Title

Searching for the Mammalian Centromere: Excursions in Genome Space

Date of Completion

January 2011

Keywords

Biology, Genetics

Degree

Ph.D.

Abstract

The mammalian centromere is one of the last remaining frontiers in genome sequencing. Characterized by large arrays of highly repetitive DNA, they have proven to be nearly intractable by current sequencing methods. This absolutely critical genomic structure is required for accurate division of replicated DNA during cell division. While the proteins underlying a functional centromere are well defined within most eukaryotes, no common DNA sequence has yet been found that determines where a centromere is formed. The work contained in this thesis is an exploration of the mammalian genome in search of that ever-elusive DNA sequence that denotes centromere identity and/or potential. The results identify particular retrotransposable elements as features common to active centromeres and regions of potential centromeres within marsupials. Centromere identity has also been linked to small RNAs. As such, a detailed examination of a novel class of small RNAs in primates demonstrates the class to be well conserved and originating from a newly discovered transposable element class, SINE28. The presented data provides correlational evidence which suggests these RNAs are an underlying functional component of mammalian centromeres. ^