromeres in Complex Genomes
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Centromeres, or sites of chromosomal spindle attachment during mitosis and meiosis, are non-randomly distributed in complex genomes and are largely associated with expansive, near-identical satellite DNA arrays. While the sequence basis of centromere identity remains a subject of considerable debate, one approach is to examine the genomic organization of satellite DNA arrays and their potential function. Current genome assembly and sequence annotation strategies, however, are dependent on robust sequence variation, and, as a result, these regions of near sequence identity remain absent from current genome reference sequences and thus are detached from explorations of centromere biology. This dissertation is designed as a foundational study for centromere genomics, providing the initial steps to characterize those sequences at endogenous centromeres, while further classifying `functional' sequences that directly interact with, or are capable of recruiting proteins involved in, centromere function. These studies build on and take advantage of the limited sequence variation in centromeric satellite DNA, providing the necessary genomic scope to promote biologically meaningful characterization of endogenous centromere sequences in both human and non-human genomes. As a result, this thesis demonstrates possible genomic standards for future studies in the emerging field of satellite biology, which is now positioned to address functional centromere sequence variation across evolutionary time.
DepartmentGenetics and Genomics
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Rights for Collection: Duke Dissertations